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Sample records for human chondrosarcoma cells

  1. Intrinsic radiation resistance in human chondrosarcoma cells

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    Moussavi-Harami, Farid; Mollano, Anthony; Martin, James A.; Ayoob, Andrew; Domann, Frederick E.; Gitelis, Steven; Buckwalter, Joseph A.

    2006-01-01

    Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death. However, cells that lack cell cycle control mechanisms needed for these responses show intrinsic radiation resistance. In previous work, we identified immortalized human chondrosarcoma cell lines that lacked p16 ink4a , one of the major tumor suppressor proteins that regulate the cell cycle. We hypothesized that the absence of p16 ink4a contributes to the intrinsic radiation resistance of chondrosarcomas and that restoring p16 ink4a expression would increase their radiation sensitivity. To test this we determined the effects of ectopic p16 ink4a expression on chondrosarcoma cell resistance to low-dose γ-irradiation (1-5 Gy). p16 ink4a expression significantly increased radiation sensitivity in clonogenic assays. Apoptosis did not increase significantly with radiation and was unaffected by p16 ink4a transduction of chondrosarcoma cells, indicating that mitotic catastrophe, rather than programmed cell death, was the predominant radiation effect. These results support the hypothesis that p16 ink4a plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas

  2. The antiapoptotic gene survivin is highly expressed in human chondrosarcoma and promotes drug resistance in chondrosarcoma cells in vitro

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    2011-01-01

    Background Chondrosarcoma is virtually resistant to chemotherapy and radiation therapy. Survivin, the smallest member of the inhibitor of apoptosis protein family, is a critical factor for tumor progression and resistance to conventional therapeutic approaches in a wide range of malignancies. However, the role of survivin in chondrosarcoma has not been well studied. We examined the importance of survivin gene expression in chondrosarcoma and analysed its influences on proliferation, apoptosis and resistance to chemotherapy in vitro. Methods Resected chondrosarcoma specimens from which paraffin-embedded tissues could be extracted were available from 12 patients. In vitro experiments were performed in human chondrosarcoma cell lines SW1353 and Hs819.T. Immunohistochemistry, immunoblot, quantitative PCR, RNA interference, gene-overexpression and analyses of cell proliferation and apoptosis were performed. Results Expression of survivin protein was detected in all chondrosarcoma specimens analyzed, while undetectable in adult human cartilage. RNA interference targeting survivin resulted in a G2/M-arrest of the cell cycle and led to increased rates of apoptosis in chondrosarcoma cells in vitro. Overexpression of survivin resulted in pronounced resistance to doxorubicin treatment. Conclusions These findings indicate that survivin plays a role in the pathogenesis and pronounced chemoresistance of high grade chondrosarcoma. Survivin antagonizing therapeutic strategies may lead to new treatment options in unresectable and metastasized chondrosarcoma. PMID:21457573

  3. The antiapoptotic gene survivin is highly expressed in human chondrosarcoma and promotes drug resistance in chondrosarcoma cells in vitro

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    Lechler, Philipp; Renkawitz, Tobias; Campean, Valentina; Balakrishnan, Sanjeevi; Tingart, Markus; Grifka, Joachim; Schaumburger, Jens

    2011-01-01

    Chondrosarcoma is virtually resistant to chemotherapy and radiation therapy. Survivin, the smallest member of the inhibitor of apoptosis protein family, is a critical factor for tumor progression and resistance to conventional therapeutic approaches in a wide range of malignancies. However, the role of survivin in chondrosarcoma has not been well studied. We examined the importance of survivin gene expression in chondrosarcoma and analysed its influences on proliferation, apoptosis and resistance to chemotherapy in vitro. Resected chondrosarcoma specimens from which paraffin-embedded tissues could be extracted were available from 12 patients. In vitro experiments were performed in human chondrosarcoma cell lines SW1353 and Hs819.T. Immunohistochemistry, immunoblot, quantitative PCR, RNA interference, gene-overexpression and analyses of cell proliferation and apoptosis were performed. Expression of survivin protein was detected in all chondrosarcoma specimens analyzed, while undetectable in adult human cartilage. RNA interference targeting survivin resulted in a G 2 /M-arrest of the cell cycle and led to increased rates of apoptosis in chondrosarcoma cells in vitro. Overexpression of survivin resulted in pronounced resistance to doxorubicin treatment. These findings indicate that survivin plays a role in the pathogenesis and pronounced chemoresistance of high grade chondrosarcoma. Survivin antagonizing therapeutic strategies may lead to new treatment options in unresectable and metastasized chondrosarcoma

  4. The antiapoptotic gene survivin is highly expressed in human chondrosarcoma and promotes drug resistance in chondrosarcoma cells in vitro

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    Grifka Joachim

    2011-04-01

    Full Text Available Abstract Background Chondrosarcoma is virtually resistant to chemotherapy and radiation therapy. Survivin, the smallest member of the inhibitor of apoptosis protein family, is a critical factor for tumor progression and resistance to conventional therapeutic approaches in a wide range of malignancies. However, the role of survivin in chondrosarcoma has not been well studied. We examined the importance of survivin gene expression in chondrosarcoma and analysed its influences on proliferation, apoptosis and resistance to chemotherapy in vitro. Methods Resected chondrosarcoma specimens from which paraffin-embedded tissues could be extracted were available from 12 patients. In vitro experiments were performed in human chondrosarcoma cell lines SW1353 and Hs819.T. Immunohistochemistry, immunoblot, quantitative PCR, RNA interference, gene-overexpression and analyses of cell proliferation and apoptosis were performed. Results Expression of survivin protein was detected in all chondrosarcoma specimens analyzed, while undetectable in adult human cartilage. RNA interference targeting survivin resulted in a G2/M-arrest of the cell cycle and led to increased rates of apoptosis in chondrosarcoma cells in vitro. Overexpression of survivin resulted in pronounced resistance to doxorubicin treatment. Conclusions These findings indicate that survivin plays a role in the pathogenesis and pronounced chemoresistance of high grade chondrosarcoma. Survivin antagonizing therapeutic strategies may lead to new treatment options in unresectable and metastasized chondrosarcoma.

  5. ADAMTS13 expression in human chondrosarcoma cells induced by insulin

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    Rıdvan Fırat

    2014-06-01

    Full Text Available Objectives: A Disintegrin-like Metalloproteinase with Thrombospondin Motifs (ADAMTS proteins is a proteinase enzyme group that primarily located in the extracellular matrix (ECM. Insulin has been known to stimulate proteoglycan biosynthesis in chondrosarcoma chondrocytes and thereby the levels of ADAMTS proteins. The aim of this study is to evaluate the time-dependent effects of insulin on the ADAMTS13 expression in OUMS-27 human chondrosarcoma cell line to test the hypothesis that insulin diminishes ADAMTS13 expression because of its anabolic effects. Methods: To test this hypothesis OUMS-27 cells were cultured in Dulbecco’s modified Eagle’ medium (DMEM containing 10μg/mL insulin. The medium containing insulin was changed every other day up to 11th day. Cells were harvested at 1, 3, 7, and 11th days and protein and RNA isolations were performed at the proper times. The levels of RNA expression of ADAMTS13 was quantified by qRT-PCR using appropriate primers while protein levels was detected by Western blot technique using anti-ADAMTS13 antibody. Results: Although there was a decrease in both RNA and protein levels in insulin-applied groups compared to the control cells, it was not statistically significant. Conclusion: Under the light of our findings, it is suggested that insulin does not participate in regulation of ADAMTS13 in OUMS-27 chondrosarcoma cells. J Clin Exp Invest 2014; 5 (2: 226-232

  6. Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

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    Su, Chen-Ming; Wang, Shih-Wei; Lee, Tzong-Huei; Tzeng, Wen-Pei; Hsiao, Che-Jen; Liu, Shih-Chia; Tang, Chih-Hsin

    2013-01-01

    Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: • Trichodermin induces chondrosarcoma apoptosis. • ER stress is involved in trichodermin-induced cell death. • Trichodermin induces chondrosarcoma death in vivo.

  7. Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

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    Su, Chen-Ming [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Wang, Shih-Wei [Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (China); Lee, Tzong-Huei [Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan (China); Tzeng, Wen-Pei [Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan (China); Hsiao, Che-Jen [School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Liu, Shih-Chia [Department of Orthopaedics, Mackay Memorial Hospital, Taipei, Taiwan (China); Tang, Chih-Hsin, E-mail: chtang@mail.cmu.edu.tw [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan (China)

    2013-10-15

    Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: • Trichodermin induces chondrosarcoma apoptosis. • ER stress is involved in trichodermin-induced cell death. • Trichodermin induces chondrosarcoma death in vivo.

  8. Rapamycin causes growth arrest and inhibition of invasion in human chondrosarcoma cells.

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    Song, Jian; Wang, Xiaobo; Zhu, Jiaxue; Liu, Jun

    2016-01-01

    Chondrosarcoma is a highly malignant tumor that is characterized by a potent capacity to invade locally and cause distant metastasis and notable for its lack of response to conventional chemotherapy or radiotherapy. Rapamycin, the inhibitor of mammalian target of rapamycin (mTOR), is a valuable drug with diverse clinical applications and regulates many cellular processes. However, the effects of rapamycin on cell growth and invasion of human chondrosarcoma cells are not well known. We determined the effect of rapamycin on cell proliferation, cell cycle arrest and invasion by using MTS, flow cytometry and invasion assays in two human chondrosarcoma cell lines, SW1353 and JJ012. Cell cycle regulatory and invasion-related genes' expression analysis was performed by quantitative RT-PCR (qRT-PCR). We also evaluated the effect of rapamycin on tumor growth by using mice xenograph models. Rapamycin significantly inhibited the cell proliferation, induced cell cycle arrest and decreased the invasion ability of human chondrosarcoma cells. Meanwhile, rapamycin modulated the cell cycle regulatory and invasion-related genes' expression. Furthermore, the tumor growth of mice xenograph models with human chondrosarcoma cells was significantly inhibited by rapamycin. These results provided further insight into the role of rapamycin in chondrosarcoma. Therefore, rapamycin targeted therapy may be a potential treatment strategy for chondrosarcoma.

  9. HGF and c-Met Interaction Promotes Migration in Human Chondrosarcoma Cells

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    Tsou, Hsi-Kai; Chen, Hsien-Te; Hung, Ya-Huey; Chang, Chia-Hao; Li, Te-Mao; Fong, Yi-Chin; Tang, Chih-Hsin

    2013-01-01

    Chondrosarcoma is a type of highly malignant tumor with a potent capacity for local invasion and causing distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Hepatocyte growth factor (HGF) has been demonstrated to stimulate cancer proliferation, migration, and metastasis. However, the effect of HGF on migration activity of human chondrosarcoma cells is not well known. Here, we found that human chondrosarcoma tissues demonstrated significant expression of HGF, which was higher than that in normal cartilage. We also found that HGF increased the migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. c-Met inhibitor and siRNA reduced HGF-increased cell migration and MMP-2 expression. HGF treatment resulted in activation of the phosphatidylinositol 3′-kinase (PI3K)/Akt/PKCδ/NF-κB pathway, and HGF-induced expression of MMP-2 and cell migration was inhibited by specific inhibitors or siRNA-knockdown of PI3K, Akt, PKCδ, and NF-κB cascades. Taken together, our results indicated that HGF enhances migration of chondrosarcoma cells by increasing MMP-2 expression through the c-Met receptor/PI3K/Akt/PKCδ/NF-κB signal transduction pathway. PMID:23320110

  10. HGF and c-Met interaction promotes migration in human chondrosarcoma cells.

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    Hsi-Kai Tsou

    Full Text Available Chondrosarcoma is a type of highly malignant tumor with a potent capacity for local invasion and causing distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Hepatocyte growth factor (HGF has been demonstrated to stimulate cancer proliferation, migration, and metastasis. However, the effect of HGF on migration activity of human chondrosarcoma cells is not well known. Here, we found that human chondrosarcoma tissues demonstrated significant expression of HGF, which was higher than that in normal cartilage. We also found that HGF increased the migration and expression of matrix metalloproteinase (MMP-2 in human chondrosarcoma cells. c-Met inhibitor and siRNA reduced HGF-increased cell migration and MMP-2 expression. HGF treatment resulted in activation of the phosphatidylinositol 3'-kinase (PI3K/Akt/PKCδ/NF-κB pathway, and HGF-induced expression of MMP-2 and cell migration was inhibited by specific inhibitors or siRNA-knockdown of PI3K, Akt, PKCδ, and NF-κB cascades. Taken together, our results indicated that HGF enhances migration of chondrosarcoma cells by increasing MMP-2 expression through the c-Met receptor/PI3K/Akt/PKCδ/NF-κB signal transduction pathway.

  11. The Investigation of ADAMTS16 in Insulin-Induced Human Chondrosarcoma Cells.

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    Cakmak, Ozlem; Comertoglu, Ismail; Firat, Ridvan; Erdemli, Haci Kemal; Kursunlu, S Fatih; Akyol, Sumeyya; Ugurcu, Veli; Altuntas, Aynur; Adam, Bahattin; Demircan, Kadir

    2015-08-01

    A disintegrin-like metalloproteinase with thrombospondin motifs (ADAMTS) is a group of proteins that have enzymatic activity secreted by cells to the outside extracellular matrix. Insulin induces proteoglycan biosynthesis in chondrosarcoma chondrocytes. The purpose of the present in vitro study is to assess the time course effects of insulin on ADAMTS16 expression in OUMS-27 (human chondrosarcoma) cell line to examine whether insulin regulates ADAMTS16 expression as well as proteoglycan biosynthesis with multifaceted properties or not. Chondrosarcoma cells were cultured in Dulbecco's modified Eagle's medium having either 10 μg/mL insulin or not. While the experiment was going on, the medium containing insulin had been changed every other day. Cells were harvested at 1st, 3rd, 7th, and 11th days; subsequently, RNA and proteins were isolated in every experimental group according to their time interval. RNA expression of ADAMTS was estimated by quantitative real-time polymerase chain reaction (qRT-PCR) by using primers. Immunoreactive protein levels were encountered by the western blot protein detection technique by using proper anti-ADAMTS16 antibodies. ADAMTS16 mRNA expression level of chondrosarcoma cells was found to be insignificantly decreased in chondrosarcoma cells induced by insulin detected by the qRT-PCR instrument. On the other hand, there was a gradual decrease in immune-reactant ADAMTS16 protein amount by the time course in insulin-treated cell groups when compared with control cells. It has been suggested that insulin might possibly regulate ADAMTS16 levels/activities in OUMS-27 chondrosarcoma cells taking a role in extracellular matrix turnover.

  12. BMPR2 inhibition induced apoptosis and autophagy via destabilization of XIAP in human chondrosarcoma cells

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    Jiao, G; Guo, W; Ren, T; Lu, Q; Sun, Y; Liang, W; Ren, C; Yang, K; Sun, K

    2014-01-01

    Bone morphogenetic proteins (BMPs) are multifunctional proteins, and their receptors (BMPRs) have crucial roles in the process of signaling. However, their function in cancer is somewhat inconsistent. It has been demonstrated that more prevalent expression of bone morphogenetic protein receptor 2 (BMPR2) has been detected in dedifferentiated chondrosarcomas than conventional chondrosarcomas. Here, we find that BMPR2 inhibition induces apoptosis and autophagy of chondrosarcoma. We found that BMPR2 expression was correlated with the clinicopathological features of chondrosarcomas, and could predict the treatment outcome. Knockdown of BMPR2 by small interfering RNA results in growth inhibition in chondrosarcoma cells. Silencing BMPR2 promoted G2/M cell cycle arrest, induced chondrosarcoma cell apoptosis through caspase-3-dependent pathway via repression of X-linked inhibitor of apoptosis protein (XIAP) and induced autophagy of chondrosarcoma cells via XIAP-Mdm2-p53 pathway. Inhibition of autophagy induced by BMPR2 small interfering RNA (siBMPR2) sensitized chondrosarcoma cells to siBMPR2-induced apoptotic cell death, suggesting that autophagy has a protective role for chondrosarcoma cells in context of siBMPR2-induced apoptotic cell death. In vivo tumorigenicity assay in mice indicated that inhibition of BMPR2 reduced tumor growth. Taken together, our results suggest that BMPR2 has a significant role in the tumorigenesis of chondrosarcoma, and could be an important prognostic marker for chondrosarcoma. BMPR2 inhibition could eventually provide a promising therapy for chondrosarcoma treatment. PMID:25501832

  13. Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells.

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    Zeng, Wei; Xiao, Tao; Cai, Anlie; Cai, Weiliang; Liu, Huanhuan; Liu, Jingling; Li, Jie; Tan, Miduo; Xie, Li; Liu, Ying; Yang, Xiangcheng; Long, Yi

    2017-01-01

    Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear. We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy. We show that salidroside induced significant apoptosis in the human chondrosarcoma cell line SW1353. In addition, we demonstrate that salidroside-induced an autophagic response in SW1353 cells, as evidenced by the upregulation of LC3-II and downregulation of P62. Moreover, pharmacological or genetic blocking of autophagy enhanced salidroside -induced apoptosis, indicating the cytoprotective role of autophagy in salidroside-treated SW1353 cells. Salidroside also induced TFEB (Ser142) dephosphorylation, subsequently to activated TFEB nuclear translocation and increase of TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes. Importantly, we found that salidroside triggered the generation of ROS in SW1353 cells. Furthermore, NAC, a ROS scavenger, abrogated the effects of salidroside on TFEB-dependent autophagy. These data demonstrate that salidroside increased TFEB-dependent autophagy by activating ROS signaling pathways in human chondrosarcoma cells. These data also suggest that blocking ROS-TFEB-dependent autophagy to enhance the activity of salidroside warrants further attention in treatment of human chondrosarcoma cells. © 2017 The Author(s). Published by S. Karger AG, Basel.

  14. Resistin facilitates VEGF-C-associated lymphangiogenesis by inhibiting miR-186 in human chondrosarcoma cells.

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    Su, Chen-Ming; Tang, Chih-Hsin; Chi, Meng-Ju; Lin, Chih-Yang; Fong, Yi-Chin; Liu, Yueh-Ching; Chen, Wei-Cheng; Wang, Shih-Wei

    2018-05-03

    Chondrosarcoma is a common primary malignant tumor of the bone that can metastasize through the vascular system to other organs. A key step in the metastatic process, lymphangiogenesis, involves vascular endothelial growth factor-C (VEGF-C). However, the effects of lymphangiogenesis in chondrosarcoma metastasis remain to be clarified. Accumulating evidence shows that resistin, a cytokine secreted from adipocytes and monocytes, also promotes tumor pathogenesis. Notably, chondrosarcoma can easily metastasize. In this study, we demonstrate that resistin enhances VEGF-C expression and lymphatic endothelial cells (LECs)-associated lymphangiogenesis in human chondrosarcoma cells. We also show that resistin triggers VEGF-C-dependent lymphangiogenesis via the c-Src signaling pathway and down-regulating micro RNA (miR)-186. Overexpression of resistin in chondrosarcoma cells significantly enhanced VEGF-C production and LECs-associated lymphangiogenesis in vitro and tumor-related lymphangiogenesis in vivo. Resistin levels were positively correlated with VEGF-C-dependent lymphangiogenesis via the down-regulation of miR-186 expression in clinical samples from chondrosarcoma tissue. This study is the first to evaluate the mechanism underlying resistin-induced promotion of LECs-associated lymphangiogenesis via the upregulation of VEGF-C expression in human chondrosarcomas. We suggest that resistin may represent a molecular target in VEGF-C-associated tumor lymphangiogenesis in chondrosarcoma metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Clear cell chondrosarcoma

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    Kumar, R.; David, R.; Cierney, G. III

    1985-01-01

    The clinical, radiologic, and histopathologic features of three cases of clear cell chondrosarcoma are described. On radiographs, this rather benign-appearing tumor resembles a chondroblastoma when it occurs at the end of a long bone, and may occasionally show a calcified matrix. However, it has distinctive tumor cells with a centrally placed vesicular nucleus surrounded by clear cytoplasm. The lesion has a low-grade malignancy and is amenable to en bloc surgical resection, which results in a much better prognosis than that of conventional chondrosarcoma.

  16. CCL5 promotes VEGF-C production and induces lymphangiogenesis by suppressing miR-507 in human chondrosarcoma cells.

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    Wang, Li-Hong; Lin, Chih-Yang; Liu, Shih-Chia; Liu, Guan-Ting; Chen, Yen-Ling; Chen, Jih-Jung; Chan, Chia-Han; Lin, Ting-Yi; Chen, Chi-Kuan; Xu, Guo-Hong; Chen, Shiou-Sheng; Tang, Chih-Hsin; Wang, Shih-Wei

    2016-06-14

    Chondrosarcoma is the second most frequently occurring type of bone malignancy that is characterized by the distant metastasis propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumor lymphangiogenesis and lymphatic metastasis. Chemokine CCL5 has been reported to facilitate angiogenesis and metastasis in chondrosarcoma. However, the effect of chemokine CCL5 on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has largely remained a mystery. In this study, we showed a clinical correlation between CCL5 and VEGF-C as well as tumor stage in human chondrosarcoma tissues. We further demonstrated that CCL5 promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium (CM) from CCL5-overexpressed cells significantly induced tube formation of human lymphatic endothelial cells (LECs). Mechanistic investigations showed that CCL5 activated VEGF-C-dependent lymphangiogenesis by down-regulating miR-507. Moreover, inhibiting CCL5 dramatically reduced VEGF-C and lymphangiogenesis in the chondrosarcoma xenograft animal model. Collectively, we document for the first time that CCL5 induces tumor lymphangiogenesis by the induction of VEGF-C in human cancer cells. Our present study reveals miR-507/VEGF-C signaling as a novel mechanism in CCL5-mediated tumor lymphangiogenesis. Targeting both CCL5 and VEGF-C pathways might serve as the potential therapeutic strategy to block cancer progression and metastasis in chondrosarcoma.

  17. Leptin promotes VEGF-C production and induces lymphangiogenesis by suppressing miR-27b in human chondrosarcoma cells.

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    Yang, Wei-Hung; Chang, An-Chen; Wang, Shih-Wei; Wang, Shoou-Jyi; Chang, Yung-Sen; Chang, Tzu-Ming; Hsu, Shao-Keh; Fong, Yi-Chin; Tang, Chih-Hsin

    2016-06-27

    Chondrosarcoma is the second most frequently occurring type of bone malignancy that is characterized by the distant metastasis propensity. Vascular endothelial growth factor-C (VEGF-C) is the chief lymphangiogenic mediator, and makes crucial contributions to tumor lymphangiogenesis. Leptin is an adipocytokine and has been indicated to facilitate tumorigenesis, angiogenesis and metastasis. However, the effect of leptin on VEGF-C regulation and lymphangiogenesis in human chondrosarcoma has hugely remained a mystery. Our results showed a clinical correlation between leptin and VEGF-C as well as tumor stage in human chondrosarcoma tissues. We further demonstrated that leptin promoted VEGF-C production and secretion in human chondrosarcoma cells. The conditioned medium from leptin-treated chondrosarcoma cells induced lymphangiogenesis of human lymphatic endothelial cells. We also found that leptin-induced VEGF-C is mediated by the FAK, PI3K and Akt signaling pathway. Furthermore, the expression of microRNA-27b was negatively regulated by leptin via the FAK, PI3K and Akt cascade. Our study is the first to describe the mechanism of leptin-promoted lymphangiogenesis by upregulating VEGF-C expression in chondrosarcomas. Thus, leptin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis.

  18. β5 Integrin Up-Regulation in Brain-Derived Neurotrophic Factor Promotes Cell Motility in Human Chondrosarcoma

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    Li, Te-Mao; Fong, Yi-Chin; Liu, Shan-Chi; Chen, Po-Chun; Tang, Chih-Hsin

    2013-01-01

    Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis; it has a poor prognosis and shows a predilection for metastasis to the lungs. Brain derived neurotrophic factor (BDNF) is a small-molecule protein from the neurotrophin family of growth factors that is associated with the disease status and outcomes of cancers. However, the effect of BDNF on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma tissues showed significant expression of BDNF, which was higher than that in normal cartilage and primary chondrocytes. We also found that BDNF increased the migration and expression of β5 integrin in human chondrosarcoma cells. In addition, knockdown of BDNF expression markedly inhibited migratory activity. BDNF-mediated migration and β5 integrin up-regulation were attenuated by antibody, inhibitor, or siRNA against the TrkB receptor. Pretreatment of chondrosarcoma cells with PI3K, Akt, and NF-κB inhibitors or mutants also abolished BDNF-promoted migration and integrin expression. The PI3K, Akt, and NF-κB signaling pathway was activated after BDNF treatment. Taken together, our results indicate that BDNF enhances the migration of chondrosarcoma by increasing β5 integrin expression through a signal transduction pathway that involves the TrkB receptor, PI3K, Akt, and NF-κB. BDNF thus represents a promising new target for treating chondrosarcoma metastasis. PMID:23874483

  19. A novel benzofuran derivative, ACDB, induces apoptosis of human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress.

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    Su, Chen-Ming; Chen, Chien-Yu; Lu, Tingting; Sun, Yi; Li, Weimin; Huang, Yuan-Li; Tsai, Chun-Hao; Chang, Chih-Shiang; Tang, Chih-Hsin

    2016-12-13

    Chondrosarcoma is one of the bone tumor with high mortality in respond to poor radiation and chemotherapy treatment. Here, we analyze the antitumor activity of a novel benzofuran derivative, 2-amino-3-(2-chlorophenyl)-6-(4-dimethylaminophenyl)benzofuran-4-yl acetate (ACDB), in human chondrosarcoma cells. ACDB increased the cell apoptosis of human chondrosarcomas without harm in chondrocytes. ACDB also enhanced endoplasmic reticulum (ER) stress, which was characterized by varieties in the cytosolic calcium levels and induced the expression of glucose-regulated protein (GRP) and calpain. Furthermore, the ACDB-induced chondrosarcoma apoptosis was associated with the upregulation of the B cell lymphoma-2 (Bcl-2) family members including pro- and anti-apoptotic proteins, downregulation of dysfunctional mitochondria that released cytochrome C, and subsequent activation of caspases-3. In addition, the ACDB-mediated cellular apoptosis was suppressed by transfecting cells with glucose-regulated protein (GRP) and calpain siRNA or treating cells with ER stress chelators and caspase inhibitors. Interestingly, animal experiments illustrated a reduction in the tumor volume following ACDB treatment. Together, these results suggest that ACDB may be a novel tumor suppressor of chondrosarcoma, and this study demonstrates that the novel antitumor agent, ACDB, induced apoptosis by mitochondrial dysfunction and ER stress in human chondrosarcoma cells in vitro and in vivo.

  20. 1-Benzyl-2-Phenylbenzimidazole (BPB, a Benzimidazole Derivative, Induces Cell Apoptosis in Human Chondrosarcoma through Intrinsic and Extrinsic Pathways

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    Ju-Fang Liu

    2012-12-01

    Full Text Available In this study, we investigated the anticancer effects of a new benzimidazole derivative, 1-benzyl-2-phenyl -benzimidazole (BPB, in human chondrosarcoma cells. BPB-mediated apoptosis was assessed by the MTT assay and flow cytometry analysis. The in vivo efficacy was examined in a JJ012 xenograft model. Here we found that BPB induced apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 but not in primary chondrocytes. BPB induced upregulation of Bax, Bad and Bak, downregulation of Bcl-2, Bid and Bcl-XL and dysfunction of mitochondria in chondrosarcoma. In addition, BPB also promoted cytosolic releases AIF and Endo G. Furthermore, it triggered extrinsic death receptor-dependent pathway, which was characterized by activating Fas, FADD and caspase-8. Most importantly, animal studies revealed a dramatic 40% reduction in tumor volume after 21 days of treatment. Thus, BPB may be a novel anticancer agent for the treatment of chondrosarcoma.

  1. Endothelin-1 promotes epithelial–mesenchymal transition in human chondrosarcoma cells by repressing miR-300

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    Wu, Min-Huan; Huang, Pei-Han; Hsieh, Mingli; Tsai, Chun-Hao; Chen, Hsien-Te; Tang, Chih-Hsin

    2016-01-01

    Chondrosarcoma is a malignant tumor of mesenchymal origin predominantly composed of cartilage-producing cells. This type of bone cancer is extremely resistant to radiotherapy and chemotherapy. Surgical resection is the primary treatment, but is often difficult and not always practical for metastatic disease, so more effective treatments are needed. In particular, it would be helpful to identify molecular markers as targets for therapeutic intervention. Endothelin-1 (ET-1), a potent vasoconstrictor, has been shown to enhance chondrosarcoma angiogenesis and metastasis. We report that ET-1 promotes epithelial–mesenchymal transition (EMT) in human chondrosarcoma cells. EMT is a key pathological event in cancer progression, during which epithelial cells lose their junctions and apical-basal polarity and adopt an invasive phenotype. Our study verifies that ET-1 induces the EMT phenotype in chondrosarcoma cells via the AMP-activated protein kinase (AMPK) pathway. In addition, we show that ET-1 increases EMT by repressing miR-300, which plays an important role in EMT-enhanced tumor metastasis. We also show that miR-300 directly targets Twist, which in turn results in a negative regulation of EMT. We found a highly positive correlation between ET-1 and Twist expression levels as well as tumor stage in chondrosarcoma patient specimens. Therefore, ET-1 may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis. PMID:27602960

  2. Endothelin-1 promotes epithelial-mesenchymal transition in human chondrosarcoma cells by repressing miR-300.

    Science.gov (United States)

    Wu, Min-Huan; Huang, Pei-Han; Hsieh, Mingli; Tsai, Chun-Hao; Chen, Hsien-Te; Tang, Chih-Hsin

    2016-10-25

    Chondrosarcoma is a malignant tumor of mesenchymal origin predominantly composed of cartilage-producing cells. This type of bone cancer is extremely resistant to radiotherapy and chemotherapy. Surgical resection is the primary treatment, but is often difficult and not always practical for metastatic disease, so more effective treatments are needed. In particular, it would be helpful to identify molecular markers as targets for therapeutic intervention. Endothelin-1 (ET-1), a potent vasoconstrictor, has been shown to enhance chondrosarcoma angiogenesis and metastasis. We report that ET-1 promotes epithelial-mesenchymal transition (EMT) in human chondrosarcoma cells. EMT is a key pathological event in cancer progression, during which epithelial cells lose their junctions and apical-basal polarity and adopt an invasive phenotype. Our study verifies that ET-1 induces the EMT phenotype in chondrosarcoma cells via the AMP-activated protein kinase (AMPK) pathway. In addition, we show that ET-1 increases EMT by repressing miR-300, which plays an important role in EMT-enhanced tumor metastasis. We also show that miR-300 directly targets Twist, which in turn results in a negative regulation of EMT. We found a highly positive correlation between ET-1 and Twist expression levels as well as tumor stage in chondrosarcoma patient specimens. Therefore, ET-1 may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis.

  3. Apoptosis Signal-Regulating Kinase 1 Is Involved in Brain-Derived Neurotrophic Factor (BDNF)-Enhanced Cell Motility and Matrix Metalloproteinase 1 Expression in Human Chondrosarcoma Cells

    Science.gov (United States)

    Lin, Chih-Yang; Chang, Sunny Li-Yun; Fong, Yi-Chin; Hsu, Chin-Jung; Tang, Chih-Hsin

    2013-01-01

    Chondrosarcoma is the primary malignancy of bone that is characterized by a potent capacity to invade locally and cause distant metastasis, and is therefore associated with poor prognoses. Chondrosarcoma further shows a predilection for metastasis to the lungs. The brain-derived neurotrophic factor (BDNF) is a small molecule in the neurotrophin family of growth factors that is associated with the disease status and outcome of cancers. However, the effect of BDNF on cell motility in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma cell lines had significantly higher cell motility and BDNF expression compared to normal chondrocytes. We also found that BDNF increased cell motility and expression of matrix metalloproteinase-1 (MMP-1) in human chondrosarcoma cells. BDNF-mediated cell motility and MMP-1 up-regulation were attenuated by Trk inhibitor (K252a), ASK1 inhibitor (thioredoxin), JNK inhibitor (SP600125), and p38 inhibitor (SB203580). Furthermore, BDNF also promoted Sp1 activation. Our results indicate that BDNF enhances the migration and invasion activity of chondrosarcoma cells by increasing MMP-1 expression through a signal transduction pathway that involves the TrkB receptor, ASK1, JNK/p38, and Sp1. BDNF thus represents a promising new target for treating chondrosarcoma metastasis. PMID:23892595

  4. BL-038, a Benzofuran Derivative, Induces Cell Apoptosis in Human Chondrosarcoma Cells through Reactive Oxygen Species/Mitochondrial Dysfunction and the Caspases Dependent Pathway.

    Science.gov (United States)

    Liu, Ju-Fang; Chen, Chien-Yu; Chen, Hsien-Te; Chang, Chih-Shiang; Tang, Chih-Hsin

    2016-09-07

    Chondrosarcoma is a highly malignant cartilage-forming bone tumor that has the capacity to invade locally and cause distant metastasis. Moreover, chondrosarcoma is intrinsically resistant to conventional chemotherapy or radiotherapy. The novel benzofuran derivative, BL-038 (2-amino-3-(2,6-dichlorophenyl)-6-(4-methoxyphenyl)benzofuran-4-yl acetate), has been evaluated for its anticancer effects in human chondrosarcoma cells. BL-038 caused cell apoptosis in two human chondrosarcoma cell lines, JJ012 and SW1353, but not in primary chondrocytes. Treatment of chondrosarcoma with BL-038 also induced reactive oxygen species (ROS) production. Furthermore, BL-038 decreased mitochondrial membrane potential (MMP) and changed mitochondrial-related apoptosis, by downregulating the anti-apoptotic activity members (Bcl-2, Bcl-xL) and upregulating pro-apoptotic members (Bax, Bak) of the B-cell lymphoma 2 (Bcl-2) family of proteins, key regulators of the apoptotic machinery in cells. These results demonstrate that in human chondrosarcoma cells, the apoptotic and cytotoxic effects of BL-038 are mediated by the intrinsic mitochondria-mediated apoptotic pathway, which in turn causes the release of cytochrome c, the activation of caspase-9 and caspase-3, and the cleavage of poly (ADP-ribose) polymerase (PARP), to elicit apoptosis response. Our results show that the benzofuran derivative BL-038 induces apoptosis in chondrosarcoma cells.

  5. AMP-activated protein kinase activation mediates CCL3-induced cell migration and matrix metalloproteinase-2 expression in human chondrosarcoma

    Science.gov (United States)

    2013-01-01

    Chemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein-1α, is a cytokine involved in inflammation and activation of polymorphonuclear leukocytes. CCL3 has been detected in infiltrating cells and tumor cells. Chondrosarcoma is a highly malignant tumor that causes distant metastasis. However, the effect of CCL3 on human chondrosarcoma metastasis is still unknown. Here, we found that CCL3 increased cellular migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. Pre-treatment of cells with the MMP-2 inhibitor or transfection with MMP-2 specific siRNA abolished CCL3-induced cell migration. CCL3 has been reported to exert its effects through activation of its specific receptor, CC chemokine receptor 5 (CCR5). The CCR5 and AMP-activated protein kinase (AMPK) inhibitor or siRNA also attenuated CCL3-upregulated cell motility and MMP-2 expression. CCL3-induced expression of MMP-2 and migration were also inhibited by specific inhibitors, and inactive mutants of AMPK, p38 mitogen activated protein kinase (p38 or p38-MAPK), and nuclear factor κB (NF-κB) cascades. On the other hand, CCL3 treatment demonstrably activated AMPK, p38, and NF-κB signaling pathways. Furthermore, the expression levels of CCL3, CCR5, and MMP-2 were correlated in human chondrosarcoma specimens. Taken together, our results indicate that CCL3 enhances the migratory ability of human chondrosarcoma cells by increasing MMP-2 expression via the CCR5, AMPK, p38, and NF-κB pathways. PMID:24047437

  6. Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells

    Science.gov (United States)

    Li, Luyuan; Paz, Ana C.; Wilky, Breelyn A.; Johnson, Britt; Galoian, Karina; Rosenberg, Andrew; Hu, Guozhi; Tinoco, Gabriel; Bodamer, Olaf; Trent, Jonathan C.

    2015-01-01

    Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG) in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR-based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH-mutant chondrosarcomas. PMID:26368816

  7. Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells.

    Directory of Open Access Journals (Sweden)

    Luyuan Li

    Full Text Available Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2 were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR-based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH-mutant chondrosarcomas.

  8. rAAV Vectors as Safe and Efficient Tools for the Stable Delivery of Genes to Primary Human Chondrosarcoma Cells In Vitro and In Situ

    Directory of Open Access Journals (Sweden)

    Henning Madry

    2012-01-01

    Full Text Available Treatment of chondrosarcoma remains a major challenge in orthopaedic oncology. Gene transfer strategies based on recombinant adenoassociated viral (rAAV vectors may provide powerful tools to develop new, efficient therapeutic options against these tumors. In the present study, we tested the hypothesis that rAAV is adapted for a stable and safe delivery of foreign sequences in human chondrosarcoma tissue by transducing primary human chondrosarcoma cells in vitro and in situ with different reporter genes (E. coli lacZ, firefly luc, Discosoma sp. RFP. The effects of rAAV administration upon cell survival and metabolic activities were also evaluated to monitor possibly detrimental effects of the gene transfer method. Remarkably, we provide evidence that efficient and prolonged expression of transgene sequences via rAAV can be safely achieved in all the systems investigated, demonstrating the potential of the approach of direct application of therapeutic gene vectors as a means to treat chondrosarcoma.

  9. Resistin promotes tumor metastasis by down-regulation of miR-519d through the AMPK/p38 signaling pathway in human chondrosarcoma cells

    Science.gov (United States)

    Huang, Ho-Ning; Hung, Chih-Hung; Hsu, Chin-Jung; Fong, Yi-Chin; Hsu, Horng-Chaung; Huang, Yuan-Li; Tang, Chih-Hsin

    2015-01-01

    Resistin is a recently discovered adipocyte-secreting adipokine, which may play a critical role in modulating cancer pathogenesis. Chondrosarcoma is a highly malignant tumor known to frequently metastasize; however, the role of resistin in the metastasis of human chondrosarcoma is largely unknown. Here, we found that the expression of resistin was higher in chondrosarcoma biopsy tissues than in normal cartilage. Moreover, treatment with resistin increased matrix metalloproteinase (MMP)-2 expression and promoted cell migration in human chondrosarcoma cells. Co-transfection with microRNA (miR)-519d mimic resulted in reversed resistin-mediated cell migration and MMP-2 expression. Additionally, AMP-activated protein kinase (AMPK) and p38 inhibitors or siRNAs reduced the resistin-increased cell migration and miR-519d suppression, and inhibition of resistin expression resulted in suppression of MMP-2 expression and lung metastasis in vivo. Taken together, our results indicate that resistin promotes chondrosarcoma metastasis and MMP-2 expression through activation of the AMPK/p38 signaling pathway and down-regulation of miR-519d expression. Therefore, resistin may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis. PMID:25404641

  10. CCL5 promotes vascular endothelial growth factor expression and induces angiogenesis by down-regulating miR-199a in human chondrosarcoma cells.

    Science.gov (United States)

    Liu, Guan-Ting; Huang, Yuan-Li; Tzeng, Huey-En; Tsai, Chun-Hao; Wang, Shih-Wei; Tang, Chih-Hsin

    2015-02-28

    Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis. Angiogenesis is a critical step in tumor growth and metastasis. Chemokine CCL5 (previously called RANTES) has been shown to facilitate tumor progression and metastasis. However, the relationship of CCL5 with vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma is mostly unknown. In this study, CCL5 increased VEGF expression and also promoted chondrosarcoma medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. MicroRNA analysis was performed in CCL5-treated chondrosarcoma cells versus control cells to investigate the mechanism of CCL5-mediated promotion of chondrosarcoma angiogenesis. Among the miRNAs regulated by CCL5, miR-199a was the most downregulated miRNA after CCL5 treatment. In addition, co-transfection with miR-199a mimic reversed the CCL5-mediated VEGF expression and angiogenesis in vitro and in vivo. Moreover, overexpression of CCL5 increased tumor-associated angiogenesis and tumor growth by downregulating miR-199a in the xenograft tumor angiogenesis model. Taken together, these results demonstrated that CCL5 promotes VEGF-dependent angiogenesis in human chondrosarcoma cells by downregulating miR-199a. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. CCL5 promotes VEGF-dependent angiogenesis by down-regulating miR-200b through PI3K/Akt signaling pathway in human chondrosarcoma cells

    Science.gov (United States)

    Liu, Guan-Ting; Chen, Hsien-Te; Tsou, Hsi-Kai; Tan, Tzu-Wei; Fong, Yi-Chin; Chen, Po-Chen; Yang, Wei-Hung; Wang, Shih-Wei; Chen, Jui-Chieh; Tang, Chih-Hsin

    2014-01-01

    Chondrosarcoma is the second most common primary malignant bone cancer, with potential for local invasion and distant metastasis. Chemokine CCL5 (formerly RANTES) of the CC-chemokine family plays a crucial role in metastasis. Angiogenesis is essential for the cancer metastasis. However, correlation of CCL5 with vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma is still unknown. CCL5-mediated VEGF expression was assessed by qPCR, ELISA, and Western blotting. CCL5-induced angiogenesis was examined by migration and tube formation in endothelial progenitor cells in vitro. CCL5 increased VEGF expression and also promoted chondrosarcoma conditional medium-mediated angiogenesis in vitro and in vivo. Stimulation of chondrosarcoma with CCL5 augmented PI3K and Akt phosphorylation, while PI3K and Akt inhibitor or siRNA abolished CCL5-induced VEGF expression and angiogenesis. We also demonstrated CCL5 inhibiting miR-200b expression and miR-200b mimic reversing the CCL5-enhanced VEGF expression and angiogenesis. Moreover, in chondrosarcoma patients showed the positive correlation between CCL5 and VEGF; negative correlation between CCL5 and miR-200b. Taken together, results demonstrate CCL5 promoting VEGF-dependent angiogenesis in human chondrosarcoma cells by down-regulating miR-200b through PI3K/Akt signaling pathway. PMID:25301739

  12. Glycosaminoglycan synthesis by human chondrosarcoma

    International Nuclear Information System (INIS)

    Thonar, E.J-M.A.; Lyons, G.; Sweet, M.B.; Immelman, A.R.

    1979-01-01

    Human chondrosarcoma of low-grade malignancy was cultured in the presence of 35 S-sulphate and 3 H-glucosamine. The glycosaminoglycans isolated were fractioned on Ecteola cellulose and electrophoresed on cellulose acetate membranes before and after treatment with chondroitinase AC or Streptomyces hyaluronidase. The results demonstrated the in vitro synthesis of hyaluronate, chondroitin sulphate and keratan sulphate. The presence of keratan sulphate of large average chain length (approximately equal to 15 monosaccharides) supports the contention that chain length of keratan sulphate is inversely proportional to the degree of malignancy

  13. Amphiregulin enhances VEGF-A production in human chondrosarcoma cells and promotes angiogenesis by inhibiting miR-206 via FAK/c-Src/PKCδ pathway.

    Science.gov (United States)

    Wang, Chao-Qun; Huang, Yu-Wen; Wang, Shih-Wei; Huang, Yuan-Li; Tsai, Chun-Hao; Zhao, Yong-Ming; Huang, Bi-Fei; Xu, Guo-Hong; Fong, Yi-Chin; Tang, Chih-Hsin

    2017-01-28

    Chondrosarcoma is the second most common primary malignancy of bone after myeloma and osteosarcoma. Chondrosarcoma development may be linked to angiogenesis, which is principally elicited by vascular endothelial growth factor-A (VEGF-A). The expression of VEGF-A has been recognized as a prognostic marker in angiogenesis. Amphiregulin (AR), an epidermal growth factor receptor ligand, promotes tumor proliferation, metastasis and angiogenesis. However, the role of AR in VEGF-A expression and angiogenesis in human chondrosarcoma remains largely unknown. This current study shows that AR promoted VEGF-A production and induced angiogenesis of human endothelial progenitor cells. Moreover, AR-enhanced VEGF-A expression and angiogenesis involved the FAK, c-Src and PKCδ signaling pathways, while miR-206 expression was negatively mediated by AR via the FAK, c-Src and PKCδ pathways. Our results illustrate the clinical significance between AR, VEGF-A and miR-206, as well as tumor stage, in human chondrosarcoma. AR may represent a novel therapeutic target in the metastasis and angiogenesis of chondrosarcoma. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells.

    Science.gov (United States)

    Huang, Chun-Yin; Chang, An-Chen; Chen, Hsien-Te; Wang, Shih-Wei; Lo, Yuan-Shun; Tang, Chih-Hsin

    2016-09-01

    Chondrosarcoma is the second most frequently occurring type of bone malignancy characterized by distant metastatic propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumour lymphangiogenesis and lymphatic metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. In recent years, adiponectin has also been indicated as facilitating tumorigenesis, angiogenesis and metastasis. However, the effect of adiponectin on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has remained largely a mystery. In the present study, we have shown a clinical correlation between adiponectin and VEGF-C, as well as tumour stage, in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knock down inhibited lymphangiogenesis in vitro and in vivo We also found that adiponectin-induced VEGF-C is mediated by the calmodulin-dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK) and p38 signaling pathway. Furthermore, the expression of miR-27b was negatively regulated by adiponectin via the CaMKII, AMPK and p38 cascade. The present study is the first to describe the mechanism of adiponectin-promoted lymphangiogenesis by up-regulating VEGF-C expression in chondrosarcomas. Thus, adiponectin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  15. Brain-derived neurotrophic factor promotes VEGF-C-dependent lymphangiogenesis by suppressing miR-624-3p in human chondrosarcoma cells.

    Science.gov (United States)

    Lin, Chih-Yang; Wang, Shih-Wei; Chen, Yen-Ling; Chou, Wen-Yi; Lin, Ting-Yi; Chen, Wei-Cheng; Yang, Chen-Yu; Liu, Shih-Chia; Hsieh, Chia-Chu; Fong, Yi-Chin; Wang, Po-Chuan; Tang, Chih-Hsin

    2017-08-03

    Chondrosarcoma is the second most common primary malignancy of bone, and one of the most difficult bone tumors to diagnose and treat. It is well known that increased levels of vascular endothelial growth factor-C (VEGF-C) promote active tumor lymphangiogenesis and lymphatic tumor spread to regional lymph nodes. Brain-derived neurotrophic factor (BDNF) is known to promote metastasis in human chondrosarcoma cells. Knowing more about the mechanism of BDNF in VEGF-C expression and lymphangiogenesis in human chondrosarcoma would improve our understanding as how to prevent chondrosarcoma angiogenesis and metastasis, which currently lacks effective adjuvant treatment. Here, we found that BDNF expression was at least 2.5-fold higher in the highly migratory JJ012(S10) cell line as compared with the primordial cell line (JJ012). In addition, VEGF-C expression and secretion was markedly increased in JJ012(S10) cells. Conditioned medium from JJ012(S10) cells significantly promoted migration and tube formation of human lymphatic endothelial cells (LECs), whereas knockdown of BDNF attenuated LEC migration and tube formation by suppressing VEGF-C production in JJ012(S10) cells. Mechanistic investigations indicated that BDNF facilitated VEGF-C-dependent lymphangiogenesis through the MEK/ERK/mTOR signaling pathway. We also showed that microRNA (miR)-624-3p expression was negatively regulated by BDNF via the MEK/ERK/mTOR cascade. Importantly, BDNF knockdown profoundly inhibited tumor-associated lymphangiogenesis in vivo. Further analyses identified that BDNF promoted tumor lymphangiogenesis by downregulating miR-624-3p in human chondrosarcoma tissues. In conclusion, this study is the first to reveal the mechanism underlying BDNF-induced lymphangiogenesis. We suggest that BDNF may serve as a promising therapeutic target for the restriction of VEGF-C-mediated tumor lymphangiogenesis and lymphatic metastasis.

  16. Vγ9Vδ2 T cells and zoledronate mediate antitumor activity in an orthotopic mouse model of human chondrosarcoma.

    Science.gov (United States)

    Sun, L; Li, Y; Jiang, Z; Zhang, J; Li, H; Li, B; Ye, Z

    2016-06-01

    Chondrosarcoma (CS) is a cartilaginous malignant neoplasm characterized by resistance to conventional adjuvant therapy. The prognosis of unresectable or metastatic CS is poor. Therefore, it is imperative to explore novel therapeutic approaches to improve the treatment efficacy for those CS patients. Emerging data has implicated the synergistic antitumor activity of zoledronate (ZOL) and Vγ9Vδ2 T cells. However, whether ZOL-stimulated Vγ9Vδ2 T cells could infiltrate bone sarcoma and inhibit tumor growth has not been thoroughly answered yet. In this study, Vγ9Vδ2 T cells from healthy donors and CS patients were expanded in the presence of ZOL (1 μM) and IL-2 (400 IU/ml). The antitumor activity of Vγ9Vδ2 T cells to ZOL-pretreated human CS was examined both in vitro and in vivo. ZOL pretreatment substantially enhanced the cytotoxicity of Vγ9Vδ2 T cells to SW1353 and primary CS cells. ZOL potentiated the migration and cytotoxicity of Vγ9Vδ2 T cells to SW1353 in dose- and time-dependent manner. Moreover, weekly intravenous ZOL followed by Vγ9Vδ2 T cells inhibited subcutaneous xenograft growth. Thus, Vγ9Vδ2 T cells were able to infiltrate bone tumor and significantly suppressed the development of orthotopic SW1353 xenografts. Altogether, the study raises the possibility of combining ZOL with Vγ9Vδ2 T cells for CS treatment.

  17. Three new chondrosarcoma cell lines: one grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone

    Science.gov (United States)

    2012-01-01

    Background Chondrosarcoma is the second most common primary sarcoma of bone. High-grade conventional chondrosarcoma and dedifferentiated chondrosarcoma have a poor outcome. In pre-clinical research aiming at the identification of novel treatment targets, the need for representative cell lines and model systems is high, but availability is scarce. Methods We developed and characterized three cell lines, derived from conventional grade III chondrosarcoma (L835), and dedifferentiated chondrosarcoma (L2975 and L3252) of bone. Proliferation and migration were studied and we used COBRA-FISH and array-CGH for karyotyping and genotyping. Immunohistochemistry for p16 and p53 was performed as well as TP53 and IDH mutation analysis. Cells were injected into nude mice to establish their tumorigenic potential. Results We show that the three cell lines have distinct migrative properties, L2975 had the highest migration rate and showed tumorigenic potential in mice. All cell lines showed chromosomal rearrangements with complex karyotypes and genotypic aberrations were conserved throughout late passaging of the cell lines. All cell lines showed loss of CDKN2A, while TP53 was wild type for exons 5–8. L835 has an IDH1 R132C mutation, L2975 an IDH2 R172W mutation and L3252 is IDH wild type. Conclusions Based on the stable culturing properties of these cell lines and their genotypic profile resembling the original tumors, these cell lines should provide useful functional models to further characterize chondrosarcoma and to evaluate new treatment strategies. PMID:22928481

  18. Three new chondrosarcoma cell lines: one grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone

    International Nuclear Information System (INIS)

    Oosterwijk, Jolieke G van; Bovée, Judith VMG; Jong, Danielle de; Ruler, Maayke AJH van; Hogendoorn, Pancras CW; Dijkstra, PD Sander; Rijswijk, Carla SP van; Machado, Isidro; Llombart-Bosch, Antonio; Szuhai, Karoly

    2012-01-01

    Chondrosarcoma is the second most common primary sarcoma of bone. High-grade conventional chondrosarcoma and dedifferentiated chondrosarcoma have a poor outcome. In pre-clinical research aiming at the identification of novel treatment targets, the need for representative cell lines and model systems is high, but availability is scarce. We developed and characterized three cell lines, derived from conventional grade III chondrosarcoma (L835), and dedifferentiated chondrosarcoma (L2975 and L3252) of bone. Proliferation and migration were studied and we used COBRA-FISH and array-CGH for karyotyping and genotyping. Immunohistochemistry for p16 and p53 was performed as well as TP53 and IDH mutation analysis. Cells were injected into nude mice to establish their tumorigenic potential. We show that the three cell lines have distinct migrative properties, L2975 had the highest migration rate and showed tumorigenic potential in mice. All cell lines showed chromosomal rearrangements with complex karyotypes and genotypic aberrations were conserved throughout late passaging of the cell lines. All cell lines showed loss of CDKN2A, while TP53 was wild type for exons 5–8. L835 has an IDH1 R132C mutation, L2975 an IDH2 R172W mutation and L3252 is IDH wild type. Based on the stable culturing properties of these cell lines and their genotypic profile resembling the original tumors, these cell lines should provide useful functional models to further characterize chondrosarcoma and to evaluate new treatment strategies

  19. The epigenetic regulation of SOX9 by miR-145 in human chondrosarcoma.

    Science.gov (United States)

    Mak, Isabella W Y; Singh, Shalini; Turcotte, Robert; Ghert, Michelle

    2015-01-01

    Chondrosarcoma is the most common primary bone malignancy in the adult population with a high rate of pulmonary metastasis. Chondrosarcoma is managed with surgical excision as the tumors do not respond well to conventional chemotherapy or radiation therapy. Thus, there exists a dire need to develop systemic treatment options to target chondrosarcoma cells for metastatic spread. We hypothesized that the expression of miR-145 is low in chondrosarcoma, leading to decreased transcriptional control of SOX9 (the master regulator of chondrogenesis), and downstream activation of the transcription factor ETV5. We have previously shown that ETV5 activates MMP-2 expression in chondrosarcoma, which in turn increases local bone matrix resorption. In this study, we confirm high expression of SOX9 in human chondrosarcoma using real-time PCR, Western blotting, and immunofluorescence. An ETV5 promoter-reporter plasmid was transfected into chondrosarcoma cells to determine if SOX9 directly regulates the expression of ETV5. Co-transfection of the ETV5 promoter-plasmid with SOX9 lentivirus significantly increased the luciferase activity derived from the ETV5 promoter, from which the regulatory relationship between SOX9 and ETV5 is established. MiR-145 was found to be down-regulated in chondrosarcoma cell lines, patient samples, and further confirmed with a public sarcoma database. After stable miR-145 lentiviral transfection, the subsequent mRNA expression levels of SOX9, ETV5, and MMP-2 were significantly decreased in chondrosarcoma cells. The results generated by this study may have important clinical significance in the treatment of patients with chondrosarcoma in that targeted miRNA may have the potential to downregulate the upstream activators of proteases such as MMP-2. © 2014 Wiley Periodicals, Inc.

  20. Inhibition of Src by microRNA-23b increases the cisplatin sensitivity of chondrosarcoma cells.

    Science.gov (United States)

    Huang, Kai; Chen, Jun; Yang, Mo-Song; Tang, Yu-Jun; Pan, Feng

    2017-01-01

    Chondrosarcomas are malignant cartilage-forming tumors from low-grade to high-grade aggressive tumors characterized by metastasis. Cisplatin is an effective DNA-damaging anti-tumor agent for the treatment against a wide variety of solid tumors. However, chondrosarcomas are notorious for their resistance to conventional chemo- and radio- therapies. In this study, we report miR-23b acts as a tumor suppressor in chondrosarcoma. The expressions of miR-23b are down-regulated in chondrosarcoma patient samples and cell lines compared with adjacent normal tissues and human primary chondrocytes. In addition, overexpression of miR-23b suppresses chondrosarcoma cell proliferation. By comparison of the cisplatin resistant chondrosarcoma cells and parental cells, we observed miR-23b was significantly down regulated in cisplatin resistant cells. Moreover, we demonstrate here Src kinase is a direct target of miR-23b in chondrosarcoma cells. Overexpression of miR-23b suppresses Src-Akt pathway, leading to the sensitization of cisplatin resistant chondrosarcoma cells to cisplatin. This chemo-sensitivity effect by the miR-23b-mediated inhibition of Src-Akt pathway is verified with the restoration of Src kinase in miR-23b-overespressing chondrosarcoma cells, resulting in the acquirement of resistance to cisplatin. In summary, our study reveals a novel role of miR-23b in cisplatin resistance in chondrosarcoma and will contribute to the development of the microRNA-targeted anti-cancer therapeutics.

  1. Genome-wide mRNA and miRNA expression data analysis to screen for markers involved in sarcomagenesis in human chondrosarcoma cell lines

    Directory of Open Access Journals (Sweden)

    Biju Issac

    2014-12-01

    Full Text Available Genes and miRNAs involved in sarcomagenesis related pathways are unknown and therefore signaling events leading to mesenchymal cell transformation to sarcoma are poorly elucidated. Exiqon and Illumina microarray study on human chondrosarcoma JJ012 and chondrocytes C28 cell lines to compare and analyze the differentially expressed miRNAs and their gene targets was recently published in the Journal Tumor Biology in 2014. Here we describe in details the contents and quality controls for the miRNA and gene expression data associated with the study that is relevant to this dataset.

  2. miRNA-497 Negatively Regulates the Growth and Motility of Chondrosarcoma Cells by Targeting Cdc25A.

    Science.gov (United States)

    Lu, Yandong; Li, Fangguo; Xu, Tao; Sun, Jie

    2016-01-01

    Chondrosarcoma (CHS) is the second most common malignant bone sarcoma with increased risk of invasion and metastasis. However, the regulatory mechanisms of CHS tumorigenesis remain unknown. Here we investigated the novel role of miR-497 in regulating chondrosarcoma cell growth and cell cycle arrest. RT-PCR analysis showed that the expression of miR-497 is aberrantly downregulated in human chondrosarcoma samples and cells. After transfection with miR-497 mimic or antagomir, the proliferation and apoptosis of JJ012 and OUMS-27 chondrosarcoma cells were determined by CCK-8 assay and flow cytometric analysis, respectively. Results showed that the proliferation capacity of JJ012 and OUMS-27 cells was significantly decreased by miR-497 overexpression but increased by miR-497 repression. Apoptosis in both cell types was remarkably enhanced by miR-497 mimic but inhibited by miR-497 antagomir. By bioinformatics and luciferase reporter analysis, Cdc25A was proven to be a direct target of miR-497 in chondrosarcoma cells. Further studies indicated that miR-497 modulates the growth of chondrosarcoma cells by targeting Cdc25A, in which the cell cycle inhibitor p21 is involved through a p53-independent pathway. In conclusion, we demonstrated that miR-497 represents a potential tumor suppressor in human chondrosarcoma that regulates the growth of chondrosarcoma cells by targeting Cdc25A. This may provide a novel therapeutic target for chondrosarcoma.

  3. By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization.

    Science.gov (United States)

    Guan, Pei-Pei; Yu, Xin; Guo, Jian-Jun; Wang, Yue; Wang, Tao; Li, Jia-Yi; Konstantopoulos, Konstantinos; Wang, Zhan-You; Wang, Pu

    2015-04-20

    Interstitial fluid flow and associated shear stress are relevant mechanical signals in cartilage and bone (patho)physiology. However, their effects on chondrosarcoma cell motility, invasion and metastasis have yet to be delineated. Using human SW1353, HS.819.T and CH2879 chondrosarcoma cell lines as model systems, we found that fluid shear stress induces the accumulation of cyclic AMP (cAMP) and interleukin-1β (IL-1β), which in turn markedly enhance chondrosarcoma cell motility and invasion via the induction of matrix metalloproteinase-7 (MMP-7). Specifically, shear-induced cAMP and IL-1β activate PI3-K, ERK1/2 and p38 signaling pathways, which lead to the synthesis of MMP-7 via transactivating NF-κB and c-Jun in human chondrosarcoma cells. Importantly, MMP-7 upregulation in response to shear stress exposure has the ability to promote lung colonization of chondrosarcomas in vivo. These findings offer a better understanding of the mechanisms underlying MMP-7 activation in shear-stimulated chondrosarcoma cells, and provide insights on designing new therapeutic strategies to interfere with chondrosarcoma invasion and metastasis.

  4. Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic Resistance

    Science.gov (United States)

    Boehme, Karen A.; Schleicher, Sabine B.; Rolauffs, Bernd

    2018-01-01

    Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas with a peak incidence in adolescents and young adults, conventional and dedifferentiated chondrosarcomas mainly affect people in the 4th to 7th decade of life. To date, the cell type of chondrosarcoma origin is not clearly defined. However, it seems that mesenchymal stem and progenitor cells (MSPC) in the bone marrow facing a pro-proliferative as well as predominantly chondrogenic differentiation milieu, as is implicated in early stage osteoarthritis (OA) at that age, are the source of chondrosarcoma genesis. But how can MSPC become malignant? Indeed, only one person in 1,000,000 will develop a chondrosarcoma, whereas the incidence of OA is a thousandfold higher. This means a rare coincidence of factors allowing escape from senescence and apoptosis together with induction of angiogenesis and migration is needed to generate a chondrosarcoma. At early stages, chondrosarcomas are still assumed to be an intermediate type of tumor which rarely metastasizes. Unfortunately, advanced stages show a pronounced resistance both against chemo- and radiation-therapy and frequently metastasize. In this review, we elucidate signaling pathways involved in the genesis and therapeutic resistance of chondrosarcomas with a focus on MSPC compared to signaling in articular cartilage (AC). PMID:29361725

  5. Involvement of the Soluble Urokinase Receptor in Chondrosarcoma Cell Mobilization

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    Katia Bifulco

    2011-01-01

    Full Text Available High levels of urokinase receptor (uPAR in tissue and serum of patients with chondrosarcoma correlate with poor prognosis. First, we analyzed the uPAR levels in tissues and plasma of five patients affected by chondrosarcoma. Interestingly, very high levels of uPAR and its soluble forms (SuPAR were found on tumor cell surfaces and plasma, respectively, of two patients with lung metastases. Therefore, to investigate the role of SuPAR in chondrosaromas, we generated a primary cell culture from a chondrosarcoma tissue overexpressing uPAR on cell surfaces. We found that chondrosarcoma-like primary culture cells release a large amount of SuPAR in the medium. In vitro, SuPAR elicits chondrosarcoma cell migration likely through its uPAR88-92 sequence, since the DII88-183 or DIIDIIR88-284 uPAR domains retain motogen effect whereas DI1-87 or DIII184-284 domains, both lacking the uPAR88-92 sequence, are ineffective. Chondrosarcoma cells cross matrigel in response to SuPAR, and their invasion capability is abrogated by RERF peptide which inhibits uPAR88-92 signalling. These findings assign a role to uPAR in mobilizing chondrosarcoma cells and suggest that RERF peptide may be regarded as a prototype to generate new therapeutics for the chondrosarcoma treatment.

  6. New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance.

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    Monderer, David; Luseau, Alexandrine; Bellec, Amélie; David, Emmanuelle; Ponsolle, Stéphanie; Saiagh, Soraya; Bercegeay, Sylvain; Piloquet, Philippe; Denis, Marc G; Lodé, Laurence; Rédini, Françoise; Biger, Marine; Heymann, Dominique; Heymann, Marie-Françoise; Le Bot, Ronan; Gouin, François; Blanchard, Frédéric

    2013-10-01

    Chondrosarcomas are cartilage-forming, poorly vascularized tumors. They represent the second malignant primary bone tumor of adults after osteosarcoma, but in contrast to osteosarcoma they are resistant to chemotherapy and radiotherapy, surgical excision remaining the only therapeutic option. Few cell lines and animal models are available, and the mechanisms behind their chemoresistance remain largely unknown. Our goal was to establish new cell lines and animal cancer models from human chondrosarcoma biopsies to study their chemoresistance. Between 2007 and 2012, 10 chondrosarcoma biopsies were collected and used for cell culture and transplantation into nude mice. Only one transplanted biopsy and one injected cell line has engrafted successfully leading to conventional central high-grade chondrosarcoma similar to the original biopsies. In culture, two new stable cell lines were obtained, one from a dedifferentiated and one from a grade III conventional central chondrosarcoma biopsy. Their genetic characterization revealed triploid karyotypes, mutations in IDH1, IDH2, and TP53, deletion in CDKN2A and/or MDM2 amplification. These cell lines expressed mesenchymal membrane markers (CD44, 73, 90, 105) and were able to produce a hyaline cartilaginous matrix when cultured in chondrogenic three-dimensional (3D) pellets. Using a high-throughput quantitative RT-PCR approach, we observed that cell lines cultured in monolayer had lost expression of several genes implicated in cartilage development (COL2A1, COMP, ACAN) but restored their expression in 3D cultures. Chondrosarcoma cells in monolayer were sensitive to several conventional chemotherapeutic agents but became resistant to low doses of mafosfamide or doxorubicin when cultured in 3D pellets, in parallel with an altered nucleic accumulation of the drug. Our results indicate that the cartilaginous matrix produced by chondrosarcoma cells may impair diffusion of several drugs and thus contribute to chemoresistance

  7. Andrographolide Induces Cell Cycle Arrest and Apoptosis of Chondrosarcoma by Targeting TCF-1/SOX9 Axis.

    Science.gov (United States)

    Zhang, Huan-Tian; Yang, Jie; Liang, Gui-Hong; Gao, Xue-Juan; Sang, Yuan; Gui, Tao; Liang, Zu-Jian; Tam, Man-Seng; Zha, Zhen-Gang

    2017-12-01

    Chondrosarcoma is the second most malignant bone tumor with poor prognosis and limited treatment options. Thus, development of more effective treatments has become urgent. Recently, natural compounds derived from medicinal plants have emerged as promising therapeutic options via targeting multiple key cellular molecules. Andrographolide (Andro) is such a compound, which has previously been shown to induce cell cycle arrest and apoptosis in several human cancers. However, the molecular mechanism through which Andro exerts its anti-cancer effect on chondrosarcoma remains to be elucidated. In the present study, we showed that Andro-induced G2/M cell cycle arrest of chondrosarcoma by fine-tuning the expressions of several cell cycle regulators such as p21, p27, and Cyclins, and that prolonged treatment of cells with Andro caused pronounced cell apoptosis. Remarkably, we found that SOX9 was highly expressed in poor-differentiated chondrosarcoma, and that knockdown of SOX9 suppressed chondrosarcoma cell growth. Further, our results showed that Andro dose-dependently down-regulated SOX9 expression in chondrosarcoma cells. Concomitantly, an inhibition of T cell factor 1 (TCF-1) mRNA expression and an enhancement of TCF-1 protein degradation by Andro were observed. In contrast, the expression and subcellular localization of β-catenin were not altered upon the treatment of Andro, suggesting that β-catenin might not function as the primary target of Andro. Additionally, we provided evidence that there was a mutual regulation between TCF-1 and SOX9 in chondrosarcoma cells. In conclusion, these results highlight the potential therapeutic effects of Andro in treatment of chondrosarcoma via targeting the TCF-1/SOX9 axis. J. Cell. Biochem. 118: 4575-4586, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Differential Bystander Signaling Between Radioresistant Chondrosarcoma Cells and Fibroblasts After X-Ray, Proton, Iron Ion and Carbon Ion Exposures

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    Wakatsuki, Masaru, E-mail: wa@mbe.nifty.com [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts (United States); Magpayo, Nicole; Kawamura, Hidemasa; Held, Kathryn D. [Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts (United States)

    2012-09-01

    Purpose: Chondrosarcoma is well known as a radioresistant tumor, but the mechanisms underlying that resistance are still unclear. The bystander effect is well documented in the field of radiation biology. We investigated the bystander response induced by X-rays, protons, carbon ions, and iron ions in chondrosarcoma cells using a transwell insert co-culture system that precludes physical contact between targeted and bystander cells. Methods and Materials: Human chondrosarcoma cells were irradiated with 0.1-, 0.5-, 1-, and 2-Gy X-rays, protons, carbon ions or iron ions using a transwell insert co-culture system. Formation of micronuclei and p53 binding protein 1 staining in bystander and irradiated cells were analyzed and bystander signaling between mixed cultures of chondrosarcoma cells, and normal human skin fibroblasts was investigated. Results: In this study, we show that the fraction of cells with DNA damages in irradiated chondrosarcoma cells showed dose-dependent increases with all beams. However, the fraction of cells with DNA damages in all bystander chondrosarcoma cells did not show any change from the levels in control cells. In the bystander signaling between mixed cultures of chondrosarcoma cells and fibroblasts, the amount of micronucleus formation in all bystander chondrosarcoma cells co-cultured with irradiated fibroblasts were the same as the levels for control cells. However, all bystander fibroblasts co-cultured with irradiated chondrosarcoma cells showed significant increases in the fraction of micronucleated cells compared to the rate of control cells. Conclusions: We conclude that chondrosarcoma cells in the transwell insert co-culture system could release bystander stimulations but could not develop bystander responses.

  9. Differential Bystander Signaling Between Radioresistant Chondrosarcoma Cells and Fibroblasts After X-Ray, Proton, Iron Ion and Carbon Ion Exposures

    International Nuclear Information System (INIS)

    Wakatsuki, Masaru; Magpayo, Nicole; Kawamura, Hidemasa; Held, Kathryn D.

    2012-01-01

    Purpose: Chondrosarcoma is well known as a radioresistant tumor, but the mechanisms underlying that resistance are still unclear. The bystander effect is well documented in the field of radiation biology. We investigated the bystander response induced by X-rays, protons, carbon ions, and iron ions in chondrosarcoma cells using a transwell insert co-culture system that precludes physical contact between targeted and bystander cells. Methods and Materials: Human chondrosarcoma cells were irradiated with 0.1-, 0.5-, 1-, and 2-Gy X-rays, protons, carbon ions or iron ions using a transwell insert co-culture system. Formation of micronuclei and p53 binding protein 1 staining in bystander and irradiated cells were analyzed and bystander signaling between mixed cultures of chondrosarcoma cells, and normal human skin fibroblasts was investigated. Results: In this study, we show that the fraction of cells with DNA damages in irradiated chondrosarcoma cells showed dose-dependent increases with all beams. However, the fraction of cells with DNA damages in all bystander chondrosarcoma cells did not show any change from the levels in control cells. In the bystander signaling between mixed cultures of chondrosarcoma cells and fibroblasts, the amount of micronucleus formation in all bystander chondrosarcoma cells co-cultured with irradiated fibroblasts were the same as the levels for control cells. However, all bystander fibroblasts co-cultured with irradiated chondrosarcoma cells showed significant increases in the fraction of micronucleated cells compared to the rate of control cells. Conclusions: We conclude that chondrosarcoma cells in the transwell insert co-culture system could release bystander stimulations but could not develop bystander responses.

  10. BMP-7 enhances cell migration and αvβ3 integrin expression via a c-Src-dependent pathway in human chondrosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Jui-Chieh Chen

    Full Text Available Bone morphogenic protein (BMP-7 is a member of the transforming growth factor (TGF-beta superfamily, which is originally identified based on its ability to induce cartilage and bone formation. In recent years, BMP-7 is also defined as a potent promoter of cell motility, invasion, and metastasis. However, there is little knowledge of the role of BMP-7 and its cellular function in chondrosarcoma cells. In the present study, we investigated the biological impact of BMP-7 on cell motility using transwell assay. In addition, the intracellular signaling pathways were also investigated by pharmacological and genetic approaches. Our results demonstrated that treatment with exogenous BMP-7 markedly increased cell migration by activating c-Src/PI3K/Akt/IKK/NF-κB signaling pathway, resulting in the transactivation of αvβ3 integrin expression. Indeed, abrogation of signaling activation, by chemical inhibition or expression of a kinase dead form of the protein attenuated BMP-7-induced expression of integrin αvβ3 and cell migration. These findings may provide a useful tool for diagnostic/prognostic purposes and even therapeutically in late-stage chondrosarcoma as an anti-metastatic agent.

  11. Clear-cell chondrosarcoma of the maxilla Report of a case

    NARCIS (Netherlands)

    Slootweg, P.J.

    Clear-cell chondrosarcoma is a variant of chondrosarcoma which is characterized by a typical histomorphology and a very slow rate of growth. A case is presented in which the tumor was located in the maxilla.

  12. Development and characterization of a human three-dimensional chondrosarcoma culture for in vitro drug testing.

    Science.gov (United States)

    Voissiere, Aurélien; Jouberton, Elodie; Maubert, Elise; Degoul, Françoise; Peyrode, Caroline; Chezal, Jean-Michel; Miot-Noirault, Élisabeth

    2017-01-01

    It has been suggested that chemoresistance of chondrosarcoma (CHS), the cartilage tumor, is caused by the phenotypic microenvironmental features of the tumor tissue, mainly the chondrogenic extracellular matrix (ECM), and hypoxia. We developed and characterized a multicellular tumor spheroid (MCTS) of human chondrosarcoma HEMC-SS cells to gain insight into tumor cell biology and drug response. At Day 7, HEMC-SS spheroids exhibited a homogeneous distribution of proliferative Ki-67 positive cells, whereas in larger spheroids (Day 14 and Day 20), proliferation was mainly localized in the periphery. In the core of larger spheroids, apoptotic cells were evidenced by TUNEL assay, and hypoxia by pimonidazole staining. Interestingly, VEGF excretion, evidenced by ELISA on culture media, was detectable from Day 14 spheroids, and increased as the spheroids grew in size. HEMC-SS spheroids synthesized a chondrogenic extracellular matrix rich in glycosaminoglycans and type-2 collagen. Finally, we investigated the sensitivity of Day 7 and Day 14 chondrosarcoma MCTS to hypoxia-activated prodrug TH-302 and doxorubicin compared with their 2D counterparts. As expected, TH-302 exhibited higher cytotoxic activity on larger hypoxic spheroids (Day 14) than on non-hypoxic spheroids (Day 7), with multicellular resistance index (MCRI) values of 7.7 and 9.1 respectively. For doxorubicin, the larger-sized spheroids exhibited higher drug resistance (MCRI of 5.0 for Day 7 and 18.3 for Day 14 spheroids), possibly due to impeded drug penetration into the deep layer of spheroids, evidenced by its auto-fluorescence property. We have developed a model of human chondrosarcoma MCTS that combines an ECM rich in glycosaminoglycans with a high hypoxic core associated with VEGF excretion. This model could offer a more predictive in vitro chondrosarcoma system for screening drugs targeting tumor cells and their microenvironment.

  13. Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways

    Science.gov (United States)

    Wang, P; Chen, S-H; Hung, W-C; Paul, C; Zhu, F; Guan, P-P; Huso, DL; Kontrogianni-Konstantopoulos, A; Konstantopoulos, K

    2015-01-01

    Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm2) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified. PMID:25435370

  14. Curcumin blocks interleukin-1 signaling in chondrosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Thomas Kalinski

    Full Text Available Interleukin (IL-1 signaling plays an important role in inflammatory processes, but also in malignant processes. The essential downstream event in IL-1 signaling is the activation of nuclear factor (NF-κB, which leads to the expression of several genes that are involved in cell proliferation, invasion, angiogenesis and metastasis, among them VEGF-A. As microenvironment-derived IL-1β is required for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we investigated IL-1β-induced signal transduction and VEGF-A expression in C3842 and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis assays and NF-κB-related gene expression analyses. Curcumin is a substance which inhibits IL-1 signaling very early by preventing the recruitment of IL-1 receptor associated kinase (IRAK to the IL-1 receptor. We demonstrate that IL-1 signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells. We further show that Curcumin blocks IL-1β-induced angiogenesis and NF-κB-related gene expression. We suppose that IL-1 blockade is an additional treatment option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1 blocking agents.

  15. New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis

    Directory of Open Access Journals (Sweden)

    Dass Crispin R

    2010-06-01

    Full Text Available Abstract Background Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. Methods Two human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases. Results JJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5 resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. Conclusions The established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.

  16. The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells.

    Science.gov (United States)

    Ingangi, Vincenzo; Bifulco, Katia; Yousif, Ali Munaim; Ragone, Concetta; Motti, Maria Letizia; Rea, Domenica; Minopoli, Michele; Botti, Giovanni; Scognamiglio, Giuseppe; Fazioli, Flavio; Gallo, Michele; De Chiara, Annarosaria; Arra, Claudio; Grieco, Paolo; Carriero, Maria Vincenza

    2016-08-23

    The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration and uPAR88-92 is the minimal sequence required to induce cell motility and angiogenesis by interacting with the formyl peptide receptor type 1 (FPR1). In this study, we present evidence that the cyclization of the uPAR88-92 sequence generates a new potent inhibitor of migration, and extracellular matrix invasion of human osteosarcoma and chondrosarcoma cells expressing comparable levels of FPR1 on cell surface. In vitro, the cyclized peptide [SRSRY] prevents formation of capillary-like tubes by endothelial cells co-cultured with chondrosarcoma cells and trans-endothelial migration of osteosarcoma and chondrosarcoma cells. When chondrosarcoma cells were subcutaneously injected in nude mice, tumor size, intra-tumoral microvessel density and circulating tumor cells in blood samples collected before the sacrifice, were significantly reduced in animals treated daily with i.p-administration of 6 mg/Kg [SRSRY] as compared to animals treated with vehicle only. Our findings indicate that [SRSRY] prevents three key events occurring during the metastatic process of osteosarcoma and chondrosarcoma cells: the extracellular matrix invasion, the formation of a capillary network and the entry into bloodstream.

  17. Adiponectin promotes VEGF-A-dependent angiogenesis in human chondrosarcoma through PI3K, Akt, mTOR, and HIF-α pathway.

    Science.gov (United States)

    Lee, Hsiang-Ping; Lin, Chih-Yang; Shih, Jhao-Sheng; Fong, Yi-Chin; Wang, Shih-Wei; Li, Te-Mao; Tang, Chih-Hsin

    2015-11-03

    Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. On the other hand, angiogenesis is a critical step in tumor growth and metastasis. However, the relationship of adiponectin with vascular endothelial growth factor-A (VEGF-A) expression and angiogenesis in human chondrosarcoma is mostly unknown. In this study we first demonstrated that the expression of adiponectin was correlated with tumor stage of human chondrosarcoma tissues. In addition, we also found that adiponectin increased VEGF-A expression in human chondrosarcoma cells and subsequently induced migration and tube formation in human endothelial progenitor cells (EPCs). Adiponectin promoted VEGF-A expression through adiponectin receptor (AdipoR), phosphoinositide 3 kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF)-1α signaling cascades. Knockdown of adiponectin decreased VEGF-A expression and also abolished chondrosarcoma conditional medium-mediated tube formation in EPCs in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. Therefore, adiponectin is crucial for tumor angiogenesis and growth, which may represent a novel target for anti-angiogenic therapy in human chondrosarcoma.

  18. Global demethylation of rat chondrosarcoma cells after treatment with 5-aza-2'-deoxycytidine results in increased tumorigenicity.

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    Christopher A Hamm

    Full Text Available Abnormal patterns of DNA methylation are observed in several types of human cancer. While localized DNA methylation of CpG islands has been associated with gene silencing, the effect that genome-wide loss of methylation has on tumorigenesis is not completely known. To examine its effect on tumorigenesis, we induced DNA demethylation in a rat model of human chondrosarcoma using 5-aza-2-deoxycytidine. Rat specific pyrosequencing assays were utilized to assess the methylation levels in both LINEs and satellite DNA sequences following 5-aza-2-deoxycytidine treatment. Loss of DNA methylation was accompanied by an increase in invasiveness of the rat chondrosarcoma cells, in vitro, as well as by an increase in tumor growth in vivo. Subsequent microarray analysis provided insight into the gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation. In particular, two genes that may function in tumorigenesis, sox-2 and midkine, were expressed at low levels in control cells but upon 5-aza-2-deoxycytidine treatment these genes became overexpressed. Promoter region DNA analysis revealed that these genes were methylated in control cells but became demethylated following 5-aza-2-deoxycytidine treatment. Following withdrawal of 5-aza-2-deoxycytidine, the rat chondrosarcoma cells reestablished global DNA methylation levels that were comparable to that of control cells. Concurrently, invasiveness of the rat chondrosarcoma cells, in vitro, decreased to a level indistinguishable to that of control cells. Taken together these experiments demonstrate that global DNA hypomethylation induced by 5-aza-2-deoxycytidine may promote specific aspects of tumorigenesis in rat chondrosarcoma cells.

  19. Induction of the mesenchymal to epithelial transition by demethylation-activated microRNA-125b is involved in the anti-migration/invasion effects of arsenic trioxide on human chondrosarcoma.

    Science.gov (United States)

    Bao, Xing; Ren, Tingting; Huang, Yi; Wang, Shidong; Zhang, Fan; Liu, Kuisheng; Zheng, Bingxin; Guo, Wei

    2016-08-30

    In addition to treating acute promyelocytic leukemia, arsenic trioxide (ATO) suppresses other solid tumors, including chondrosarcoma. However, the effects of ATO on metastasis in chondrosarcoma cells, and the underlying molecular mechanisms remain unclear. The effects of ATO on the migratory and invasive capacities of chondrosarcoma cells were investigated by Wound healing, Transwell and EMT assays. The expression of miR-125b in human chondrosarcoma tissues and cell lines was detected by real-time PCR analysis. Bisulfite sequencing analysis (BSP) was used to detect the effects of ATO on the expression of miR-125b. The gain-of-function and loss-of-function experiments were performed on chondrosarcoma cell lines to investigate the effects of miR-125b on chondrosarcoma invasion, and to determine whether signal transducer and activator of transcription 3(Stat3) mediates these effects. Dual-luciferase reporter assay was used to identify whether Stat3 is a direct target of miR-125b. MiR-125b was significantly downregulated in human metastatic chondrosarcoma tissues and cell lines but not in non-metastatic chondrosarcoma tissues. ATO up-regulates the expression of miR-125b by the demethylation of DNA. ATO induces MET and attenuates the invasive capacities of chondrosarcoma cells through miR-125b. Stat3 was verified as a direct target of miR-125b, which is involved in ATO regulating EMT-associated traits. These findings, for the first time, provides evidence that the miR-125b-mediated inhibition of Stat3 is involved in the ATO-induced attenuation of metastasis in chondrosarcoma cells.

  20. WISP-3 inhibition of miR-452 promotes VEGF-A expression in chondrosarcoma cells and induces endothelial progenitor cells angiogenesis.

    Science.gov (United States)

    Lin, Chih-Yang; Tzeng, Huey-En; Li, Te-Mao; Chen, Hsien-Te; Lee, Yi; Yang, Yi-Chen; Wang, Shih-Wei; Yang, Wei-Hung; Tang, Chih-Hsin

    2017-06-13

    Chondrosarcoma is the second most prevalent general primary tumor of bone following osteosarcoma. Chondrosarcoma development may be linked to angiogenesis, which is principally elicited by vascular endothelial growth factor-A (VEGF-A). VEGF-A level has been recognized as a prognostic marker in angiogenesis. WNT1-inducible signaling pathway protein-3 (WISP)-3/CCN6 belongs to the CCN family and is involved in regulating several cellular functions, including cell proliferation, differentiation, and migration. Nevertheless, the effect of WISP-3 on VEGF-A production and angiogenesis in human chondrosarcoma remains largely unknown. This current study shows that WISP-3 promoted VEGF-A production and induced angiogenesis of human endothelial progenitor cells. Moreover, WISP-3-enhanced VEGF-A expression and angiogenesis involved the c-Src and p38 signaling pathways, while miR-452 expression was negatively affected by WISP-3 via the c-Src and p38 pathways. Our results illustrate the clinical significance of WISP-3, VEGF-A and miR-452 in human chondrosarcoma patients. WISP-3 may illustrate a novel therapeutic target in the metastasis and angiogenesis of chondrosarcoma.

  1. 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

  2. Chondroblastoma and clear cell chondrosarcoma: radiological and MRI characteristics with histopathological correlation

    International Nuclear Information System (INIS)

    Kaim, Achim H.; Huegli, Rolf; Bonel, Harald M.; Jundt, Gernot

    2002-01-01

    Objective: To analyze and compare the radiological and magnetic resonance imaging (MRI) appearances of chondroblastoma and clear cell chondrosarcoma with histopathological correlation. Design and patients: Twelve patients with histologically proven chondroblastoma and of another four patients with clear cell chondrosarcoma were investigated by radiographs and MRI (T1-, T2-weighted sequences, intravenous gadolinium application). Additionally, the clinical and radiologic data of seven cases of clear cell chondrosarcoma without available MRI were considered. The localization, calcification of tumor matrix, periosteal reaction, cortical bone and patterns of bone destruction were analyzed according to the Lodwick radiological grading system (LRGS). The signal intensity on T1- and T2-weighted sequences, characteristics of contrast enhancement, associated bone marrow edema, soft tissue reaction and joint involvement were evaluated. Histopathological specimens were available in all cases. Results: The age of patients with chondroblastoma (range 15-59 years, mean 22.3 years) was lower than that of those with clear cell chondrosarcoma (range 19-61 years, mean 36.6 years), and the lesions were smaller in the chondroblastoma group (range 1-4 cm, mean 2.3 cm) than in patients with clear cell chondrosarcoma (range 3-7.5 cm, mean 5.2 cm). The chondroblastomas were more confined to the epiphysis (10/12) than the clear cell chondrosarcomas. All chondroblastomas and clear cell chondrosarcomas except one were classified as grade 1A or 1B according to the LRGS; one clear cell chondrosarcoma was judged as grade 2. Signal intensity of the tumors on MRI was very heterogeneous in both groups. High signal intensity on T2-weighted MR images in chondroblastoma mostly corresponded to areas with aneurysmal bone cyst components and in clear cell chondrosarcoma to islands of hyaline cartilage. Contrast enhancement occurred in all tumors and tended to be more intense with clear cell

  3. Chondroblastoma and clear cell chondrosarcoma: radiological and MRI characteristics with histopathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kaim, Achim H.; Huegli, Rolf [Institute of Diagnostic Radiology, University Hospital Basle (Switzerland); Bonel, Harald M. [Institute of Clinical Radiology, University Hospital, Munich-Grosshadern (Germany); Jundt, Gernot [Institute of Pathology, University Hospital Basle (Switzerland)

    2002-02-01

    Objective: To analyze and compare the radiological and magnetic resonance imaging (MRI) appearances of chondroblastoma and clear cell chondrosarcoma with histopathological correlation. Design and patients: Twelve patients with histologically proven chondroblastoma and of another four patients with clear cell chondrosarcoma were investigated by radiographs and MRI (T1-, T2-weighted sequences, intravenous gadolinium application). Additionally, the clinical and radiologic data of seven cases of clear cell chondrosarcoma without available MRI were considered. The localization, calcification of tumor matrix, periosteal reaction, cortical bone and patterns of bone destruction were analyzed according to the Lodwick radiological grading system (LRGS). The signal intensity on T1- and T2-weighted sequences, characteristics of contrast enhancement, associated bone marrow edema, soft tissue reaction and joint involvement were evaluated. Histopathological specimens were available in all cases. Results: The age of patients with chondroblastoma (range 15-59 years, mean 22.3 years) was lower than that of those with clear cell chondrosarcoma (range 19-61 years, mean 36.6 years), and the lesions were smaller in the chondroblastoma group (range 1-4 cm, mean 2.3 cm) than in patients with clear cell chondrosarcoma (range 3-7.5 cm, mean 5.2 cm). The chondroblastomas were more confined to the epiphysis (10/12) than the clear cell chondrosarcomas. All chondroblastomas and clear cell chondrosarcomas except one were classified as grade 1A or 1B according to the LRGS; one clear cell chondrosarcoma was judged as grade 2. Signal intensity of the tumors on MRI was very heterogeneous in both groups. High signal intensity on T2-weighted MR images in chondroblastoma mostly corresponded to areas with aneurysmal bone cyst components and in clear cell chondrosarcoma to islands of hyaline cartilage. Contrast enhancement occurred in all tumors and tended to be more intense with clear cell

  4. In vitro evaluation of chondrosarcoma cells and canine chondrocytes on layer-by-layer (LbL) self-assembled multilayer nanofilms

    International Nuclear Information System (INIS)

    Shaik, J; Mohammed, J Shaikh; McShane, M J; Mills, D K

    2013-01-01

    Short-term cell–substrate interactions of two secondary chondrocyte cell lines (human chondrosarcoma cells, canine chondrocytes) with layer-by-layer self-assembled multilayer nanofilms were investigated for a better understanding of cellular-behaviour dependence on a number of nanofilm layers. Cell–substrate interactions were studied on polyelectrolyte multilayer nanofilms (PMNs) of eleven different biomaterials. Surface characterization of PMNs performed using AFM showed increasing surface roughness with increasing number of layers for most of the biomaterials. LDH-L and MTT assays were performed on chondrosarcoma cells and canine chondrocytes, respectively. A major observation was that 10-bilayer nanofilms exhibited lesser cytotoxicity towards human chondrosarcoma cells than their 5-bilayer counterparts. In the case of canine chondrocytes, BSA enhanced cell metabolic activity with increasing number of layers, underscoring the importance of the multilayer nanofilm architecture on cellular behaviour. (paper)

  5. Clear cell chondrosarcoma mimicking chondroblastoma in a skeletally immature patient

    International Nuclear Information System (INIS)

    Cannon, Christopher P.; Nelson, Scott D.; Seeger, Leanne L.; Eckardt, Jeffrey J.

    2002-01-01

    We report the case of a clear cell chondrosarcoma (CCCS) occurring in the femoral head of a 14-year-old skeletally immature boy. Radiographic examination revealed a well-defined, osteolytic lesion in the epiphysis of the femoral head. Given the patient's age and the radiographic appearance of the lesion, chondroblastoma was high on the differential diagnosis. A frozen section was performed at the time of open biopsy was felt to be consistent with either chondroblastoma or CCCS. CCCS in a skeletally immature patient was felt to be unlikely, so curettage and bone grafting was performed. Final pathology review, however, confirmed the diagnosis of CCCS. The patient was taken back to surgery 4 weeks later for a wide resection and hemiarthroplasty. (orig.)

  6. Clear cell chondrosarcoma mimicking chondroblastoma in a skeletally immature patient

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, Christopher P. [Department of Orthopaedic Surgery, Madigan Army Medical Center, Ft. Lewis, WA (United States); Nelson, Scott D. [Department of Pathology and Laboratory Medicine, University of California, Los Angeles School of Medicine, CA (United States); Seeger, Leanne L. [Department of Radiological Sciences, University of California, CA (United States); Eckardt, Jeffrey J. [Department of Orthopaedic Surgery, University of California, Los Angeles School of Medicine, CA (United States)

    2002-06-01

    We report the case of a clear cell chondrosarcoma (CCCS) occurring in the femoral head of a 14-year-old skeletally immature boy. Radiographic examination revealed a well-defined, osteolytic lesion in the epiphysis of the femoral head. Given the patient's age and the radiographic appearance of the lesion, chondroblastoma was high on the differential diagnosis. A frozen section was performed at the time of open biopsy was felt to be consistent with either chondroblastoma or CCCS. CCCS in a skeletally immature patient was felt to be unlikely, so curettage and bone grafting was performed. Final pathology review, however, confirmed the diagnosis of CCCS. The patient was taken back to surgery 4 weeks later for a wide resection and hemiarthroplasty. (orig.)

  7. Src kinases in chondrosarcoma chemoresistance and migration: dasatinib sensitises to doxorubicin in TP53 mutant cells

    Science.gov (United States)

    van Oosterwijk, J G; van Ruler, M A J H; Briaire-de Bruijn, I H; Herpers, B; Gelderblom, H; van de Water, B; Bovée, J V M G

    2013-01-01

    Background: Chondrosarcomas are malignant cartilage-forming tumours of bone. Because of their resistance to conventional chemotherapy and radiotherapy, currently no treatment strategies exist for unresectable and metastatic chondrosarcoma. Previously, PI3K/AKT/GSK3β and Src kinase pathways were shown to be activated in chondrosarcoma cell lines. Our aim was to investigate the role of these kinases in chemoresistance and migration in chondrosarcoma in relation to TP53 mutation status. Methods: We used five conventional and three dedifferentiated chondrosarcoma cell lines and investigated the effect of PI3K/AKT/GSK3β pathway inhibition (enzastaurin) and Src pathway inhibition (dasatinib) in chemoresistance using WST assay and live cell imaging with AnnexinV staining. Immunohistochemistry on tissue microarrays (TMAs) containing 157 cartilaginous tumours was performed for Src family members. Migration assays were performed with the RTCA xCelligence System. Results: Src inhibition was found to overcome chemoresistance, to induce apoptosis and to inhibit migration. Cell lines with TP53 mutations responded better to combination therapy than wild-type cell lines (P=0.002). Tissue microarray immunohistochemistry confirmed active Src (pSrc) signalling, with Fyn being most abundantly expressed (76.1%). Conclusion: These results strongly indicate Src family kinases, in particular Fyn, as a potential target for the treatment of inoperable and metastatic chondrosarcomas, and to sensitise for doxorubicin especially in the presence of TP53 mutations. PMID:23922104

  8. Fluoroquinolone's effect on growth of human chondrocytes and chondrosarcomas. In vitro and in vivo correlation

    DEFF Research Database (Denmark)

    Multhaupt, H A; Alvarez, J C; Rafferty, P A

    2001-01-01

    Clinical and in vitro studies have demonstrated that fluoroquinolones are toxic to chondrocytes; however, the exact mechanism of fluoroquinolone arthropathy is unknown. We investigated the toxicity of ciprofloxacin on normal cartilage and on cartilaginous tumors. Normal human cartilage, enchondroma...... with use of conventional light microscopy, electron microscopy, and immunohistochemistry to identify extracellular matrix, cell proliferation, and apoptosis. Cultures of normal chondrocytes expressed type-II collagen. Electron microscopy revealed a large amount of glycogen in the cells; the presence of fat...... of vimentin filaments. The treated chondrocytes showed a decrease in cell proliferation, but there was no induction of apoptosis or effect on the expression of extracellular matrix proteins. Ciprofloxacin-treated chondrosarcoma cultures and tissue samples showed changes in cartilage matrix composition...

  9. miR-125b acts as a tumor suppressor in chondrosarcoma cells by the sensitization to doxorubicin through direct targeting the ErbB2-regulated glucose metabolism.

    Science.gov (United States)

    Tang, Xian-ye; Zheng, Wei; Ding, Min; Guo, Kai-jin; Yuan, Feng; Feng, Hu; Deng, Bin; Sun, Wei; Hou, Yang; Gao, Lu

    2016-01-01

    Chondrosarcoma is the second most common type of primary bone malignancy in the United States after osteosarcoma. Surgical resections of these tumors are the only effective treatment to chondrosarcoma patients due to their resistance to conventional chemo- and radiotherapy. In this study, miR-125b was found to perform its tumor-suppressor function to inhibit glucose metabolism via the direct targeting of oncogene, ErbB2. We report miR-125b was downregulated in both chondrosarcoma patient samples and cell lines. The total 20 Asian chondrosarcoma patients showed significantly downregulated miR-125b expression compared with normal tissues. Meanwhile, miR-125 was downregulated in chondrosarcoma cells and doxorubicin resistant cells. Overexpression of miR-125 enhanced the sensitivity of both parental and doxorubicin resistant cells to doxorubicin through direct targeting on the ErbB2-mediated upregulation of glycolysis in chondrosarcoma cells. Moreover, restoration of the expression of ErbB2 and glucose metabolic enzymes in miR-125 pretransfected cells recovered the susceptibility to doxorubicin. Our study will provide a novel aspect on the overcoming chemoresistance in human chondrosarcoma cells and may help in the development of therapeutic strategies for the treatments of patients.

  10. Diacerein retards cell growth of chondrosarcoma cells at the G2/M cell cycle checkpoint via cyclin B1/CDK1 and CDK2 downregulation

    International Nuclear Information System (INIS)

    Lohberger, Birgit; Leithner, Andreas; Stuendl, Nicole; Kaltenegger, Heike; Kullich, Werner; Steinecker-Frohnwieser, Bibiane

    2015-01-01

    Chondrosarcoma is characterized for its lack of response to conventional cytotoxic chemotherapy, propensity for developing lung metastases, and low rates of survival. Research within the field of development and expansion of new treatment options for unresectable or metastatic diseases is of particular priority. Diacerein, a symptomatic slow acting drug in osteoarthritis (SYSADOA), implicates a therapeutic benefit for the treatment of chondrosarcoma by an antitumor activity. After treatment with diacerein the growth behaviour of the cells was analyzed with the xCELLigence system and MTS assay. Cell cycle was examined using flow cytometric analysis, RT-PCR, and western blot analysis of specific checkpoint regulators. The status for phosophorylation of mitogen-activated protein kinases (MAPKs) was analyzed with a proteome profiler assay. In addition, the possible impact of diacerein on apoptosis was investigated using cleaved caspase 3 and Annexin V/PI flow cytometric analysis. Diacerein decreased the cell viability and the cell proliferation in two different chondrosarcoma cell lines in a dose dependent manner. Flow cytometric analysis showed a classical G2/M arrest. mRNA and protein analysis revealed that diacerein induced a down-regulation of the cyclin B1-CDK1 complex and a reduction in CDK2 expression. Furthermore, diacerein treatment increased the phosphorylation of p38α and p38β MAPKs, and Akt1, Akt2, and Akt 3 in SW-1353, whereas in Cal-78 the opposite effect has been demonstrated. These observations accordingly to our cell cycle flow cytometric analysis and protein expression data may explain the G2/M phase arrest. In addition, no apoptotic induction after diacerein treatment, neither in the Cal-78 nor in the SW-1353 cell line was observed. Our results demonstrate for the first time that the SYSADOA diacerein decreased the viability of human chondrosarcoma cells and induces G2/M cell cycle arrest by CDK1/cyclin B1 down-regulation

  11. MicroRNA-494 inhibits cell proliferation and invasion of chondrosarcoma cells in vivo and in vitro by directly targeting SOX9.

    Science.gov (United States)

    Li, Jingyuan; Wang, Lijuan; Liu, Zongzhi; Zu, Chao; Xing, Fanfan; Yang, Pei; Yang, Yongkang; Dang, Xiaoqian; Wang, Kunzheng

    2015-09-22

    Accumulating evidence indicates that dysregulation of miRNAs could contribute to tumor growth and metastasis of chondrosarcoma by infuencing cell proliferation and invasion. In the current study, we are interested to examine the role of miRNAs in the carcinogenesis and progression of chondrosarcoma. Here, using comparative miRNA profiling of tissues and cells of chondrosarcoma and cartilage, we identified miR-494 as a commonly downregulated miRNA in the tissues of patients with chondrosarcoma and chondrosarcoma cancer cell line, and upregulation of miR-494 could inhibit proliferation and invasion of chondrosarcoma cancer cells in vivo and in vitro. Moreover, our data demonstrated that SOX9, the essential regulator of the process of cartilage differentiation, was the direct target and functional mediator of miR-494 in chondrosarcoma cells. And downregulation of SOX9 could also inhibit migration and invasion of chondrosarcoma cells. In the last, we identified low expression of miR-494 was significantly correlated with poor overall survival and prognosis of chondrosarcoma patients. Thus, miR-494 may be a new common therapeutic target and prognosis biomarker for chondrosarcoma.

  12. Toll like receptors TLR1/2, TLR6 and MUC5B as binding interaction partners with cytostatic proline rich polypeptide 1 in human chondrosarcoma.

    Science.gov (United States)

    Galoian, Karina; Abrahamyan, Silva; Chailyan, Gor; Qureshi, Amir; Patel, Parthik; Metser, Gil; Moran, Alexandra; Sahakyan, Inesa; Tumasyan, Narine; Lee, Albert; Davtyan, Tigran; Chailyan, Samvel; Galoyan, Armen

    2018-01-01

    Metastatic chondrosarcoma is a bone malignancy not responsive to conventional therapies; new approaches and therapies are urgently needed. We have previously reported that mTORC1 inhibitor, antitumorigenic cytostatic proline rich polypeptide 1 (PRP-1), galarmin caused a significant upregulation of tumor suppressors including TET1/2 and SOCS3 (known to be involved in inflammatory processes), downregulation of oncoproteins and embryonic stem cell marker miR-302C and its targets Nanog, c-Myc and Bmi-1 in human chondrosarcoma. To understand better the mechanism of PRP-1 action it was very important to identify the receptor it binds to. Nuclear pathway receptor and GPCR assays indicated that PRP-1 receptors are not G protein coupled, neither do they belong to family of nuclear or orphan receptors. In the present study, we have demonstrated that PRP-1 binding interacting partners belong to innate immunity pattern recognition toll like receptors TLR1/2 and TLR6 and gel forming secreted mucin MUC5B. MUC5B was identified as PRP-1 receptor in human chondrosarcoma JJ012 cell line using Ligand-receptor capture technology. Toll like receptors TLR1/2 and TLR6 were identified as binding interaction partners with PRP-1 by western blot analysis in human chondrosarcoma JJ012 cell line lysates. Immunocytochemistry experiments confirmed the finding and indicated the localization of PRP-1 receptors in the tumor nucleus predominantly. TLR1/2, TLR6 and MUC5B were downregulated in human chondrosarcoma and upregulated in dose-response manner upon PRP-1 treatment. Experimental data indicated that in this cellular context the mentioned receptors had tumor suppressive function.

  13. BMP and TGFbeta pathways in human central chondrosarcoma: enhanced endoglin and Smad 1 signaling in high grade tumors

    International Nuclear Information System (INIS)

    Boeuf, Stephane; Bovée, Judith VMG; Lehner, Burkhard; Akker, Brendy van den; Ruler, Maayke van; Cleton-Jansen, Anne-Marie; Richter, Wiltrud

    2012-01-01

    As major regulators of normal chondrogenesis, the bone morphogenic protein (BMP) and transforming growth factor β (TGFB) signaling pathways may be involved in the development and progression of central chondrosarcoma. In order to uncover their possible implication, the aim of this study was to perform a systematic quantitative study of the expression of BMPs, TGFBs and their receptors and to assess activity of the corresponding pathways in central chondrosarcoma. Gene expression analysis was performed by quantitative RT-PCR in 26 central chondrosarcoma and 6 healthy articular cartilage samples. Expression of endoglin and nuclear localization of phosphorylated Smad1/5/8 and Smad2 was assessed by immunohistochemical analysis. The expression of TGFB3 and of the activin receptor-like kinase ALK2 was found to be significantly higher in grade III compared to grade I chondrosarcoma. Nuclear phosphorylated Smad1/5/8 and Smad2 were found in all tumors analyzed and the activity of both signaling pathways was confirmed by functional reporter assays in 2 chondrosarcoma cell lines. Immunohistochemical analysis furthermore revealed that phosphorylated Smad1/5/8 and endoglin expression were significantly higher in high-grade compared to low-grade chondrosarcoma and correlated to each other. The BMP and TGFβ signaling pathways were found to be active in central chondrosarcoma cells. The correlation of Smad1/5/8 activity to endoglin expression suggests that, as described in other cell types, endoglin could enhance Smad1/5/8 signaling in high-grade chondrosarcoma cells. Endoglin expression coupled to Smad1/5/8 activation could thus represent a functionally important signaling axis for the progression of chondrosarcoma and a regulator of the undifferentiated phenotype of high-grade tumor cells

  14. BMP and TGFbeta pathways in human central chondrosarcoma: enhanced endoglin and Smad 1 signaling in high grade tumors

    Science.gov (United States)

    2012-01-01

    Background As major regulators of normal chondrogenesis, the bone morphogenic protein (BMP) and transforming growth factor β (TGFB) signaling pathways may be involved in the development and progression of central chondrosarcoma. In order to uncover their possible implication, the aim of this study was to perform a systematic quantitative study of the expression of BMPs, TGFBs and their receptors and to assess activity of the corresponding pathways in central chondrosarcoma. Methods Gene expression analysis was performed by quantitative RT-PCR in 26 central chondrosarcoma and 6 healthy articular cartilage samples. Expression of endoglin and nuclear localization of phosphorylated Smad1/5/8 and Smad2 was assessed by immunohistochemical analysis. Results The expression of TGFB3 and of the activin receptor-like kinase ALK2 was found to be significantly higher in grade III compared to grade I chondrosarcoma. Nuclear phosphorylated Smad1/5/8 and Smad2 were found in all tumors analyzed and the activity of both signaling pathways was confirmed by functional reporter assays in 2 chondrosarcoma cell lines. Immunohistochemical analysis furthermore revealed that phosphorylated Smad1/5/8 and endoglin expression were significantly higher in high-grade compared to low-grade chondrosarcoma and correlated to each other. Conclusions The BMP and TGFβ signaling pathways were found to be active in central chondrosarcoma cells. The correlation of Smad1/5/8 activity to endoglin expression suggests that, as described in other cell types, endoglin could enhance Smad1/5/8 signaling in high-grade chondrosarcoma cells. Endoglin expression coupled to Smad1/5/8 activation could thus represent a functionally important signaling axis for the progression of chondrosarcoma and a regulator of the undifferentiated phenotype of high-grade tumor cells. PMID:23088614

  15. Long non-coding RNA BCAR4 promotes chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway.

    Science.gov (United States)

    Shui, Xiaolong; Zhou, Chengwei; Lin, Wei; Yu, Yang; Feng, Yongzeng; Kong, Jianzhong

    2017-05-01

    Chondrosarcoma is one of the common malignant histologic tumors, very difficult to treat, but the concrete cause and mechanism have not yet been elucidated. The present study aimed to investigate the functional involvement of BCAR4 in chondrosarcoma and its potentially underlying mechanism. QRT-PCR and western blot were used to determine the expression of BCAR4 and mTOR signaling pathway proteins both in chondrosarcoma tissues and cells. Chondrosarcoma cell proliferation and migration were assessed by MTT assay and transwell migration assay, respectively. The expression vectors were constructed and used to modulate the expression of BCAR4 and mTOR. Chondrosarcoma xenograft mouse model was established by subcutaneous injection with chondrosarcoma cell lines. The tumor volume was monitored to evaluate the effect of BCAR4 on chondrosarcoma cell tumorigenicity. The expressions of BCAR4, p-mTOR and p-P70S6K were up-regulated in chondrosarcoma tissues and cell lines. Moreover, BCAR4 overexpression had significant promoting effect on cell proliferation and migration in chondrosarcoma cells. Furthermore, mTOR signaling pathway was epigenetically activated by BCAR4-induced hyperacetylation of histone H3. We also found that mTOR overexpression abolished the decrease of chondrosarcoma cell proliferation and migration induced by BCAR4 knockdown. In vivo experiments confirmed that BCAR4 overexpression significantly accelerated tumor growth, while the knockdown of BCAR4 significantly inhibited tumor growth. BCAR4 promoted chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway, and thus contributed to chondrosarcoma progression. Impact statement LncRNA BCAR4 promoted chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway, and thus contributed to chondrosarcoma progression.

  16. 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.)

  17. Towards new therapeutic strategies in chondrosarcoma

    NARCIS (Netherlands)

    Schrage, Yvonne Maria

    2009-01-01

    This thesis presents the identification of new targets for therapeutic treatment of chondrosarcoma, tumours that are highly insensitive to conventional chemo- and radiation thearapy. A relatively new array technique to identify active kinases in chondrosarcoma cell cultures was used, which

  18. Inhibition of mutant IDH1 decreases D-2-HG levels without affecting tumorigenic properties of chondrosarcoma cell lines.

    Science.gov (United States)

    Suijker, Johnny; Oosting, Jan; Koornneef, Annemarie; Struys, Eduard A; Salomons, Gajja S; Schaap, Frank G; Waaijer, Cathelijn J F; Wijers-Koster, Pauline M; Briaire-de Bruijn, Inge H; Haazen, Lizette; Riester, Scott M; Dudakovic, Amel; Danen, Erik; Cleton-Jansen, Anne-Marie; van Wijnen, Andre J; Bovée, Judith V M G

    2015-05-20

    Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found in a subset of benign and malignant cartilage tumors, gliomas and leukaemias. The mutant enzyme causes the production of D-2-hydroxyglutarate (D-2-HG), affecting CpG island and histone methylation. While mutations in IDH1/2 are early events in benign cartilage tumors, we evaluated whether these mutations play a role in malignant chondrosarcomas. Compared to IDH1/2 wildtype cell lines, chondrosarcoma cell lines harboring an endogenous IDH1 (n=3) or IDH2 mutation (n=2) showed up to a 100-fold increase in intracellular and extracellular D-2-HG levels. Specific inhibition of mutant IDH1 using AGI-5198 decreased levels of D-2-HG in a dose dependent manner. After 72 hours of treatment one out of three mutant IDH1 cell lines showed a moderate decrease in viability , while D-2-HG levels decreased >90%. Likewise, prolonged treatment (up to 20 passages) did not affect proliferation and migration. Furthermore, global gene expression, CpG island methylation as well as histone H3K4, -9, and -27 trimethylation levels remained unchanged. Thus, while IDH1/2 mutations cause enchondroma, malignant progression towards central chondrosarcoma renders chondrosarcoma growth independent of these mutations. Thus, monotherapy based on inhibition of mutant IDH1 appears insufficient for treatment of inoperable or metastasized chondrosarcoma patients.

  19. Bortezomib induces apoptosis and suppresses cell growth and metastasis by inactivation of Stat3 signaling in chondrosarcoma.

    Science.gov (United States)

    Bao, Xing; Ren, Tingting; Huang, Yi; Ren, Chongmin; Yang, Kang; Zhang, Hongliang; Guo, Wei

    2017-02-01

    Bortezomib, formerly known as PS341, is a novel proteasome inhibitor with in vitro and in vivo antineoplastic effects in many malignancies. However, diverse antitumor mechanisms of bortezomib have been identified in many investigations and preclinical studies. Understanding the molecular and cellular mechanisms through which bortezomib acts will improve the therapeutic utility of this drug in different cancer types. In the present study, we investigated the in vitro and in vivo effects of bortezomib on chondrosarcoma. Bortezomib selectively inhibited cell growth in chondrosarcoma cells but not in normal articular cartilage cells. In addition to growth inhibition, apoptosis and cell cycle arrest, bortezomib triggered alleviation of migratory and invasive properties of chondrosarcoma cells. Mechanistically, signal transducer and activator of transcription 3 (Stat3) and its downstream targets Bcl-2, cyclin D1 and c-Myc was inactivated by bortezomib treatment. Accordingly, small interfering RNA (siRNA)-mediated Stat3 knockdown enhanced bortezomib-induced apoptosis, and concomitantly enhanced the inhibitory effect of bortezomib on cell viability, migration and invasion. Moreover, while Slug, MMP9, MMP2, CD44, N-cadherin and vimentin, the mesenchymal cell markers, were repressed by bortezomib concomitant increased expression of E-cadherin was observed. In vivo, bortezomib downregulated Stat3 activity and mesenchymal cell marker expression, induced apoptosis and inhibition of metastasis and tumor growth. Together, inactivation of Stat3 signaling contributes to bortezomib-induced inhibition of tumor growth, migration and invation on chondrosarcoma. Bortezomib demonstrates an antineoplastic role on chondrosarcoma both in vitro and in vivo. These beneficial effects can be explained by bortezomib-mediated Stat3 supression. The present study suggests a promising therapeutics target in chondrosarcoma and probably in other kinds of metastatic malignant tumors.

  20. BAG3 promotes chondrosarcoma progression by upregulating the expression of β-catenin

    Science.gov (United States)

    Shi, Huijuan; Chen, Wenfang; Dong, Yu; Lu, Xiaofang; Zhang, Wenhui; Wang, Liantang

    2018-01-01

    To investigate the roles of B-cell lymphoma-2 associated athanogene 3 (BAG3) in human chondrosarcoma and the potential mechanisms, the expression levels of BAG3 were detected in the present study, and the associations between BAG3 and clinical pathological parameters, clinical stage as well as the survival of patients were analyzed. The present study detected BAG3 mRNA and protein expression in the normal cartilage cell line HC-a and in SW1353 chondrosarcoma cells by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The BAG3 protein expression in 59 cases of chondrosarcoma, 30 patients with endogenous chondroma and 8 cases of normal cartilage was semi-quantitatively analyzed using the immunohistochemical method. In addition, the BAG3 protein expression level, the clinical pathological parameters, clinical stage and the survival time of patients with chondrosarcoma were analyzed. The plasmid transfection method was employed to upregulate the expression BAG3 and small RNA interference to downregulate the expression of BAG3 in SW1353 cells. The expression levels of BAG3 protein and mRNA were significantly increased in the chondrosarcoma cell line when compared with the normal cartilage cell line. The immunohistochemistry results indicated that BAG3 protein was overexpressed in the tissue of human chondrosarcoma. Statistical analysis showed that the expression level of BAG3 was significantly increased in the different Enneking staging of patients with chondrosarcoma and Tumor staging, and there were no statistical differences in age, gender, histological classification and tumor size. In the in vitro experiments, the data revealed that BAG3 significantly promoted chondrosarcoma cell proliferation, colony-formation, migration and invasion; however, it inhibited chondrosarcoma cell apoptosis. It was observed that BAG3 upregulated β-catenin expression at the mRNA and protein levels. In addition, BAG3 induced the expression of runt

  1. BAG3 promotes chondrosarcoma progression by upregulating the expression of β-catenin.

    Science.gov (United States)

    Shi, Huijuan; Chen, Wenfang; Dong, Yu; Lu, Xiaofang; Zhang, Wenhui; Wang, Liantang

    2018-04-01

    To investigate the roles of B‑cell lymphoma‑2 associated athanogene 3 (BAG3) in human chondrosarcoma and the potential mechanisms, the expression levels of BAG3 were detected in the present study, and the associations between BAG3 and clinical pathological parameters, clinical stage as well as the survival of patients were analyzed. The present study detected BAG3 mRNA and protein expression in the normal cartilage cell line HC‑a and in SW1353 chondrosarcoma cells by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The BAG3 protein expression in 59 cases of chondrosarcoma, 30 patients with endogenous chondroma and 8 cases of normal cartilage was semi-quantitatively analyzed using the immunohistochemical method. In addition, the BAG3 protein expression level, the clinical pathological parameters, clinical stage and the survival time of patients with chondrosarcoma were analyzed. The plasmid transfection method was employed to upregulate the expression BAG3 and small RNA interference to downregulate the expression of BAG3 in SW1353 cells. The expression levels of BAG3 protein and mRNA were significantly increased in the chondrosarcoma cell line when compared with the normal cartilage cell line. The immunohistochemistry results indicated that BAG3 protein was overexpressed in the tissue of human chondrosarcoma. Statistical analysis showed that the expression level of BAG3 was significantly increased in the different Enneking staging of patients with chondrosarcoma and Tumor staging, and there were no statistical differences in age, gender, histological classification and tumor size. In the in vitro experiments, the data revealed that BAG3 significantly promoted chondrosarcoma cell proliferation, colony‑formation, migration and invasion; however, it inhibited chondrosarcoma cell apoptosis. It was observed that BAG3 upregulated β‑catenin expression at the mRNA and protein levels. In addition, BAG3 induced the

  2. MicroRNA‑10b suppresses the migration and invasion of chondrosarcoma cells by targeting brain‑derived neurotrophic factor.

    Science.gov (United States)

    Aili, Abudunaibi; Chen, Yong; Zhang, Hongqi

    2016-01-01

    MicroRNAs (miRs) can lead to mRNA degradation or inhibit protein translation through directly binding to the 3'‑untranslational region (UTR) of their target mRNAs. Deregulation of miR‑10b has been reported to be associated with chondrosarcoma. However, the role of miR‑10b in chondrosarcoma cell migration and invasion, as well as the underlying mechanisms, has not been investigated. In the present study, it was demonstrated that miR‑10b was notably downregulated in the JJ012 and SW1353 chondrosarcoma cell lines compared with the TC28a2 normal chondrocyte line. Treatment with DNA demethylating agent 5‑aza‑2'‑deoxycytidine and histone deacetylase inhibitor 4‑phenylbutyric acid, or transfection with miR‑10b mimics promoted the expression of miR‑10b, which further suppressed the migratory and invasive capacities of JJ012 chondrosarcoma cells. Moreover, brain‑derived neurotrophic factor (BDNF) was identified as a novel target of miR‑10b, and its protein expression level was negatively regulated by miR‑10b in JJ012 cells. Furthermore, overexpression of BDNF reversed the inhibitory effect of miR‑10b upregulation on the migration and invasion of JJ012 cells. In addition, the data suggest that matrix metalloproteinase 1 (MMP1) may be involved in the miR‑10b/BDNF‑mediated chondrosarcoma cell migration and invasion in JJ012 cells. In conclusion, these findings suggest that miR‑10b/BDNF may serve as a potential therapeutic target for chondrosarcoma.

  3. Screening for potential targets for therapy in mesenchymal, clear cell, and dedifferentiated chondrosarcoma reveals Bcl-2 family members and TGFβ as potential targets

    DEFF Research Database (Denmark)

    van Oosterwijk, Jolieke G; Meijer, Danielle; van Ruler, Maayke A J H

    2013-01-01

    . As in conventional chondrosarcoma, antiapoptotic proteins (Bcl-2, and/or Bcl-xl) were highly expressed in all subtypes. Inhibition with the BH-3 mimetic ABT-737 rendered dedifferentiated chondrosarcoma cell lines sensitive to doxorubicin or cisplatin. Our data indicate that antiapoptotic proteins may play...

  4. Testicular chondrosarcoma

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    Yalçinkaya Ulviye

    2003-01-01

    Full Text Available A case of primary chondrosarcoma of the testis is reported. A 40-year-old man presented a painless swelling of the right testis that he has been observing for 3 years. Gross examination of the resected specimen showed an encapsulated, gray to tan colored, roughly rounded tumor. Histologically, the tumor revealed a well-differentiated chondrosarcoma.

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

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    Mohammad Javad Kharazi Fard

    2012-02-01

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

  6. Diagnostic investigations of DKK-1 and PDCD5 expression levels as independent prognostic markers of human chondrosarcoma.

    Science.gov (United States)

    Zarea, Mojtaba; Mohammadian Bajgiran, Amirhossein; Sedaghati, Farnoush; Hatami, Negin; Taheriazam, Afshin; Yahaghi, Emad; Shakeri, Mohammadreza

    2016-07-01

    In this study, we investigated the expression levels of Dickkopf-1 (DKK-1) and programmed cell death 5 (PDCD5) by using quantitative real-time PCR and immunohistochemistry in patients with chondrosarcoma. The DKK-1 mRNA levels were significantly higher in chondrosarcoma when compared with the corresponding nontumor tissues (mean ± SD: 4.23 ± 1.54; 1.54 ± 0.87; P = 0.001). PDCD5 mRNA levels were remarkably deceased in tumor tissues when compared with corresponding nontumor tissues (mean ± SD: 1.94 ± 0.73; 5.42 ± 1.73; P = 0.001). The high and moderate DKK-1 expressions were observed for 60% of chondrosarcoma samples in comparison with 27.5% of corresponding nontumor tissues (P  =  0.001). Moreover, low expression of PDCD5 was found in 67.5% of the tumor tissues when compared with the nontumor tissues (32.5%; P = 0.002). The results of this study showed that high DKK-1 expression levels were strongly related to MSTS stage (P = 0.011) and the advancement of histological grade (P chondrosarcoma. © 2016 IUBMB Life, 68(7):597-601, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  7. Clear cell chondrosarcoma of the pelvis in a skeletally immature patient

    International Nuclear Information System (INIS)

    Ishida, Tsuyoshi; Yamamoto, Motoi; Machinami, Rikuo; Goto, Takahiro; Kawano, Hirotaka; Yamamoto, Aiichiro

    1999-01-01

    We report on a case of clear cell chondrosarcoma (CCCS) of the left iliac bone in a 12-year-old skeletally immature boy. Radiographic examination revealed an aggressive osteolytic lesion with areas of mineralization. Fluid-fluid levels were seen on T2-weighted MR images. Laboratory data showed slight elevation of serum alkaline phosphatase. The biopsy specimen showed histological features of CCCS with some resemblance to osteosarcoma, such as prominent irregular osteoid formation among clear tumor cells. Surgical treatment was accomplished without pre- or post-operative chemotherapy. Because of the patient's age, elevated serum alkaline phosphatase, and histopathology with prominent osteoid production, this case could be confused with osteosarcoma. Although CCCS is an extremely rare bone tumor in children, it is important to be aware that it may arise in a skeletally immature patient. CCCS, unlike osteosarcoma, is not treated with neo-adjuvant chemotherapy. (orig.)

  8. Dedifferentiated Chondrosarcoma of the Larynx.

    Science.gov (United States)

    Fidai, Shiraz S; Ginat, Daniel T; Langerman, Alexander J; Cipriani, Nicole A

    2016-09-01

    Primary dedifferentiated chondrosarcoma occurring in the larynx is a rare head and neck malignancy. The cases reported in the literature suggest male gender predilection and variable clinical outcomes ranging from disease-free survival to disease-related death. Although a calcified matrix is suggestive of chondrosarcoma, the dedifferentiated component is not readily appreciated on conventional imaging modalities and thorough tissue sampling is necessary for confirming the diagnosis. Histologically, there is an abrupt transition from a well-differentiated chondrosarcoma to a high-grade spindle cell component, which can show focal heterologous differentiation. These features are exemplified in this sine qua non radiology-pathology correlation article.

  9. Chondrosarcoma of the nasal septum.

    Science.gov (United States)

    Indudharan, R; Das, P K; Azman, A A; Suhaiza, S

    1998-08-01

    A case of chondrosarcoma of the nasal septum is presented with the result of treatment. The patient was admitted for a growth in the nose of four years' duration. Fine needle aspiration for cytological examination was suggestive of squamous cell carcinoma. She was treated with lateral rhinotomy and wide excision followed by septorhinoplasty. Histological examination showed that the lesion was chondrosarcoma. The patient remained free of disease 26 months after surgery.

  10. Dedifferentiated chondrosarcoma

    International Nuclear Information System (INIS)

    Mercuri, M.; Picci, P.; Campanacci, L.; Rulli, E.

    1995-01-01

    We reviewed 74 cases of dedifferentiated central and peripheral chondrosarcoma. The diagnosis is often suspected on the basis of the clinical course and careful evaluation of the radiographic characteristics. Central dedifferentiated chondrosarcoma can be classified radiographically into three types. In type 1 (36 cases in our review) the radiographic features are the same as those of a central chondrosarcoma, with the addition of a region with very aggressive radiographic features. Type 2 lesions (20 cases) resemble the underlying benign enchondroma but also have destructive changes and/or a large soft tissue mass. Type 3 lesions (8 cases) are not distinctive radiographically and present as a very high grade destructive lesion of bone. These cases are diagnosed following biopsy or tumour resection. The prognosis of these tumours is extremely poor, with 13% overall 5-year survival in this series. Improved survival was found in those cases where diagnosis was prompt and surgical treatment with a wide or radical margin was attained. No benefit was found from the use of adjuvant chemotherapy or radiotherapy. Thus, early recognition of the characteristic radiographic features, adequate histological sampling, and wide or radical surgical margins are necessary for satisfactory management of this highly malignant variant of chondrosarcoma. (orig.)

  11. Sternal chondrosarcoma

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    Nelson Perelman Rosenberg

    2003-01-01

    Full Text Available Sternal neoplasms are extremely rare. It is difficult to make prospective evaluations due to the lack of consistent reports in the literature. The authors report the case of a woman in her seventies, who presented a chondrosarcoma of the sternum, treated by them.

  12. Suppressed invasive and migratory behaviors of SW1353 chondrosarcoma cells through the regulation of Src, Rac1 GTPase, and MMP13.

    Science.gov (United States)

    Xu, Wenxiao; Wan, Qiaoqiao; Na, Sungsoo; Yokota, Hiroki; Yan, Jing-Long; Hamamura, Kazunori

    2015-12-01

    Chondrosarcoma is the second frequent type of primary bone cancer. In response to stress to the endoplasmic reticulum, activation of eIF2α-mediated signaling is reported to induce apoptosis. However, its effects on invasive and migratory behaviors of chondrosarcoma have not been understood. Focusing on potential roles of Src kinase, Rac1 GTPase, and MMP13, we investigated eIF2α-driven regulation of SW1353 chondrosarcoma cells. In particular, we employed two chemical agents (salubrinal, Sal; and guanabenz, Gu) that elevate the level of eIF2α phosphorylation. The result revealed that both Sal and Gu reduced invasion and motility of SW1353 chondrosarcoma cells in a dose dependent manner. Live imaging using a fluorescent resonance energy transfer (FRET) technique showed that Sal and Gu downregulated activities of Src kinase as well as Rac1 GTPase in an eIF2α dependent manner. RNA interference experiments supported an eIF2α-mediated regulatory network in the inhibitory role of Sal and Gu. Partial silencing of MMP13 also suppressed malignant phenotypes of SW1353 chondrosarcoma cells. However, MMP13 was not regulated via eIF2α since administration of Sal but not Gu reduced expression of MMP13. In summary, we demonstrate that eIF2α dependent and independent pathways regulate invasion and motility of SW1353 chondrosarcoma cells, and inactivation of Src, Rac1, and MMP13 by Sal could provide a potential adjuvant therapy for combating metastatic chondrosarcoma cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. NYESO-1/LAGE-1s and PRAME are targets for antigen specific T cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine.

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    Seth M Pollack

    Full Text Available Chondrosarcoma has no proven systemic option in the metastatic setting. The development of a non-cross-resistant strategy, such as cellular immunotherapy using antigen-specific T cells would be highly desirable. NY-ESO-1 and PRAME are members of the Cancer Testis Antigen (CTA family that have been identified as promising targets for T cell therapy. LAGE-1 is a cancer testis antigen 90% homologous to NY-ESO-1, sharing the 157-165 A*0201 NY-ESO-1 epitope with its transcript variant, LAGE-1s. A number of CTA's have been induced using 5-Aza-2-Deoxycitabine (5-Aza-dC in other cancers. We sought to evaluate the feasibility of targeting chondrosarcoma tumors using NY-ESO-1/LAGE-1s and PRAME specific T cells using 5-Aza-dC to induce antigen expression.We used 11 flash frozen tumors from the University of Washington tumor bank to test for the expression of NY-ESO-1, PRAME, LAGE-1s and LAGE-1L in chondrosarcoma tumors. Using four chondrosarcoma cell lines we tested the expression of these CTA's with and without 5-Aza-dC treatments. Finally, using NY-ESO-1/LAGE-1s and PRAME specific effectors that we generated from sarcoma patients, we evaluated the ability of these T cells to lyse A*0201 expressing chondrosarcoma cell lines in vitro both with and without 5-Aza-dC treatment.A minority (36% of chondrosarcoma tumors expressed either NY-ESO-1 or LAGE-1s at >10% of our reference value and none expressed PRAME at that level. However, in all four of the chondrosarcoma cell lines tested, NY-ESO-1 and PRAME expression could be induced following treatment with 5-Aza-dC including in cell lines where expression was absent or barely detectable. Furthermore, NY-ESO-1/LAGE-1s and PRAME specific CD8+ effector T cells were able to specifically recognize and lyse A*0201 expressing chondrosarcoma cell lines following 5-Aza-dC treatment.These data suggest that adoptive immunotherapy in combination with 5-Aza-dC may be a potential strategy to treat unresectable or metastatic

  14. HDAC6 inhibition suppresses chondrosarcoma by restoring the expression of primary cilia.

    Science.gov (United States)

    Xiang, Wei; Guo, Fengjing; Cheng, Weiting; Zhang, Jiaming; Huang, Junming; Wang, Rui; Ma, Zhongxi; Xu, Kai

    2017-07-01

    Chondrosarcoma is a bone tumor characterized by the secretion of a cartilage-like extracellular matrix. It has been proved to lack extracellular sensor primary cilia. This study aimed to illustrate a feasible therapeutic method for chondrosarcoma by regulating primary cilia assembly through inhibiting histone deacetylases 6 (HDAC6) activation. In order to detect the interaction between primary cilia and HDAC6 in human chondrosarcoma, Tubastatin A and small interfering RNA (siRNA) were used to inhibit the endogenous expression of HDAC6. Cell viability test and Transwell assay were applied to evaluate the effects of malignant biological properties. Primary cilia staining and related proteins were detected. The abnormal expression of HDAC6 and cilia intraflagellar transport protein 88 (IFT88) was found in chondrosarcoma tissues. The inhibition of HDAC6 could downregulate the proliferation of chondrosarcoma cells in a concentration- and time-dependent manner and suppress the invasion capacity of tumor cells. Besides, the downregulation of HDAC6 exhibited a negative effect on the proliferation of relevant proteins but a positive effect on the primary cilia-related expression of IFT88 and acetylated α-tubulin. Primary cilia restoration could be observed after HDAC6 siRNA transfection. The Aurora A-HDAC6 cascade was involved in regulating primary cilia resorption by affecting α-tubulin deacetylation and Tubastatin A could inhibit chondrosarcoma cell growth in vivo. These results indicate that restricting HDAC6 can restore primary cilia assembly accompanied with suppressed chondrosarcoma cell proliferation and invasion capacities. Thus, promoting primary cilia restoration by targeting HDAC6 may be a feasible potential therapeutic method for chondro-sarcoma treatment.

  15. Berberine Reduces the Metastasis of Chondrosarcoma by Modulating the αvβ3 Integrin and the PKCδ, c-Src, and AP-1 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Chi-Ming Wu

    2013-01-01

    Full Text Available Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis, especially to the lungs. Patients diagnosed with chondrosarcoma have poor prognosis. Berberine, an active component of the Ranunculaceae and Papaveraceae families of plant, has been proven to induce tumor apoptosis and to prevent the metastasis of cancer cells. However, the effects of berberine in human chondrosarcoma are largely unknown. In this study, we found that berberine did not induce cell apoptosis in human primary chondrocytes and chondrosarcoma cells. However, at noncytotoxic concentrations, berberine reduced the migration and invasion of chondrosarcoma cancer cells. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. We also found that incubation of chondrosarcoma cells with berberine reduced mRNA transcription for, and cell surface expression of, the αvβ3 integrin, with additional inhibitory effects on PKCδ, c-Src, and NF-κB activation. Thus, berberine may be a novel antimetastasis agent for the treatment of metastatic chondrosarcoma.

  16. Paeonol Suppresses Chondrosarcoma Metastasis through Up-Regulation of miR-141 by Modulating PKCδ and c-Src Signaling Pathway

    Science.gov (United States)

    Horng, Chi-Ting; Shieh, Po-Chuen; Tan, Tzu-Wei; Yang, Wei-Hung; Tang, Chih-Hsin

    2014-01-01

    Chondrosarcoma, a primary malignant bone cancer, has potential for local invasion and distant metastasis, especially to the lungs. Patients diagnosed with it show poor prognosis. Paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active compound of traditional Chinese remedy Paeonia lactiflora Pallas, exhibits anti-inflammatory and anti-tumor activity; whether paeonol regulates metastatic chondrosarcoma is largely unknown. Here, we find paeonol do not increase apoptosis. By contrast, at non-cytotoxic concentrations, paeonol suppresses migration and invasion of chondrosarcoma cells. We also demonstrate paeonol enhancing miR-141 expression and miR-141 inhibitor reversing paeonol-inhibited cell motility; paeonol also reduces protein kinase C (PKC)δ and c-Src kinase activity. Since paeonol inhibits migration and invasion of human chondrosarcoma via up-regulation of miR-141 via PKCδ and c-Src pathways, it thus might be a novel anti-metastasis agent for treatment of metastatic chondrosarcoma. PMID:24992595

  17. Dedifferentiated chondrosarcoma: an aggressive variant of chondrosarcoma.

    Science.gov (United States)

    Bharath, Gangadhara; Burrah, Rajaram; Shivakumar, Kuppuswamy; Manjunath, Suraj; Bhanumathi, Rao

    2015-02-01

    Dedifferentiated chondrosarcomas are a rare and aggressive subtype of chondrosarcoma with a bimorphic pattern on histopathology. Rib is a rare site of dedifferentiated chondrosarcoma. Diagnosis of this subtype preoperatively can be challenging. Treatment options for dedifferentiated chondrosarcoma are limited because they are chemoresistant, and therefore adequate surgery forms the main stay of treatment. We present our experience with a dedifferentiated chondrosarcoma of the rib, and discuss the management of this rare entity. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. MiR-129-5p Inhibits Proliferation and Invasion of Chondrosarcoma Cells by Regulating SOX4/Wnt/β-Catenin Signaling Pathway.

    Science.gov (United States)

    Zhang, Peng; Li, Jifeng; Song, Yuze; Wang, Xiao

    2017-01-01

    Recently, microRNAs (miRNA) have been identified as novel regulators in Chondrosarcoma (CHS). This study was aimed to identify the roles of miR-129-5p-5p in regulation of SOX4 and Wnt/β-catenin signaling pathway, as well as cell proliferation and apoptosis in chondrosarcomas. Tissue samples were obtained from chondrosarcoma patients. Immunohistochemistry, real-time quantitative RT-PCR (RT-qPCR) and western blot analysis were performed to detect the expressions of miR-129-5p and SOX4. Luciferase assay was conducted to confirm that miR-129-5p directly targeted SOX4 mRNA. Manipulations of miR-129-5p and SOX4 expression were achieved through cell transfection. Cell proliferation, migration and apoptosis were evaluated by CCK-8 assay, colony forming assay, wound healing assay and flow cytometry in vitro. For in vivo experiment, the tumor xenograft model was established to evaluate the effects of miR-129-5p and SOX4 on chondrosarcomas. The expression of miR-129-5p was significantly down-regulated in chondrosarcoma tissues as well as cells in comparison with normal ones, while SOX4 was over-activated. Further studies suggested that miR-129-5p suppressed cell proliferation, migration and promoted apoptosis by inhibiting SOX4 and Wnt/β-catenin pathway. MiR-129-5p inhibits the Wnt/β-catenin signaling pathway by targeting SOX4 and further suppresses cell proliferation, migration and promotes apoptosis in chondrosarcomas. © 2017 The Author(s). Published by S. Karger AG, Basel.

  19. 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

  20. Suppression of chondrosarcoma cells by 15-deoxy-Δ12,14-prostaglandin J2 is associated with altered expression of Bax/Bcl-xL and p21

    International Nuclear Information System (INIS)

    Shen, Zheng-Nan; Nishida, Keiichiro; Doi, Hideyuki; Oohashi, Toshitaka; Hirohata, Satoshi; Ozaki, Toshifumi; Yoshida, Aki; Ninomiya, Yoshifumi; Inoue, Hajime

    2005-01-01

    We previously reported that 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), the most potent agonist for peroxisome proliferator-activated receptor γ (PPARγ), induces apoptosis of human chondrosarcoma cell line OUMS-27. The current study aimed to explore the mechanism of 15d-PGJ 2 -induced apoptosis and inhibition of cell proliferation in OUMS-27 cells. The preliminary results of cDNA microarray analysis showed the down-regulation of anti-apoptotic Bcl-xL and up-regulation of pro-apoptotic Bax in the process of 15d-PGJ 2 -induced apoptosis. These changes were further confirmed at mRNA and protein levels by RT-PCR and Western blot analysis, respectively. Among cyclin-dependent kinase inhibitors, p21 was induced and up-regulated by 15d-PGJ 2 , but p16 and p27 were not changed, suggesting that the involvement of p21 in inhibition of cell proliferation. Activation of caspase-3 by 15d-PGJ 2 was partly, but not completely, blocked by PPARγ antagonist (GW9662) suggesting the 15d-PGJ 2 exerted its effect by PPARγ-dependent and -independent pathways. Interestingly, immunohistochemical study on human chondrosarcoma samples revealed that Bcl-xL is frequently expressed by tumor cells. The results of the current study suggest that the potential ability of 15d-PGJ 2 in regulation of cell cycle and inhibition of Bcl-xL expression might be beneficial in the development of novel pharmacological agents for chondrosarcoma

  1. Clear cell chondrosarcoma: radiographic, computed tomographic, and magnetic resonance findings in 34 patients with pathologic correlation

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    Collins, Mark S.; Koyama, Takashi; Swee, Ronald G.; Inwards, Carrie Y. [Department of Radiology, Mayo Clinic, 200 First Street SW, MN 55905, Rochester (United States)

    2003-12-01

    To describe the radiographic features of clear cell chondrosarcoma (CCCS), including the computed tomographic (CT) and magnetic resonance (MR) findings, and to correlate them with the histopathologic findings. A retrospective review was carried out of 72 patients with histopathologically confirmed CCCS. Imaging studies were available for 34 patients: conventional radiographs (n=28), CT scans (n=14), and MR images (n=15). Radiographic studies were reviewed by three radiologists who rendered a consensus opinion; the studies were correlated with the histopathologic findings. Of the 34 patients with imaging studies, 30 were male and 4 were female (mean age 38.6 years; range 11-74 years). Twenty-two lesions were in long bones (15, proximal femur; 1, distal femur; 1, proximal tibia; 5, proximal humerus) and 11 were in flat bones (5, vertebra; 4, rib; 1, scapula; 1, innominate). One lesion occurred in the tarsal navicular bone. Typically, long bone lesions were located in the epimetaphysis (19/22) and were lucent with a well-defined sclerotic margin and no cortical destruction or periosteal new bone formation. More than one-third of the long bone lesions contained matrix mineralization with a characteristic chondroid appearance. Pathologic fractures were present in six long bone lesions (4, humerus; 2, femur). Lesions in the proximal humerus were more likely to have indistinct margins (4/5) and extend into the diaphysis. Flat bone lesions were typically lytic and expansile and occasionally demonstrated areas of cortical disruption. Typically, matrix mineralization, when present, was amorphous. MR imaging, when available, was superior to conventional radiographs for demonstrating the intramedullary extent of a lesion as well as soft tissue extension. CT images better delineated the presence of cortical destruction and the character of matrix mineralization patterns. CCCS lesions were typically low signal intensity on T1-weighted images and moderately or significantly

  2. Clear cell chondrosarcoma: radiographic, computed tomographic, and magnetic resonance findings in 34 patients with pathologic correlation

    International Nuclear Information System (INIS)

    Collins, Mark S.; Koyama, Takashi; Swee, Ronald G.; Inwards, Carrie Y.

    2003-01-01

    To describe the radiographic features of clear cell chondrosarcoma (CCCS), including the computed tomographic (CT) and magnetic resonance (MR) findings, and to correlate them with the histopathologic findings. A retrospective review was carried out of 72 patients with histopathologically confirmed CCCS. Imaging studies were available for 34 patients: conventional radiographs (n=28), CT scans (n=14), and MR images (n=15). Radiographic studies were reviewed by three radiologists who rendered a consensus opinion; the studies were correlated with the histopathologic findings. Of the 34 patients with imaging studies, 30 were male and 4 were female (mean age 38.6 years; range 11-74 years). Twenty-two lesions were in long bones (15, proximal femur; 1, distal femur; 1, proximal tibia; 5, proximal humerus) and 11 were in flat bones (5, vertebra; 4, rib; 1, scapula; 1, innominate). One lesion occurred in the tarsal navicular bone. Typically, long bone lesions were located in the epimetaphysis (19/22) and were lucent with a well-defined sclerotic margin and no cortical destruction or periosteal new bone formation. More than one-third of the long bone lesions contained matrix mineralization with a characteristic chondroid appearance. Pathologic fractures were present in six long bone lesions (4, humerus; 2, femur). Lesions in the proximal humerus were more likely to have indistinct margins (4/5) and extend into the diaphysis. Flat bone lesions were typically lytic and expansile and occasionally demonstrated areas of cortical disruption. Typically, matrix mineralization, when present, was amorphous. MR imaging, when available, was superior to conventional radiographs for demonstrating the intramedullary extent of a lesion as well as soft tissue extension. CT images better delineated the presence of cortical destruction and the character of matrix mineralization patterns. CCCS lesions were typically low signal intensity on T1-weighted images and moderately or significantly

  3. A Case of Chondrosarcoma Arising in the Temporomandibular Joint

    Directory of Open Access Journals (Sweden)

    Tsutomu Nomura

    2015-01-01

    Full Text Available Chondrosarcoma is a malignant tumor originating in cartilaginous cells. And there are only few reports of the case of chondrosarcoma in temporomandibular joint. We discuss a case of chondrosarcoma in temporomandibular joint in a 28-year-old man. Tumor was in contact with the dura, but en bloc resection was performed. After surgical resection of the tumor, face defect was reconstructed by rectus abdominis-free flap. And there is no recurrence after ten years from the resection.

  4. Knockdown of long non-coding RNA HOTAIR increases miR-454-3p by targeting Stat3 and Atg12 to inhibit chondrosarcoma growth.

    Science.gov (United States)

    Bao, Xing; Ren, Tingting; Huang, Yi; Sun, Kunkun; Wang, Shidong; Liu, Kuisheng; Zheng, Bingxin; Guo, Wei

    2017-02-09

    Current practices for the therapy of chondrosarcoma, including wide-margin surgical resection and chemotherapy, are less than satisfactory. Recently, emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) have an essential role in the initiation and progression of tumors. As a typical lncRNA, HOTAIR is significantly overexpressed in various tumors. However, the function and potential biological mechanisms of HOTAIR in human chondrosarcoma remain unknown. Quantitative RT-PCR demonstrated that HOTAIR expression was upregulated in chondrosarcoma tissues and cell lines. High HOTAIR expression is correlated with tumor stage and poor prognosis. Functional experiments reveal that HOTAIR knockdown leads to growth inhibition of human chondrosarcoma cells in vitro and in vivo. In addition to cycle arrest and apoptosis, knockdown of HOTAIR inhibits autophagy, which favors cell death. Mechanistically, we demonstrated that HOTAIR induced DNA methylation of miR-454-3p by recruiting EZH2 and DNMT1 to the miR-454-3p promoter regions, which markedly silences miR-454-3p expression. Further analysis revealed that STAT3 and ATG12 are targets of miR-454-3p, initiate HOTAIR deficiency-induced apoptosis and reduce autophagy. Collectively, our data reveal the roles and functional mechanisms of HOTAIR in human chondrosarcoma and suggest that HOTAIR may act as a prognostic biomarker and potential therapeutic target for chondrosarcoma.

  5. Chondrosarcoma of the Heart

    Directory of Open Access Journals (Sweden)

    Do Jung Kim

    2015-06-01

    Full Text Available Chondrosarcoma is a rare entity of malignant tumor which arises from cartilaginous tissue, and the literatures on this disease are scarce. The first-line of treatment for cardiac chondrosarcoma is surgery. Due to early local recurrence and distant metastasis, the prognosis is poor even after complete surgical excision. We present a case of chondrosarcoma in the left atrium causing functional mitral stenosis which required urgent surgical intervention, and the successful treatment outcome.

  6. Myxoid Chondrosarcoma of the Sinonasal Cavity in a Child: a Case Report

    International Nuclear Information System (INIS)

    Kim, Yeo Ju; Im, Soo Ah; Lim, Gye Yeon; Chun, Ho Jong; Park, Hyun Jin; Kim, Min Sik; Choi, Yeong Jin

    2007-01-01

    Chondrosarcomas are malignant tumors of cartilage that rarely involve the sinonasal region, and myxoid chondrosarcoma is a rare histologic variant of chondrosarcoma that usually occurs in the soft tissue of extremities. Although several case reports and results of small series of chondrosarcomas in the sinonasal region in children are available, myxoid type chondrosarcoma is extremely rare. We recently experienced a case of low grade myxoid chondrosarcoma involving the sinonasal cavity in a 10-year-old boy, and here we report its radiologic-pathologic findings. In this case, chondroid calcification on CT and septal and marginal enhancement on MRI suggested a chondrosarcoma. Whole body PET-CT demonstrated no definite metastatic lesion and a low peak standardized uptake value primary tumor. However, no definite distinguishing imaging features were observed that distinguished low grade myxoid chondrosarcoma from conventional chondrosarcoma. hondrosarcomas are malignant mesenchymal tumors of cartilage, and usually involve the long bone and pelvis. Less than 10% of chondrosarcomas are found in the head and neck region. Chondrosarcomas can occur at any age, but the majority present between the 5th and 7th decades. Therefore, chondrosarcomas of the head and neck in children are rare; only about 13 cases of sinonasal chondrosarcoma in children have been reported. Myxoid chondrosarcoma is a rare histologic variant of chondrosarcoma, and is characterized by abundant chondroid matrix and malignant chondroblastic cells arranged in cords resembling chordoma. Myxoid chondrosarcomas are typically located in the limbs in older patients, and only rarely originate in the head and neck in children. To the best of our knowledge, only one case report of myxoid type chondrosarcoma in the sinonasal region in a child is available. We report a case of myxoid chondrosarcoma involving the sinonasal cavity in a child and describe its computed tomography (CT), magnetic resonance imaging (MRI

  7. Myxoid Chondrosarcoma of the Sinonasal Cavity in a Child: a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yeo Ju; Im, Soo Ah; Lim, Gye Yeon; Chun, Ho Jong; Park, Hyun Jin; Kim, Min Sik; Choi, Yeong Jin [The Catholic University of Korea, Seoul (Korea, Republic of)

    2007-10-15

    Chondrosarcomas are malignant tumors of cartilage that rarely involve the sinonasal region, and myxoid chondrosarcoma is a rare histologic variant of chondrosarcoma that usually occurs in the soft tissue of extremities. Although several case reports and results of small series of chondrosarcomas in the sinonasal region in children are available, myxoid type chondrosarcoma is extremely rare. We recently experienced a case of low grade myxoid chondrosarcoma involving the sinonasal cavity in a 10-year-old boy, and here we report its radiologic-pathologic findings. In this case, chondroid calcification on CT and septal and marginal enhancement on MRI suggested a chondrosarcoma. Whole body PET-CT demonstrated no definite metastatic lesion and a low peak standardized uptake value primary tumor. However, no definite distinguishing imaging features were observed that distinguished low grade myxoid chondrosarcoma from conventional chondrosarcoma. hondrosarcomas are malignant mesenchymal tumors of cartilage, and usually involve the long bone and pelvis. Less than 10% of chondrosarcomas are found in the head and neck region. Chondrosarcomas can occur at any age, but the majority present between the 5th and 7th decades. Therefore, chondrosarcomas of the head and neck in children are rare; only about 13 cases of sinonasal chondrosarcoma in children have been reported. Myxoid chondrosarcoma is a rare histologic variant of chondrosarcoma, and is characterized by abundant chondroid matrix and malignant chondroblastic cells arranged in cords resembling chordoma. Myxoid chondrosarcomas are typically located in the limbs in older patients, and only rarely originate in the head and neck in children. To the best of our knowledge, only one case report of myxoid type chondrosarcoma in the sinonasal region in a child is available. We report a case of myxoid chondrosarcoma involving the sinonasal cavity in a child and describe its computed tomography (CT), magnetic resonance imaging (MRI

  8. Intracortical chondrosarcoma: a case report.

    Directory of Open Access Journals (Sweden)

    Khodamorad Jamshidi

    2014-02-01

    Full Text Available Chondrosarcoma is the second most common primary mesenchymal malignant tumor of the bone. The most common form is central chondrosarcoma and the rarest is intracortical chondrosarcoma. Here, we describe the clinical, pathological, and imaging features of a case of intracortical chondrosarcoma as well as the outcome of surgical treatment. This is the third case reported in the literature.

  9. Intracortical chondrosarcoma: a case report.

    OpenAIRE

    Khodamorad Jamshidi; Reza Razavi; Homan Yahyazadeh

    2014-01-01

    Chondrosarcoma is the second most common primary mesenchymal malignant tumor of the bone. The most common form is central chondrosarcoma and the rarest is intracortical chondrosarcoma. Here, we describe the clinical, pathological, and imaging features of a case of intracortical chondrosarcoma as well as the outcome of surgical treatment. This is the third case reported in the literature.

  10. Acral synovial chondrosarcoma

    International Nuclear Information System (INIS)

    Wenger, D.E.; Sundaram, M.; Unni, K.K.; Janney, C.G.; Merkel, K.

    2002-01-01

    Acral chondrosarcoma is rare. Synovial chondrosarcoma is even rarer. Synovial chondrosarcoma arising without evidence of pre-existing or concurrent synovial chondromatosis is exceedingly rare. We present a case of acral synovial chondrosarcoma involving both sides of the metacarpophalangeal joint of the thumb in a 69-year-old man. Radiographically, the lesion mimicked gout. On MR imaging, the lobulated contours of the soft tissue mass suggested synovial chondromatosis. Histological examination revealed a chondrosarcoma, which on the basis of imaging findings we present as having arisen from the synovium. The tumor invaded a portion of the cartilage of the metacarpophalangeal joint and equally destroyed the bones of the distal metacarpal and base of the proximal phalanx of the thumb, while sparing the bony joint surfaces. (orig.)

  11. Irregular radiation response of a chondrosarcoma

    International Nuclear Information System (INIS)

    Marsden, J.J.; Kember, N.F.; Shaw, J.E.H.

    1980-01-01

    The DC II mouse chondrosarcoma was shown to be a potentially valuable radiobiological tumour system since it recovered from radiation injury by regrowth from clones that could be counted in histological sections. Unfortunately, the normal growth of this tumour following s.c. implantation in the thigh was irregular both in the time before growth became evident and in the rate of growth. The response to radiation was also unreliable since tumours irradiated with the same dose (e.g. 30 Gy) showed a range of responses from shrinkage to no detectable change in growth rate. The delay in normal growth can be attributed largely to delays in vascularization while changes in growth rate may be explained by differences in tumour architecture. Radiation response may depend on variations in hypoxic fraction and in relative cellularity. Tumours having the same external dimensions may differ by a factor of 80 in the numbers of tumour cells they contain. This chondrosarcoma may prove a closer model to some human tumours than many transplantable tumours that display regular growth patterns. (author)

  12. Clinical benefit of antiangiogenic therapy in advanced and metastatic chondrosarcoma.

    Science.gov (United States)

    Jones, Robin L; Katz, Daniela; Loggers, Elizabeth T; Davidson, Darin; Rodler, Eve T; Pollack, Seth M

    2017-08-29

    Chondrosarcoma is the most common bone sarcoma in adults. Conventional chondrosarcoma, the commonest histological subtype, is largely resistant to anthracycline-based chemotherapy. There have been anecdotal reports of durable clinical benefit with antiangiogenic agents in this disease. A retrospective search of patients treated at three sarcoma referral centers was performed to identify patients with advanced chondrosarcoma treated with antiangiogenic agents. The aim of this study was to evaluate the efficacy and safety of antiangiogenic agents in advanced chondrosarcoma. Ten patients were identified; seven with conventional, one each with clear cell, extraskeletal mesenchymal chondrosarcoma and extraskeletal myxoid chondrosarcoma. The median progression-free survival for patients with conventional and clear cell sarcoma was 22.6 months. Median overall survival has not been met. Antiangiogenic therapy was well tolerated in this series of patients. Our retrospective data suggest that antiangiogenic therapy can provide prolonged clinical benefit in advanced chondrosarcoma patients. Further prospective trials are required to precisely define the role of this class of agent in advanced chondrosarcoma.

  13. Sphingosine-1-phosphate suppresses chondrosarcoma metastasis by upregulation of tissue inhibitor of metalloproteinase 3 through suppressing miR-101 expression.

    Science.gov (United States)

    Tsai, Chun-Hao; Yang, Dong-Ying; Lin, Chih-Yang; Chen, Tsung-Ming; Tang, Chih-Hsin; Huang, Yuan-Li

    2017-10-01

    Chondrosarcoma is the second most common primary malignancy form of bone cancer, exhibiting resistance to chemotherapy and radiation therapy as well as developing high metastasis ability in late-stage tumors. Thus, understanding the metastatic processes of chondrosarcoma is considered a strategy for the treatment of this disease. Sphingosine 1-phosphate (S1P), a bioactive sphingolipid, is produced intracellularly by sphingosine kinase (SphK) and is regarded as a second signaling molecule that regulates inflammation, proliferation, angiogenesis, and metastasis. However, the effect of S1P on chondrosarcoma remains uncertain. As demonstrated by the transwell, immunoblotting, and real-time PCR analyses, we found that S1P inhibited cell migration and MMP-2 expression through the upregulation of the tissue inhibitor of metalloproteinase-3 (TIMP-3) expression in human chondrosarcoma cells. Additionally, we also showed that microRNA (miRNA)-101, which targets the 3' untranslated region (3'UTR) of TIMP-3, decreased significantly following S1P treatment. After transfection with miR-101 mimics, the S1P-regulated cell migration and TIMP-3 expression were both reversed. Furthermore, we also showed that the S1P-inhibited cell migration is mediated through the c-Src/MEK/ERK signaling axis. Meanwhile, the in vivo study indicated that overexpression of SphK1 decreases chondrosarcoma metastasis to the lungs. Our results illustrate the clinical significance between SphK1, TIMP-3, and miR-101 in human chondrosarcoma patients. Taken together, our results suggest that S1P and miR-101 may prove to be potential therapeutic targets for future chondrosarcoma treatment. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  14. Transarticular extension of chondrosarcoma

    International Nuclear Information System (INIS)

    Pinstein, M.L.; Sebes, J.I.; Scott, R.L.

    1984-01-01

    Chondrosarcoma is the third most common primary malignant tumor of bone. Epiphyseal invasion is rare and joint involvement is reported to be even less common. In this paper, a patient is described with primary medullary chondrosarcoma of the proximal tibia with transarticular spread of the tumor to involve the distal femur. The differential diagnosis with bone scans and CT and the possible mechanisms of transarticular spread are discussed

  15. Bladder chondrosarcoma plus urothelial carcinoma in recurred transitional cell carcinoma of the upper urinary tract: a case report and literature review.

    Science.gov (United States)

    Cho, Min Hyun; Kim, Sung Han; Park, Weon Seo; Joung, Jae Young; Seo, Ho Kyung; Chung, Jinsoo; Lee, Kang Hyun

    2016-10-20

    Sarcomatoid urothelial carcinoma (SUC) is a rare malignant neoplasm of the urinary bladder comprising 0.2-0.6 % of all histological bladder tumor subtypes. It presents as a high-stage malignancy and exhibits aggressive biological behavior, regardless of the treatment employed. It is defined as histologically indistinguishable from sarcoma and as a high-grade biphasic neoplasm with malignant epithelial and mesenchymal components. The mean age of patients presenting with SUC is 66 years, and the male-to-female ratio is 3:1. In addition, gross hematuria is usually present. The prognosis of SUC is poorer than that of typical urothelial carcinoma because of uncertainty concerning the optimal treatment regimen. We report the case of a 77-year-old woman with SUC containing a chondrosarcoma component who, 12 years previously, had undergone a nephroureterectomy for pT3N0M0 ureter cancer of the contralateral upper urinary tract. From the 4th year of follow-up after nephroureterectomy, multiple recurrent bladder tumors staged as Ta transitional cell carcinoma developed, and six transurethral resections of the bladder (TURB) with multiple intravesical instillations were performed without any evidence of metastases and upper tract recurrences. In 2015, a right partial distal ureterectomy and an additional TURB were performed due to a papillary mass at the right contralateral ureterovesical junction of the bladder, which was confirmed as a high-grade pT1 transitional cell carcinoma. After a further 2 years of follow-up, total pelvic exenteration with an ileal conduit diversion was performed to remove the mass, which was a pT4N0M0 tumor composed of carcinomatous and sarcomatous elements compatible with a sarcomatoid carcinoma including grade 3 transitional cell carcinoma and chondrosarcoma. Immunohistochemical examination showed that tumor cells were positive for vimentin and p63 and negative for NSE and Cd56 markers. In the first postoperative month, a metastatic lung nodule

  16. Larynx mixoid chondrosarcoma

    International Nuclear Information System (INIS)

    Bautista Robalino, A.; Reyes Karolys, D.; Torres Freire, C.

    2006-01-01

    Laryngeal chondrosarcoma constitutes a malignant neoplasm of cartilaginous origin. The most frequently localization is at the cricoid cartilage, it is rarely seen at the thyroid or arytenoid cartilage. The late apparition of the symptoms delays the diagnosis which is orientated by image studies and will be confirmed by histopathological analysis of the surgical specimen. The biological behavior is characterized by loco regional recurrence in direct correlation with the grade of surgery is the elective treatment. The present case is a larynx mixoid chondrosarcoma of the vocal cord. (The author)

  17. Targeting survivin as a potential new treatment for chondrosarcoma of bone

    Science.gov (United States)

    de Jong, Y; van Oosterwijk, J G; Kruisselbrink, A B; Briaire-de Bruijn, I H; Agrogiannis, G; Baranski, Z; Cleven, A H G; Cleton-Jansen, A-M; van de Water, B; Danen, E H J; Bovée, J V M G

    2016-01-01

    Chondrosarcomas are malignant cartilage-forming bone tumors, which are intrinsically resistant to chemo- and radiotherapy, leaving surgical removal as the only curative treatment option. Therefore, our aim was to identify genes involved in chondrosarcoma cell survival that could serve as a target for therapy. siRNA screening for 51 apoptosis-related genes in JJ012 chondrosarcoma cells identified BIRC5, encoding survivin, as essential for chondrosarcoma survival. Using immunohistochemistry, nuclear as well as cytoplasmic survivin expression was analyzed in 207 chondrosarcomas of different subtypes. Nuclear survivin has been implicated in cell-cycle regulation while cytoplasmic localization is important for its anti-apoptotic function. RT–PCR was performed to determine expression of the most common survivin isoforms. Sensitivity to YM155, a survivin inhibitor currently in phase I/II clinical trial for other tumors, was examined in 10 chondrosarcoma cell lines using viability assay, apoptosis assay and cell-cycle analysis. Survivin expression was found in all chondrosarcoma patient samples. Higher expression of nuclear and cytoplasmic survivin was observed with increasing histological grade in central chondrosarcomas. Inhibition of survivin using YM155 showed that especially TP53 mutant cell lines were sensitive, but no caspase 3/7 or PARP cleavage was observed. Rather, YM155 treatment resulted in a block in S phase in two out of three chondrosarcoma cell lines, indicating that survivin is more involved in cell-cycle regulation than in apoptosis. Thus, survivin is important for chondrosarcoma survival and chondrosarcoma patients might benefit from survivin inhibition using YM155, for which TP53 mutational status can serve as a predictive biomarker. PMID:27159675

  18. A case of dedifferentiated chondrosarcoma arising in the cricoid cartilage that mimicked an aneurysmal bone cyst.

    Science.gov (United States)

    Chen, Lixiao; Yu, Ziwei; Jiang, Rui; Dong, Pin; Shen, Bin; Li, Yu

    2018-03-01

    Dedifferentiated chondrosarcoma of the larynx is a rare and highly malignant tumor. We present the report of a 59-year-old man with dedifferentiated laryngeal chondrosarcoma, which was difficult to diagnose even under microscopic examination. The original diagnosis was an aneurysmal bone cyst, and the final diagnosis was established only after careful consideration of the imaging, surgical, and microscopic findings. In clinical practice, there are many similarities between dedifferentiated chondrosarcoma and aneurysmal bone cysts. Furthermore, it is difficult to identify dedifferentiated laryngeal chondrosarcoma with a giant-cell malignant mesenchymal component. This report describes our experience and discusses this phenomenon.

  19. Osteoclast inhibition impairs chondrosarcoma growth and bone destruction.

    Science.gov (United States)

    Otero, Jesse E; Stevens, Jeff W; Malandra, Allison E; Fredericks, Douglas C; Odgren, Paul R; Buckwalter, Joseph A; Morcuende, Jose

    2014-12-01

    Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone histologically and radiographically for bone destruction and tumor growth. At three weeks, tumors invaded local bone causing cortical disruption and trabecular resorption. Bone destruction was accompanied by increased osteoclast number and resorbed bone surface. Treatment of rats with the zoledronic acid prevented cortical destruction, inhibited trabecular resorption, and resulted in decreased tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not off-target effects of drug, was responsible for the prevention of tumor growth and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced bone destruction and tumor growth were impaired in osteopetrotic bone compared with control bone. The results from our animal model demonstrate that osteoclasts contribute to chondrosarcoma-mediated bone destruction and tumor growth and may represent a therapeutic target in particular chondrosarcoma patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  20. Regulation of collagenase inhibitor production in chondrosarcoma chondrocytes

    International Nuclear Information System (INIS)

    Harper, J.; Harper, E.

    1987-01-01

    Swarm rat chondrosarcoma chondrocytes produce an inhibitor of collagenase. This inhibitor is similar to those isolated from normal cartilage tissues. These cells will synthesize proteins in the absence of serum. Since serum contains inhibitors of collagenase, it is necessary to culture cells without serum in order to obtain accurate measurements of enzyme and inhibitor levels. They examined the effect of insulin on inhibitor secretion by cultures of Swarm rat chondrosarcoma chondrocytes. They observed a 2.5 to 3.5 fold stimulation of inhibitory activity in the presence of as little as 10 ng/ml insulin as compared to controls in serum free Dulbecco's modified Eagle's medium supplemented with 4.5 g/l glucose. The units of inhibitor were determined over a 7 day culture period. Medium was harvested daily and assayed for collagenase activity and for inhibition of a known collagenase from rabbit skin or human skin, using the 14 C-glycine peptide release assay. The amount of inhibitor obtained from days 2 through 7 were: 1.4 unit (control), 3.8 units (10 ng/ml insulin), 5.2 units (1 μg/ml insulin). The addition of 1 mM dibutyryl cyclic AMP to these chondrocytes in the presence of 1 μg/ml insulin caused a decrease in the level of inhibitor, suggesting that a dephosphorylation event may be necessary for this stimulation by insulin to occur

  1. Chondrosarcoma of a thoracic vertebra

    International Nuclear Information System (INIS)

    Abdelwahab, I.F.; Casden, A.M.; Klein, M.J.; Spollman, A.

    1991-01-01

    Central chondrosarcoma is an uncommon primary malignancy of the axial skeleton which usually affects the posterior elements or the posterior part of a vertebral body. The authors present an unusual case of chondrosarcoma involving the anterior part of a thoracic vertebra with massive extravertebral extension into the posterior mediastinum. The roles of computed tomography and magnetic resonance imaging in identifying this pathology are emphasized

  2. Novel therapeutic approaches in chondrosarcoma.

    Science.gov (United States)

    Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M; Huang, Paul H; Lee, Alex; Jones, Robin L

    2017-03-01

    Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

  3. X-ray diagnosis of rib chondrosarcoma

    International Nuclear Information System (INIS)

    Smakova, M.S.

    1982-01-01

    A study was made on X-ray images of 24 patients, suffering from rib chondrosarcoma with relapses. X-ray symptoms of rib chondrosarcoma, depending on process localization were improved. Chondrosarcoma of rib cartilage is characterized by soft-tissue component with calcareous inclusions or without them. Chondrosarcoma of rib bone is characterized by destruction and soft-tissue component. Chondrosarcoma relapses were localized in soft tissues

  4. Functional roles of CSPG4/NG2 in chondrosarcoma.

    Science.gov (United States)

    Jamil, Nuor S M; Azfer, Asim; Worrell, Harrison; Salter, Donald M

    2016-04-01

    CSPG4/NG2 is a multifunctional transmembrane protein with limited distribution in adult tissues including articular cartilage. The purpose of this study was to investigate the possible roles of CSPG4/NG2 in chondrosarcomas and to establish whether this molecule may have potential for targeted therapy. Stable knock-down of CSPG4/NG2 in the JJ012 chondrosarcoma cell line by shRNA resulted in decreased cell proliferation and migration as well as a decrease in gene expression of the MMP (matrix metalloproteinase) 3 protease and ADAMTS4 (aggrecanase). Chondrosarcoma cells in which CSPG4/NG2 was knocked down were more sensitive to doxorubicin than wild-type cells. The results indicate that CSPG4/NG2 has roles in regulating chondrosarcoma cell function in relation to growth, spread and resistance to chemotherapy and that anti-CSPG4/NG2 therapies may have potential in the treatment of surgically unresectable chondrosarcoma. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  5. Expression of MMPs is dependent on the activity of mitogen-activated protein kinase in chondrosarcoma.

    Science.gov (United States)

    Yao, Min; Wang, Xiaomei; Zhao, Yufeng; Wang, Xiaomeng; Gao, Feng

    2017-02-01

    Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) serve an important role in chondrosarcoma. The present study investigated whether the expression of MMPs was dependent on the activity of mitogen-activated protein kinase (MAPK) in chondrosarcoma. Surgical pathological specimens were collected to detect MMP-1, MMP-13, TIMP-1, type II collagen and phosphorylated MAPK levels in normal cartilage, enchondroma and chondrosarcoma tissues. The expression of MMP‑1, MMP‑13, TIMP‑1 and type II collagen was investigated utilizing MAPK inhibitors in chondrosarcoma cells. It was noted that the expression levels of MMP‑1, MMP‑13 and TIMP‑1 were increased in chondrosarcoma with the activity of MAPK. After chondrosarcoma cells were pretreated with MAPK inhibitors, the levels of MMP‑1, MMP‑13 and TIMP‑1 were inhibited. Furthermore, MMP‑1 and MMP‑13 are essential in regulating the degradation of type II collagen and decomposing cartilage matrix major. The high expression levels of MMP‑1 and MMP‑13 in chondrosarcoma expedite the invasion by chondrosarcoma cells and their expression can be depressed by MAPK inhibitors.

  6. No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone

    International Nuclear Information System (INIS)

    Peterse, Elisabeth F. P.; Cleven, Arjen H. G.; De Jong, Yvonne; Briaire-de Bruijn, Inge; Fletcher, Jonathan A.; Danen, Erik H. J.; Cleton-Jansen, Anne-Marie; Bovée, Judith V. M. G.

    2016-01-01

    Chondrosarcoma is a malignant cartilage forming bone tumour for which no effective systemic treatment is available. Previous studies illustrate the need for a better understanding of the role of the IGF pathway in chondrosarcoma to determine if it can be a target for therapy, which was therefore explored in this study. Expression of mediators of IGF1R signalling and phosphorylation status of IRS1 was determined in chondrosarcoma cell lines by qRT-PCR and western blot. The effect of activation and inhibition of IGF1R signalling on downstream targets was assessed by western blot. Ten chondrosarcoma cell lines were treated with OSI-906 (IGF1R and IR dual inhibitor) after which cell proliferation and migration were determined by a viability assay and the xCELLigence system, respectively. In addition, four chondrosarcoma cell lines were treated with a combination of doxorubicin and OSI-906. By immunohistochemistry, IGF1R expression levels were determined in tissue microarrays of 187 cartilage tumours and ten paraffin embedded cell lines. Mediators of IGF1R signalling are heterogeneously expressed and phosphorylated IRS1 was detected in 67 % of the tested chondrosarcoma cell lines, suggesting that IGF1R signalling is active in a subset of chondrosarcoma cell lines. In the cell lines with phosphorylated IRS1, inhibition of IGF1R signalling decreased phosphorylated Akt levels and increased IGF1R expression, but it did not influence MAPK or S6 activity. In line with these findings, treatment with IGF1R/IR inhibitors did not impact proliferation or migration in any of the chondrosarcoma cell lines, even upon stimulation with IGF1. Although synergistic effects of IGF1R/IR inhibition with doxorubicin are described for other cancers, our results demonstrate that this was not the case for chondrosarcoma. In addition, we found minimal IGF1R expression in primary tumours in contrast to the high expression detected in chondrosarcoma cell lines, even if both were derived from the

  7. No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone.

    Science.gov (United States)

    Peterse, Elisabeth F P; Cleven, Arjen H G; De Jong, Yvonne; Briaire-de Bruijn, Inge; Fletcher, Jonathan A; Danen, Erik H J; Cleton-Jansen, Anne-Marie; Bovée, Judith V M G

    2016-07-14

    Chondrosarcoma is a malignant cartilage forming bone tumour for which no effective systemic treatment is available. Previous studies illustrate the need for a better understanding of the role of the IGF pathway in chondrosarcoma to determine if it can be a target for therapy, which was therefore explored in this study. Expression of mediators of IGF1R signalling and phosphorylation status of IRS1 was determined in chondrosarcoma cell lines by qRT-PCR and western blot. The effect of activation and inhibition of IGF1R signalling on downstream targets was assessed by western blot. Ten chondrosarcoma cell lines were treated with OSI-906 (IGF1R and IR dual inhibitor) after which cell proliferation and migration were determined by a viability assay and the xCELLigence system, respectively. In addition, four chondrosarcoma cell lines were treated with a combination of doxorubicin and OSI-906. By immunohistochemistry, IGF1R expression levels were determined in tissue microarrays of 187 cartilage tumours and ten paraffin embedded cell lines. Mediators of IGF1R signalling are heterogeneously expressed and phosphorylated IRS1 was detected in 67 % of the tested chondrosarcoma cell lines, suggesting that IGF1R signalling is active in a subset of chondrosarcoma cell lines. In the cell lines with phosphorylated IRS1, inhibition of IGF1R signalling decreased phosphorylated Akt levels and increased IGF1R expression, but it did not influence MAPK or S6 activity. In line with these findings, treatment with IGF1R/IR inhibitors did not impact proliferation or migration in any of the chondrosarcoma cell lines, even upon stimulation with IGF1. Although synergistic effects of IGF1R/IR inhibition with doxorubicin are described for other cancers, our results demonstrate that this was not the case for chondrosarcoma. In addition, we found minimal IGF1R expression in primary tumours in contrast to the high expression detected in chondrosarcoma cell lines, even if both were derived from the

  8. Management of pelvic chondrosarcoma

    Directory of Open Access Journals (Sweden)

    Florin Groșeanu

    2016-11-01

    Full Text Available The partial or complete excision of the hemipelvis with sparing of the lower limb is an option of the treatment of pelvic chondrosarcoma and a therapeutic alternative of the interilio-abdominal disarticulation. The operation has in principle the same indications as the interilio-abdominal disarticulation and offers a good solution for avoiding a mutilating operation. The 149 cases include: 120 biopsies, 29 excisional biopsies, 6 interilioabdominal disarticulations and 14 resections – reconstruction’s, one of with prosthetic reconstruction. The prognostic score was established by assessing: the surgical stage, the site of the tumor, the surgical margins of the tumor, the functional mobility and the postoperative activity. The wide excision of the tumor, a stable reconstruction and an efficient recovery are essential for a successful treatment of pelvic chondrosarcoma. The limb sparing resection-reconstruction represents a highly surgical demanding procedure, followed up by complications in 60% of the cases, so that should be performed only by high skilled surgeons. Hemipelvectomy still remains a well-established life-saving surgery method for patients suffering from vast oncological extensions, where a pelvic resection is not an option.

  9. Intracardiac metastasis originated from chondrosarcoma.

    Science.gov (United States)

    Maurea, Nicola; Ragone, Gianluca; Coppola, Carmela; Caronna, Antonietta; Tocchetti, Carlo G; Agozzino, Lucio; Apice, Gaetano; Iaffaioli, Rosario V

    2017-05-01

    Primary cardiac tumors are extremely rare. By comparison, metastatic involvement of the heart is over 20 times more common and has been reported in autopsy series in up to one in five patients dying of cancer. Cardiac metastasis of chondrosarcoma is absolutely not frequent. In the recent literature, a cardiac metastasis from chondrosarcoma has never been described. We report the case of an 18-year-old man with a diagnosis of cardiac metastasis that originated from a left scapular chondrosarcoma. Chondrosarcoma is a skeletal tumor with various grades of malignancy, rapidly evolving, and with a strong tendency to metastasize, with low responsiveness to chemotherapy. The onset of characteristic systemic symptoms in the late stage of the disease led to the diagnosis of a mass localized in the right atrium. Management and differential diagnosis of infective heart lesions were also very complex in a rapidly evolving life-threatening condition.

  10. Chondrosarcoma in Hereditary Multiple Exostosis

    African Journals Online (AJOL)

    1974-04-06

    Apr 6, 1974 ... The other bones in the amputated limb were studded with typical benign ... exostosis is uncertain, while the histological diagnosis of a chondrosarcoma .... intervals for radiographic examination of this lesion. Two years later ...

  11. Immunolocalization of notch signaling protein molecules in a maxillary chondrosarcoma and its recurrent tumor

    Directory of Open Access Journals (Sweden)

    Siar CH

    2010-10-01

    Full Text Available Abstract Background Notch receptors are critical determinants of cell fate in a variety of organisms. Notch signaling is involved in the chondrogenic specification of neural crest cells. Aberrant Notch activity has been implicated in numerous human diseases including cancers; however its role in chondrogenic tumors has not been clarified. Method Tissue samples from a case of primary chondrosarcoma of the maxilla and its recurrent tumor were examined immunohistochemically for Notch1-4 and their ligands (Jagged1, Jagged2 and Delta1 expression. Results Both primary and recurrent tumors were histopathologically diagnosed as conventional hyaline chondrosarcoma (WHO Grade I. Hypercellular tumor areas strongly expressed Notch3 and Jagged1 in spindle and pleomorphic cells suggesting up-regulation of these protein molecules at sites of tumor proliferation. Expression patterns were distinct with some overlap. Differentiated malignant and atypical chondrocytes demonstrated variable expression levels of Jagged1, and weak to absent staining for Notch1, 4 and Delta1. Protein immunolocalization was largely membranous and cytoplasmic, sometimes outlining the lacunae of malignant chondrocytes. Hyaline cartilage demonstrated a diffuse or granular precipitation of Jagged1 suggesting presence of soluble Jagged1 activity at sites of abnormal chondrogenesis. No immunoreactivity for the other Notch members was observed. Calcified cartilage was consistently Notch-negative indicating down-regulation of Notch with cartilage maturation. Stromal components namely endothelial cells and fibroblasts variably expressed Notch1, 3 and Jagged1 but were mildly or non-reactive for the other members. Conclusions Results indicate that Notch signaling pathway may participate in cellular differentiation and proliferation in chondrosarcoma. Findings implicate Notch3 and Jagged1 as key molecules that influence the differentiation and maturation of cells of chondrogenic lineage.

  12. Primary intraocular chondrosarcoma in a dog

    Directory of Open Access Journals (Sweden)

    E. Perlmann

    2013-12-01

    Full Text Available A five-year-old male Cocker Spaniel was presented for evaluation of the right eye due to discomfort, abundant purulent discharge and progressive enlargement of the eyeball. The owner revealed that the right eye has appeared to be inflamed and smaller then the left eye for years. Ophthalmic examination revealed corneal perforation, buphthalmia and conjuctival hyperemia. Enucleating was performed due to signs of endophthalmitis and ocular discomfort. Histopathology revealed a multilobulated proliferation of chondrocytes producing hyaline cartilage with occasional pleomorphism and binucleate cells. A diagnosis of primary intraocular chondrosarcoma was done.

  13. Radiotherapy of chondrosarcoma of bone

    International Nuclear Information System (INIS)

    Harwood, A.R.; Krajbich, J.I.; Fornasier, V.L.

    1980-01-01

    A retrospective analysis of 31 cases of chondrosarcoma of bone treated by radiotherapy is presented. In comparison with other large series, our group of patients were found to have been unfavourably selected with respect to the known prognostic factors: histology site, adequacy of operative treatment, and presenting symptoms. Twelve patients with primary chondrosarcoma were radically irradiated; 6 of these 12 have been alive and well without tumor for periods ranging from three and a half to 16 years and 3 of these are alive and well for 15 years or more following radiotherapy. The other 6 patients responded or desease stabilized following radiotherapy for periods ranging from 16 months to eight years. One poorly differentiated tumor was radically irradiated and did not respond. Eleven patients were irradiated palliatively, generally with low doses of irradiation, and only 4 responded transiently for periods ranging from three to 12 months. Seven patients with mesenchymal and dedifferentiated tumors were radically irradiated. Four responded or disease stabilized, and 1 of these patients was alive and well at 3 years; 3 did not respond. Six died with distant metastasis. It is concluded that chondrosarcoma of bone is a radioresponsive tumor and the place of radiotherapy in the treatment of this disease and the reason for its being labelled a radioresistant tumor are discussed. The problems of assessing response of chondrosarcoma to therapy are also discussed. It is suggested that chemotherapy may have a role in the management of mesenchymal and dedifferentiated chondrosarcoma

  14. Central nervous system mesenchymal chondrosarcoma

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    Salvati, M.; Frati, A.; Piccirilli, M.; Agrillo, A.; Brogna, C.; Occhiogrosso, G.; Giangaspero, F. [INM Neuromed IRCCS, Pozzilli (Italy). Dept. of Neurosurgery; Caroli, E. [Policlinico S. Andrea, Rome (Italy). Dept. of Neurological Sciences, Neurosurgery

    2005-06-15

    Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

  15. Central nervous system mesenchymal chondrosarcoma

    International Nuclear Information System (INIS)

    Salvati, M.; Frati, A.; Piccirilli, M.; Agrillo, A.; Brogna, C.; Occhiogrosso, G.; Giangaspero, F.; Caroli, E.

    2005-01-01

    Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival

  16. Chondrosarcoma of the Mobile Spine and Sacrum

    Directory of Open Access Journals (Sweden)

    Ryan M. Stuckey

    2011-01-01

    Full Text Available Chondrosarcoma is a rare malignant tumor of bone. This family of tumors can be primary malignant tumors or a secondary malignant transformation of an underlying benign cartilage tumor. Pain is often the initial presenting complaint when chondrosarcoma involves the spine. In the mobile spine, chondrosarcoma commonly presents within the vertebral body and shows a predilection for the thoracic spine. Due to the resistance of chondrosarcoma to both radiation and chemotherapy, treatment is focused on surgery. With en bloc excision of chondrosarcoma of the mobile spine and sacrum patients can have local recurrence rates as low as 20%.

  17. Imaging analysis of dedifferentiated chondrosarcoma of bone

    International Nuclear Information System (INIS)

    Xie Yuanzhong; Kong Qingkui; Wang Xia; Li Changqing

    2004-01-01

    Objective: To analyze the radiological findings of dedifferentiated chondrosarcoma, and to explore the imaging features of dedifferentiated tissue. Methods: The X-ray and CT findings of 13 cases with dedifferentiated chondrosarcoma of bone were analyzed retrospectively, and studied with clinic and corresponding histological changes. Results: The dedifferentiated chondrosarcoma not only had the radiological findings of typical chondrosarcoma but also had the imaging features of dedifferentiated tissues. In 13 patients, periosteal reactions were found in 11 cases, ossifications in 8 cases, soft tissue masses in 12 cases, calcifications in 10 cases, and the site of calcifications in 8 cases was in the center of the focus. Conclusion: The dedifferentiated chondrosarcoma showed special imaging features, which includes ossification, calcification, periosteal reaction, and soft tissue mass. These features were not found in typical chondrosarcoma. Recognizing these specific features is helpful to the diagnosis of dedifferentiated chondrosarcoma. (author)

  18. BH3 mimetics inhibit growth of chondrosarcoma--a novel targeted-therapy for candidate models.

    Science.gov (United States)

    Morii, Takeshi; Ohtsuka, Kouki; Ohnishi, Hiroaki; Mochizuki, Kazuo; Yoshiyama, Akira; Aoyagi, Takayuki; Hornicek, Francis J; Ichimura, Shoichi

    2014-11-01

    Chondrosarcoma is refractory to conventional chemotherapy. BH-3 mimetics ABT-737 and ABT-263 are synthetic small-molecule inhibitors of anti-apoptotic proteins B-cell lymphoma-2 (Bcl2) and Bcl-xL, which play a critical role in survival of chondrosarcoma cells. Chondrosarcoma cell lines SW-1353 and CS-1 were used as the disease model. We used immunoblotting to assess the expression of target molecules Bcl2 and Bcl-xL, and the apoptotic inducers Bcl2-associated X (Bax) and Bcl2-antagonist/killer (Bak). In vitro growth inhibition by BH-3 mimetics was confirmed by photomicroscopic cell counting and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Apoptotic induction was confirmed by Enzyme-Linked ImmunoSorbent Assay (ELISA). In vivo growth inhibition was assessed in a non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse model. Expression of the target and effector molecules was confirmed in chondrosarcoma cell lines. BH3 mimetics significantly inhibited cell growth and induced apoptosis in vitro. Administration of ABT-263 inhibited chondrosarcoma growth and improved survival in a mouse model. BH3 mimetics represent a novel treatment modality for chondrosarcoma. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Myxoid chondrosarcoma of sphenoid bone

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    Amit K Chowhan

    2012-01-01

    Full Text Available The myxoid variant of chondrosarcoma is usually seen in soft tissues where it is known as chordoid sarcoma or parachordoma. Rarely, it involves bone and when it does, cranial bones are the preferred location. This tumor is frequently amalgamated with the chondroid variant of chordoma, especially when the lesion occurs in the sphenoid bone/spheno-occipital region, because of their similar clinical presentations, anatomical locations, radiological findings, and mistaken histopathological features. It is essential to distinguish myxoid chondrosarcoma from the chondroid variant of chordoma, because of the different treatment protocol and prognostic importance. We present such a location-based diagnostic dilemma, solved successfully with ancillary immunohistochemistry.

  20. Chondrosarcoma of the nasal septum

    International Nuclear Information System (INIS)

    Yamamoto, Seiji; Motoori, Ken; Ueda, Takuya; Osaka, Iwao; Takano, Hideyuki; Nagata, Hiroshi

    2002-01-01

    The nasal septum is a particularly rare site of origin of chondrosarcoma. Cranial base invasion may be at hand, with such lesions making complete tumor removal difficult. MRI techniques allow precise definition of tumor extent. In the described case, CT and Dynamic MR imaging were performed in a case of chondrosarcoma of the nasal septum. Imaging clearly illustrated size and extent of the mass with central regions of internal calcification. Dynamic MRI was additionally performed, which helped to define the presumed origin of the lesion from the nasal septum. (orig.)

  1. Clonal evolution through loss of chromosomes and subsequent polyploidization in chondrosarcoma.

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    Linda Olsson

    Full Text Available Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells may polyploidize. Sixteen chondrosarcomas were investigated by single nucleotide polymorphism (SNP array and the majority displayed SNP patterns indicative of a hyperhaploid-hypodiploid origin, with or without subsequent polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of heterozygosity was commonly found, resulting from chromosome loss and subsequent duplication of monosomic chromosomes giving rise to uniparental disomy. Additional gains, losses and rearrangements of genetic material, and even repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in highly complex karyotypes. Loss of chromosomes and subsequent polyploidization was not restricted to a particular chondrosarcoma subtype and, although commonly found in chondrosarcoma, binucleated cells did not seem to be involved in these events.

  2. Clonal evolution through loss of chromosomes and subsequent polyploidization in chondrosarcoma.

    Science.gov (United States)

    Olsson, Linda; Paulsson, Kajsa; Bovée, Judith V M G; Nord, Karolin H

    2011-01-01

    Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells may polyploidize. Sixteen chondrosarcomas were investigated by single nucleotide polymorphism (SNP) array and the majority displayed SNP patterns indicative of a hyperhaploid-hypodiploid origin, with or without subsequent polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of heterozygosity was commonly found, resulting from chromosome loss and subsequent duplication of monosomic chromosomes giving rise to uniparental disomy. Additional gains, losses and rearrangements of genetic material, and even repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in highly complex karyotypes. Loss of chromosomes and subsequent polyploidization was not restricted to a particular chondrosarcoma subtype and, although commonly found in chondrosarcoma, binucleated cells did not seem to be involved in these events.

  3. Dedifferentiated chondrosarcoma: use of MRI to guide needle biopsy

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    Saifuddin, A. E-mail: asaifuddin@aol.com; Mann, B.S.; Mahroof, S.; Pringle, J.A.S.; Briggs, T.W.R.; Cannon, S.R

    2004-03-01

    AIM: To describe the use of MRI to identify and biopsy areas of dedifferentiation in patients with a suspected diagnosis of dedifferentiated chondrosarcoma. MATERIALS AND METHODS: Low-grade chondrosarcoma is characterized at magnetic resonance imaging (MRI) as having a lobulate, hyperintense appearance on T2-weighted spin-echo sequences. T2-weighted MR images were assessed in 15 patients with a final pathological diagnosis of dedifferentiated chondrosarcoma for regions of atypical reduced signal intensity. Information regarding the site of ultrasound or computed tomography (CT)-guided biopsy was available in 10 cases. RESULTS: Nine patients were male and six female with a mean age of 60 years (range 25-77 years). The sites involved were the distal femur (n=4), pelvis (n=3), proximal femur (n=4), femoral diaphysis (n=1), proximal humerus (n=2) and proximal tibia (n=1). The dedifferentiated component consisted of osteosarcoma (n=5), malignant fibrous histiocytoma (n=6), spindle cell sarcoma (n=1), leiomyosarcoma (n=1) and pleomorphic sarcoma (n=1). In 14 of the 15 cases, areas of lower signal intensity lacking in lobulation were identified. In nine of the 10 cases, biopsy site included such areas and yielded high-grade sarcoma. CONCLUSIONS: Dedifferentiation within chondrosarcoma may be identified on T2-weighted MRI as areas of reduced signal intensity. These areas should be the preferred site of biopsy.

  4. Gadd45β expression in chondrosarcoma: A pilot study for diagnostic and biological implications in histological grading

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    Ishido Yasuhiro

    2010-10-01

    Full Text Available Abstract Background Although the diagnosis of chondrosarcoma, especially the distinction between enchondroma and low-grade chondrosarcoma or low-grade chondrosarcoma and high-grade chondrosarcoma, is pathologically difficult, differential diagnosis is very important because the treatment strategies for these diseases are completely different. The grading system is crucial in predicting biologic behavior and prognosis, however, exact pathological grading is difficult using only routine examinations because the criteria of the grading system are not necessarily definitive. Growth arrest and DNA damage-inducible protein 45β (GADD45β is an essential molecule for chondrocytes during terminal differentiation. In the present study, we investigated the immunohistochemical expression of GADD45β in enchondroma, and chondrosarcoma of histological grades I, II, and III, to clarify the diagnostic significance of GADD45β in pathological grading of chondrosarcoma. Methods Twenty samples (enchondroma = 6, chondrosarcoma grade I = 7, grade II = 6, grade III = 1 were used for immunohistochemical analysis to investigate the expression of GADD45β. Quantitative analysis was performed to compare the number of GADD45β positive cells and pathological grading. Results Over 70% of the cells in enchondromas expressed GADD45β. On the other hand, the expression of GADD45β decreased significantly according to the histological grade of chondrosarcoma (grade I: 45%; grade II: 13.8%; and grade III: 3.8%. Conclusions The association of GADD45β expression and pathological grading of chondrosarcoma in the present study suggests that the immunohistochemical study of GADD45β may be a specific diagnostic parameter for chondrosarcoma cell differentiation.

  5. A case of intracranial mesenchymal chondrosarcoma

    International Nuclear Information System (INIS)

    Hoshino, Masami; Tanji, Hiroyuki; Watanabe, Masakazu

    1981-01-01

    Intracranial mesenchymal chondrosarcoma is very rare, only 14 cases being reported in Europe and in the United States of America. Recently we experienced a case in which the follow-up indicating computed tomograms (CT) demonstrated interesting data on the radiosensitivity of this tumor. The patient, a 14-year-old female was admitted to our hospital with the complaint of left hemiplegia which had gradually progressed. CT revealed an area spreading upward from the right median base of the skull and consisted of two components showing (A) a density as high as that of calcium and (B) a density higher than that of surrounding brain tissue, but much lower than that of calcium. Temporoparietal craniotomy was performed to resect approximately one-half of the tumor. Histological finding revealed mesenchymal chondrosarcoma. The component-A was though to be a cartilaginous tissue, and-B to be an undifferentiated mesenchymal tissue. Postoperative irradiation of 7,000 rad was initiated. The effect of radiotherapy as seen on computed tomograms is as follows, (1) decrease in the volume of the tumor by 26%, (2) decrease in density and enhancement of the area which is considered to be the undifferentiated mesenchymal cells, (3) mild reduction of the area which is considered to be the caltilaginous tissue, and (4) a very high density of the entire tumor similar in degree to that of the bone one year later. These results suggested that radiotherapy is effective for this tumor. (author)

  6. Biological aspects of chondrosarcoma: Leaps and hurdles.

    Science.gov (United States)

    Mery, Benoîte; Espenel, Sophie; Guy, Jean-Baptiste; Rancoule, Chloé; Vallard, Alexis; Aloy, Marie-Thérèse; Rodriguez-Lafrasse, Claire; Magné, Nicolas

    2018-06-01

    Chondrosarcomas are characterized by their chemo- and radioresistance leading to a therapeutic surgical approach which remains the only available treatment with a 10-year survival between 30% and 80% depending on the grade. Non-surgical treatments are under investigation and rely on an accurate biological understanding of drug resistance mechanisms. Novel targeted therapy which represents a new relevant therapeutic approach will open new treatment options by targeting several pathways responsible for processes of proliferation and invasion. Survival pathways such as PI3K, AKT, mTOR and VEGF have been shown to be involved in proliferation of chondrosarcoma cells and antiapoptotic proteins may also play a relevant role. Other proteins such as p53 or COX2 have been identified as potential new targets. This review provides an insight into the biological substantial treatment challenges of CHS and focuses on improving our understanding of CH biology through an overview of major signaling pathways that could represent targets for new therapeutic approaches. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Chondrosarcoma: With Updates on Molecular Genetics

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    Mi-Jung Kim

    2011-01-01

    Full Text Available Chondrosarcoma (CHS is a malignant cartilage-forming tumor and usually occurs within the medullary canal of long bones and pelvic bones. Based on the morphologic feature alone, a correct diangosis of CHS may be difficult, Therefore, correlation of radiological and clinicopathological features is mandatory in the diagnosis of CHS. The prognosis of CHS is closely related to histologic grading, however, histologic grading may be subjective with high inter-observer variability. In this paper, we present histologic grading system and clinicopathological and radiological findings of conventional CHS. Subtypes of CHSs, such as dedifferentiated, mesenchymal, and clear cell CHSs are also presented. In addition, we introduce updated cytogenetic and molecular genetic findings to expand our understanding of CHS biology. New markers of cell differentiation, proliferation, and cell signaling might offer important therapeutic and prognostic information in near future.

  8. [Dedifferentiated chondrosarcoma: radiologic-pathologic correlation].

    Science.gov (United States)

    Bierry, G; Feydy, A; Larousserie, F; Pluot, E; Guerini, H; Campagna, R; Dufau-Andreu, C; Anract, P; Babinet, A; Dietemann, J L; Chevrot, A; Drapé, J L

    2010-03-01

    Dedifferentiated chondrosarcomas are highly malignant tumors characterized by conventional low-grade chondrosarcoma with abrupt transition to foci that have dedifferentiated into a higher-grade noncartilaginous more aggressive sarcoma. The dedifferentiated component, an osteosarcoma or fibrosarcoma, determines the prognosis. Its identification is key for management. A diagnosis of dedifferentiated chondrosarcoma should be suggested by the presence of "tumoral dimorphism" with cartilaginous component and aggressive lytic component invading adjacent soft tissues.

  9. TCF-1 participates in the occurrence of dedifferentiated chondrosarcoma.

    Science.gov (United States)

    Xu, Xiaolong; Tang, Xiaodong; Guo, Wei; Yang, Kang; Ren, Tingting

    2016-10-01

    The present study demonstrated that T cell factor 1 (TCF-1) protein, a component of the canonical Wnt/β-catenin signaling pathway, can regulate the expression of runt-related transcription factor 2 (runx2) gene and Sry-related HMG box 9 (sox9) gene, which may participate in the differentiation of chondrosarcoma. Dedifferentiated chondrosarcoma (DDCS) is a special variant of conventional chondrosarcoma (CCS), associated with poor survival and high metastasis rate. However, little is known about the mechanism of its occurrence; thus, no effective treatment is available except surgery. Earlier, high expression of runx2 and low expression of sox9 were found in DDCS compared with CCS. Using Western blot to detect clinical tissue samples (including 8 CCS samples and 8 DDCS samples) and immunohistochemistry to detect 85 different-grade chondrosarcoma specimens, a high expression of TCF-1 in DDCS tissues was found compared with CCS tissues. This difference in expression was related to patients' prognosis. Results of luciferase, chromatin immunoprecipitation, and gel electrophoresis mobility shift assays demonstrated that TCF-1 protein could bind to the promoter of runx2 gene directly and sox9 gene indirectly. Hence, it could regulate expression of runx2 gene positively and sox9 gene negatively. Furthermore, in vitro and in vivo experiments showed that TCF-1 protein was closely related to the phenotype and aggressiveness of chondrosarcoma. In conclusion, this study proved that TCF-1 participates in the dedifferentiation of DDCS, which may be mediated by runx2 gene and sox9 gene. Also, TCF-1 can be of important prognostic value and a promising therapeutic target for DDCS patients.

  10. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    International Nuclear Information System (INIS)

    Hamm, Christopher A; Wang, Deli; Malchenko, Sergey; Fatima Bonaldo, Maria de; Casavant, Thomas L; Hendrix, Mary JC; Soares, Marcelo B; Stevens, Jeff W; Xie, Hehuang; Vanin, Elio F; Morcuende, Jose A; Abdulkawy, Hakeem; Seftor, Elisabeth A; Sredni, Simone T; Bischof, Jared M

    2010-01-01

    Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis

  11. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    Directory of Open Access Journals (Sweden)

    Hamm Christopher A

    2010-09-01

    Full Text Available Abstract Background Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. Methods To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. Results The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. Conclusion This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that

  12. Radiation-induced cerebellar chondrosarcoma. Case report

    International Nuclear Information System (INIS)

    Bernstein, M.; Perrin, R.G.; Platts, M.E.; Simpson, W.J.

    1984-01-01

    The authors report a case of chondrosarcoma arising in the cerebellum 16 years after treatment of a cerebellar malignant astrocytoma by subtotal resection and irradiation. It is thought that the chondrosarcoma arising within the intracranial cavity was a probable consequence of previous ionizing radiation

  13. The expression of miR-181a-5p and miR-371b-5p in chondrosarcoma.

    Science.gov (United States)

    Mutlu, S; Mutlu, H; Kirkbes, S; Eroglu, S; Kabukcuoglu, Y S; Kabukcuoglu, F; Duymus, T M; ISık, M; Ulasli, M

    2015-07-01

    Chondrosarcomas are malignant tumors of chondrocytes that affect bones and joints, and it represents the third most common type of primary bone tumors. Chondrosarcoma is difficult to treat because it is relatively resistant to both chemotherapy and radiation. Thus, surgery remains the best available treatment. It is important to find new diagnostic markers and improve treatment options. miRNAs are small non-coding transcripts (19-25 nucleotides) that regulate gene expression via targeting complementary sequences within messenger RNAs (mRNAs). miRNAs have been shown to be involved in regulation of many biochemical pathways. Dysregulated expression of many miRNAs has also been associated with multiple human diseases, such as cancer. 18 surgical chondrosarcoma specimens were obtained from patients. RNA extractions were performed from decalcified paraffin embedded tissues. The aim of this study was to investigate the expression levels of miR-181a and miR-371b in patients with chondrosarcoma by using RT-PCR and to evaluate the relationship between these miRNAs and chondrosarcoma. miR-181a was found to be upregulated in chondrosarcoma specimens whereas no significant alteration was found for miR-371b expression. It has been proposed that miRNA expression studies might be used as diagnostic, prognostic marker in cancer. miRNA expression data produced in our study may contribute future chondrosarcoma diagnosis and therapy.

  14. Reappraisal of mesenchymal chondrosarcoma: novel morphologic observations of the hyaline cartilage and endochondral ossification and beta-catenin, Sox9, and osteocalcin immunostaining of 22 cases.

    Science.gov (United States)

    Fanburg-Smith, Julie C; Auerbach, Aaron; Marwaha, Jayson S; Wang, Zengfeng; Rushing, Elisabeth J

    2010-05-01

    Mesenchymal chondrosarcoma, a rare malignant round cell and hyaline cartilage tumor, is most commonly intraosseous but can occur in extraskeletal sites. We intensively observed the morphology and applied Sox9 (master regulator of chondrogenesis), beta-catenin (involved in bone formation, thought to inhibit chondrogenesis in a Sox9-dependent manner), and osteocalcin (a marker for osteoblastic phenotype) to 22 central nervous system and musculoskeletal mesenchymal chondrosarcoma. Cases of mesenchymal chondrosarcoma were retrieved and reviewed from our files. Immunohistochemistry and follow-up were obtained on mesenchymal chondrosarcoma and tumor controls. Twenty-two mesenchymal chondrosarcomas included 5 central nervous system (all female; mean age, 30.2; mean size, 7.8 cm; in frontal lobe [n = 4] and spinal cord [n = 1]) and 17 musculoskeletal (female-male ratio, 11:6; mean age, 31.1; mean size, 6.2 cm; 3 each of humerus and vertebrae; 2 each of pelvis, rib, tibia, neck soft tissue; one each of femur, unspecified bone, and elbow soft tissue). The hyaline cartilage in most tumors revealed a consistent linear progression of chondrocyte morphology, from resting to proliferating to hypertrophic chondrocytes. Sixty-seven percent of cases demonstrated cell death and acquired osteoblastic phenotype, cells positive for osteocalcin at the site of endochondral ossification. Small round cells of mesenchymal chondrosarcoma were negative for osteocalcin. SOX9 was positive in both components of 21 of 22 cases of mesenchymal chondrosarcoma. beta-Catenin highlighted rare nuclei at the interface between round cells and hyaline cartilage in 35% cases. Control skull and central nervous system cases were compared, including chondrosarcomas and small cell osteosarcoma, the latter positive for osteocalcin in small cells. Mesenchymal chondrosarcoma demonstrates centrally located hyaline cartilage with a linear progression of chondrocytes from resting to proliferative to hypertrophic

  15. Naso-sinus chondrosarcoma: a case report

    International Nuclear Information System (INIS)

    Kim, Yeo Ju; Ahn, Kook Jin; Lee, Youn Soo; Paik, Moon Hee; Kim, Jee Young; Hahn, Seong Tai

    2007-01-01

    Chondrosarcomas are malignant tumors of the cartilage that rarely involve the sinonasal region. Here, we describe a case of histologically verified naso-sinus chondrosarcoma in a 40-year-old female presenting with nasal stuffiness and anosmia. The tumor presented on computed tomography (CT) as an expanding soft tissue mass with bone destruction and pressure erosion. The magnetic resonance images (MRI) of the tumor demonstrated high signals on T2-weighted images with nodular and papillary enhancement along the periphery on T1-weighted images with contrast enhancement. The presence of these typical imaging features should be very helpful in diagnosing chondrosarcoma involving the sinonasal region

  16. Naso-sinus chondrosarcoma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yeo Ju; Ahn, Kook Jin; Lee, Youn Soo; Paik, Moon Hee; Kim, Jee Young; Hahn, Seong Tai [Mary' s Hospital, The Catholic University of Korea, Seoul (Korea, Republic of)

    2007-03-15

    Chondrosarcomas are malignant tumors of the cartilage that rarely involve the sinonasal region. Here, we describe a case of histologically verified naso-sinus chondrosarcoma in a 40-year-old female presenting with nasal stuffiness and anosmia. The tumor presented on computed tomography (CT) as an expanding soft tissue mass with bone destruction and pressure erosion. The magnetic resonance images (MRI) of the tumor demonstrated high signals on T2-weighted images with nodular and papillary enhancement along the periphery on T1-weighted images with contrast enhancement. The presence of these typical imaging features should be very helpful in diagnosing chondrosarcoma involving the sinonasal region.

  17. Clinical Benefit of Pazopanib in a Patient with Metastatic Chondrosarcoma: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Onoufrios Tsavaris

    2018-03-01

    Full Text Available Chondrosarcoma is a rare malignancy characterized by the production of cartilage matrix, displaying heterogeneous histopathology and clinical behavior. Due to lack of effective treatment for advanced disease, the clinical management of metastatic chondrosarcoma is exceptionally challenging. Chondrosarcomas harbor molecular abnormalities, such as overexpression of platelet-derived growth factor receptor (PDGFR-alpha and PDGFR-beta, which are required for cancer development, progression, and metastasis. Pazopanib is a potent and selective multitargeted tyrosine kinase inhibitor, which co-inhibits stem cell growth factor receptor (c-KIT, fibroblast growth factor receptor (FGFR, PDGFR, and vascular endothelial growth factor receptor (VEGFR and has demonstrated clinical activity in patients with advanced previously treated soft tissue sarcoma. Herein, we describe the unique case of a patient with metastatic chondrosarcoma who derived clinical benefit from pazopanib after first-line chemotherapy failure.

  18. Mesenchymal chondrosarcoma--a case report.

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    Tyagi S

    1992-01-01

    Full Text Available A Case of extraosseous mesenchymal chondrosarcoma occurring in the occipital region in a 26 year old male is being reported. The patient remained free from recurrence on any metastasis even after 2 years of the tumor resection.

  19. Primary mesenchymal chondrosarcoma of the kidney with synchronous implant and infiltrating urothelial carcinoma of the ureter

    Directory of Open Access Journals (Sweden)

    Xu Hua

    2012-09-01

    Full Text Available Abstract Primary mesenchymal chondrosarcoma of the kidney is rare, and it shows distinct undifferentiated tumor cells and well differentiated cartilagenous components. Also assident infiltrating urothelial carcinoma of the ureter is an extremely rare cancer. We report a case of primary mesenchymal chondrosarcoma occurring in the left kidney with an ipsilateral and distinct distal ureteric implant, and a coexisting infiltrating urothelial carcinoma of the ureter in a 64-year-old man. Histopathological examination and immunohistochemical studuies showed the classic features of mesenchymal chondrosarcoma in kidney, as well as a few infiltrating urothelial in ureter. Multitarget fluorescence in situ hybridization (FISH suggested that the development of the urothelial carcinoma in the ureter may be triggered or induced by the chondrosarcoma component. The patient died 2 month after left nephro-ureterectomy. This is the first reported case of a primary mesenchymal chondrosarcoma of the kidney with coexisting infiltrating urothelial carcinoma of the ureter. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1522835667751019

  20. Nasal Osteogenic Chondrosarcoma: A Case Report | Adeniji | West ...

    African Journals Online (AJOL)

    At emergency tracheostomy, examination under anaesthesia, meticulous nasal and nasopharyngeal tumour clearance was done. Histopathological examination of the mass revealed osteogenic chondrosarcoma. CONCLUSION: Though rare, osteogenic chondrosarcoma affects nasal bones. Clinically the tumour mimicks ...

  1. HDAC inhibitor-loaded bone cement for advanced local treatment of osteosarcoma and chondrosarcoma.

    Science.gov (United States)

    Tonak, Marcus; Becker, Marc; Graf, Claudine; Eckhard, Lukas; Theobald, Matthias; Rommens, Pol-Maria; Wehler, Thomas C; Proschek, Dirk

    2014-11-01

    The treatment of osteosarcoma, especially wide resection, is challenging. An additional local drug therapy after resection using anti-neoplastic bone cement (Polymethylmethacrylate (PMMA)) could help improve the outcome of therapy. In this study, we evaluated the effects of PMMA loaded with valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) on the cell activity of a SaOs-2 cell culture, as well as the elution rate of the drugs out of the bone cement. In our experiments, we used the SaOs-2 osteosarcoma and the SW1353 chondrosarcoma cell line. Bone cement clots (5 g) were prepared and loaded with different drug concentrations of VPA (25 mg and 50 mg) and SAHA (1 mg, 2.5 mg and 5 mg). Two control groups were established, one with a native cement clot, the other with human mesenchymal stem cells, in order to evaluate toxicity on non tumor-cells. Cell activity was measured using an Alamar Blue assay on days 1, 2, 3, 4 and 7. The cement clots were additionally examined in a material testing unit for biomechanical and structural changes. Tumor cells showed a significant and complete reduction of activity under therapy with VPA and SAHA. Drug release of VPA was extensive between days 0 and 3 and decreased progressively to day 7. Cumulative drug concentration in the medium continuously increased. Biomechanical testing of the cement clots showed no differences in stability and architecture compared to the control group. SaOs-2 and SW1353 cells with medium from native cement clots without drug therapy presented a cell activity of 100% in all groups and during all measurements. Human mesenchymal stem cells were not significantly affected during therapy with VPA and low concentrations of SAHA. In contrast, cell activity of human mesenchymal stem cells was significantly reduced under therapy with higher concentrations of SAHA, with an approximately linear decrease between days 0-3 and a rapidly decreasing activity between days 4-7. A local cytotoxic therapy in the

  2. Tumor grade-related thallium-201 uptake in chondrosarcomas

    International Nuclear Information System (INIS)

    Kaya, G.C.; Demir, Y.; Ozkal, S.

    2010-01-01

    Diagnosis of low-grade chondrosarcoma, especially discrimination between enchondroma and low-grade chondrosarcoma, may be difficult pathologically. The aim of this study was to evaluate the value of thallium-201 (Tl-201) scintigraphy in the diagnosis of chondrosarcoma and to investigate whether there was a correlation between Tl-201 uptake and tumor grade. We retrospectively evaluated 121 patients with pathologically proven bone and soft tissue tumors diagnosed between the years 1999 and 2007. All patients were followed by the Bone and Soft Tissue Tumor Working Group in our hospital. Twenty-three patients, mean age 44±15 (range 17-72) years, with a diagnosis of cartilaginous tumors were included. Increased Tl-201 uptake at the lesion sites greater than background was evaluated as malignant tumor. For the pathologic classification, a grading system (grade 1-3) based on the histopathologic findings was used. Pearson correlation coefficient was used to determine whether there was any correlation between Tl-201 uptake and tumor grade in chondrosarcoma. There were 7 enchondromas and 16 chondrosarcomas. Four of 16 patients with chondrosarcoma had lesions pathologically classified as grade 3, 5 as grade 2, and 7 had grade 1 chondrosarcoma. Increased Tl-201 uptake was observed in all patients with grade 3 chondrosarcoma and 2 patients with grade 2 chondrosarcoma. Of 10 patients with chondrosarcoma, 3 grade 2 chondrosarcomas and 7 grade 1 chondrosarcomas, there was no Tl-201 uptake in the tumor region. A significant correlation was found between Tl-201 uptake and tumor grade in chondrosarcoma (p=0.002, r=0.71). Only a few reports in literature have demonstrated false negative results in low-grade chondrosarcoma. Tl-201 uptake was related to tumor grade in chondrosarcoma. If there is a possibility of chondrosarcoma, Tl-201 scintigraphy should be reported with caution. (author)

  3. The Human Cell Atlas.

    Science.gov (United States)

    Regev, Aviv; Teichmann, Sarah A; Lander, Eric S; Amit, Ido; Benoist, Christophe; Birney, Ewan; Bodenmiller, Bernd; Campbell, Peter; Carninci, Piero; Clatworthy, Menna; Clevers, Hans; Deplancke, Bart; Dunham, Ian; Eberwine, James; Eils, Roland; Enard, Wolfgang; Farmer, Andrew; Fugger, Lars; Göttgens, Berthold; Hacohen, Nir; Haniffa, Muzlifah; Hemberg, Martin; Kim, Seung; Klenerman, Paul; Kriegstein, Arnold; Lein, Ed; Linnarsson, Sten; Lundberg, Emma; Lundeberg, Joakim; Majumder, Partha; Marioni, John C; Merad, Miriam; Mhlanga, Musa; Nawijn, Martijn; Netea, Mihai; Nolan, Garry; Pe'er, Dana; Phillipakis, Anthony; Ponting, Chris P; Quake, Stephen; Reik, Wolf; Rozenblatt-Rosen, Orit; Sanes, Joshua; Satija, Rahul; Schumacher, Ton N; Shalek, Alex; Shapiro, Ehud; Sharma, Padmanee; Shin, Jay W; Stegle, Oliver; Stratton, Michael; Stubbington, Michael J T; Theis, Fabian J; Uhlen, Matthias; van Oudenaarden, Alexander; Wagner, Allon; Watt, Fiona; Weissman, Jonathan; Wold, Barbara; Xavier, Ramnik; Yosef, Nir

    2017-12-05

    The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

  4. Chondrosarcoma of the patella: A case report.

    Science.gov (United States)

    Ye, Conglin; Luo, Zhiping; Zeng, Jin; Dai, Min

    2017-09-01

    Chondrosarcoma, characterized by the production of cartilage matrix, is a common bone tumor, accounting for 20% to 27% of all malignant bone tumors. It often occurs in the cartilage of the pelvis, femur, tibia, and humerus. However, chondrosarcoma of the patella is extremely rare. The present study describes a case of chondrosarcoma affecting the right patella in a 68-year-old woman. The chief complaints were painful swelling and limitation of motion of the right knee for about half a year. The pain was a kind of dull ache. The skin around the right knee was red and hot. Moreover, she had a claudication gait due to the symptoms. Irregular lytic lesions with ill-defined margins in the patella were determined through computed tomography and magnetic resonance imaging. The diagnosis of primary grade II chondrosarcoma was finally confirmed on the basis of postoperative pathological examination. The patient underwent an open surgery named extensive resection of patellar tumor to remove the tumor tissue completely. The patient was discharged without any complications 1 week after the surgery. At the 3-month follow-up, the patient was completely free from pain during daily activities, and normal range of motion of the right knee was achieved. Her gait was normal. There was no evidence of recurrence. We believe that an extensive resection is suitable for treating chondrosarcoma to avoid as far as possible local recurrence. An awareness of the potential for chondrosarcoma to present in the patella is crucial for both orthopedic surgeons and radiologists when confronted with similar cases. Besides, as reports of chondrosarcoma of the patella are rare, this study adds a better understanding of this rare condition to the medical literature.

  5. The human cell atlas

    DEFF Research Database (Denmark)

    Regev, Aviv; Teichmann, Sarah A.; Lander, Eric S.

    2017-01-01

    The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international...... collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells...... in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early...

  6. An orthotopic mouse model for chondrosarcoma of bone provides an in vivo tool for drug testing

    NARCIS (Netherlands)

    van Oosterwijk, Jolieke G.; Plass, Jacqueline Regina Maria; Meijer, Danielle; Que, Ivo; Karperien, Hermanus Bernardus Johannes; Bovée, Judith V.M.G.

    2015-01-01

    Chondrosarcoma is a malignant cartilaginous tumor of the bone. Recently, mutations in isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) were identified in central chondrosarcomas. As chondrosarcomas are notoriously resistant to conventional treatment modalities, the need for

  7. Molecular oncogenesis of chondrosarcoma: impact for targeted treatment.

    Science.gov (United States)

    Speetjens, Frank M; de Jong, Yvonne; Gelderblom, Hans; Bovée, Judith V M G

    2016-07-01

    The prognosis of patients with unresectable or metastatic chondrosarcoma of the bone is poor. Chondrosarcomas are in general resistant to chemotherapy and radiotherapy. This review discusses recent developments in the characterization of molecular pathways involved in the oncogenesis of chondrosarcoma that should be explored to improve prognosis of patients with advanced chondrosarcoma. The different oncogenic pathways for chondrosarcoma have become better defined. These include alterations in pathways such as isocitrate dehydrogenase mutation, hedgehog signalling, the retinoblastoma protein and p53 pathways, apoptosis and survival mechanisms, and several tyrosine kinases. These specific alterations can be employed for use in clinical interventions in advanced chondrosarcoma. As many different genetic alterations in chondrosarcoma have been identified, it is of the utmost importance to classify druggable targets that may improve the prognosis of chondrosarcoma patients. In recent years an increased number of trials evaluating targeted therapies are being conducted. As chondrosarcoma is an orphan disease consequently all studies are performed with small numbers of patients. The results of clinical studies so far have been largely disappointing. Therapeutic intervention studies of these new targets emerging from preclinical studies are of highest importance to improve prognosis of chondrosarcoma patients with advanced disease.

  8. Chondrosarcoma : MR imaging findings correlated with pathologic classification and grade

    International Nuclear Information System (INIS)

    Cho, Seong Whi; Kang, Heung Sik; Kim, Sam Soo; Lee, Sang Hyun; Cho, Jeong Yeon; Yeon, Kyung Mo

    1996-01-01

    To evaluate the MR imaging findings of chondrosarcomas by correlation with pathologic classification and grade. We performed MR imaging-pathologic correlation of nineteen chondrosarcomas. Conventional chondrosarcomas accounted for 15 cases (grade I:6, II:6, III:3) and the mesenchymal and dedifferentiated types each accounted for two. MR signal intensity (SI) of the tumor on T1- and T2-weighted images (T1WI and T2WI, respectively), was classified as homogeneous or heterogeneous low-, iso- or high SI, and enhancing pattern as marginal, marginal and septal, marginal and nodular, or diffuse enhancement. Eighteen cases of chondrosarcomas (95%) showed homogeneous or heterogeneous low- or iso SI on T1WI and high SI on T2WI. Low grade conventional chondrosarcomas showed marginal and septal (n=8/10) or marginal (n=2/10) enhancement on Gd-enhanced MR images. Grade III conventional chondrosarcomas showed marginal or marginal and nodular enhancement. Dedifferentiated and mesenchymal chondrosarcomas showed marginal and nodular or diffuse enhancement. Chondrosarcomas showed iso- or low SI on T1WI and high SI on T2WI. Marginal and septal enhancement was demonstrated on Gd-enhanced MR images of grade I and II conventional chondrosarcomas. If a tumor showed a marginal and nodular or diffuse enhancing pattern, this suggested it was a of high grade chondrosarcoma

  9. Doxycycline and its quaternary ammonium derivative for adjuvant therapies of chondrosarcoma.

    Science.gov (United States)

    Miladi, Imen; Vivier, Magali; Dauplat, Marie-Mélanie; Chatard, Morgane; Besse, Sophie; Vidal, Aurélien; Chassain, Karine; Jean, Betty; Forestier, Christiane; Chezal, Jean-Michel; Rédini, Francoise; Degoul, Francoise; Miot-Noirault, Elisabeth

    2017-09-01

    This study was conducted during the development of innovative treatment targeting the microenvironment of chondrosarcoma. In this context, MMP inhibitors were conjugated with a quaternary ammonium (QA) function as a targeting ligand to proteoglycans of chondrosarcoma extracellular matrix. Here we report the proof of concept of this strategy applied to the MMP13 inhibitor, doxycycline (Dox). A quaternary ammonium derivative of the MMP13 inhibitor doxycycline (QA-Dox) was synthesized, and its anticancer activity was evaluated in the Swarm rat chondrosarcoma (SRC) model compared with the parent drug doxycycline, in vitro and in vivo. In vivo, dox and QA-Dox efficiency was assessed at equimolar doses according to a q4dx4 schedule by monitoring tumour volume by MRI and PG-targeted scintigraphy. Molecular mechanism (MMP13 expression, proteoglycan level) and histology studies were performed on tumours. The link of QA targeting function to Dox maintained the MMP13 inhibitory activity in vitro. Interestingly, the bacteriostatic activity was lost. SRC cells incubated with both drugs were blocked in S and G2 M phases. Tumour growth inhibition (confirmed by histology) was observed for both Dox and QA-Dox. Undesirable blood effects (leukocyte decrease) were reduced when Dox was targeted to tumour tissue using the QA function. In the SRC model, the MMP13 inhibitor Dox and its QA derivative are promising as adjuvant therapies for chondrosarcoma management.

  10. CHONDROSARCOMA OF BONE - ONCOLOGIC AND FUNCTIONAL RESULTS

    NARCIS (Netherlands)

    VANLOON, CJM; VETH, RPH; PRUSZCZYNSKI, M; WOBBES, T; LEMMENS, JAM; VANHORN, J

    1994-01-01

    A retrospective review of 27 patients (21 males and 6 females) with chondrosarcoma of bone was performed to evaluate the oncologic and functional results. The average age of the patients was 48 years (range: 17-76). The tumor sites were pelvis in 10 cases, distal femur in 2, proximal tibia in 3, rib

  11. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  12. Case report 460: Synovial chondrosarcoma of left knee

    International Nuclear Information System (INIS)

    Manivel, J.C.; Dehner, L.P.; Thompson, R.

    1988-01-01

    The case is presented of a 50-year-old man who presented with a mass around the left knee which radiologically was calcified heavily and eroded bone. A final diagnosis over a period of time of synovial chondrosarcoma was established. A description in depth of the types of synovial chondromatosis and the possible etiology of synovial chondrosarcoma was included in the manuscript. The diagnostic (radiological and pathological) features of the entity were described and the rarity of synovial chondrosarcoma was emphasized. (orig.)

  13. Costal chondrosarcoma requiring differential diagnosis from metastatic tumor.

    Science.gov (United States)

    Matsuoka, Katsunari; Ueda, Mitsuhiro; Miyamoto, Yoshihiro

    2017-02-01

    Although chondrosarcoma is a common malignant bone tumor, cases arising in the rib are relatively rare. We experienced a case of chondrosarcoma arising in the right 10th rib during follow-up after lung cancer surgery. Although the finding of an osteolytic mass suggested a metastatic bone tumor, 18F-fluorodeoxyglucose positron-emission tomography demonstrated low fluorodeoxyglucose uptake, and a primary bone tumor was suspected. The bone tumor was resected and diagnosed as chondrosarcoma. Four years after resection, there has been no recurrence or metastasis. Positron-emission tomography was useful for differential diagnosis between a chondrosarcoma and a metastatic bone tumor.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-15

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

  16. Celastrol inhibits chondrosarcoma proliferation, migration and invasion through suppression CIP2A/c-MYC signaling pathway

    Directory of Open Access Journals (Sweden)

    Jinhui Wu

    2017-05-01

    Full Text Available Chondrosarcomas (CS is the second most frequent tumors of cartilage origin. A small compound extracted from Thunder God Vine (Tripterygium wilfordii Hook. F. called celastrol can directly bound CIP2A protein and effectively inhibit cell proliferation and induce apoptosis in several cancer cells. However, little knowledge is concern about the important role of CIP2A in CS patients and the therapeutic value of celastrol on CS. Our results showed that CIP2A and c-MYC were verified to be oncoproteins by detecting their mRNA and protein expression in 10 human CS tissues by qRT-PCR and Western blots. After treatment of celastrol, the proliferation, migration and invasion were significantly inhibited; whereas the apoptosis was largely induced in human CS cell lines. In addition, celastrol inhibited the expression of CIP2A, c-MYC, and suppressed apoptotic proteins BAX and caspase-8 in human CS cells, on the other hand, it induced the expression of antiapoptotic protein Bcl-2. Finally, knockdown of CIP2A also inhibited the migration and invasion and induced apoptosis of human CS cells. To sum up, we found that celastrol had effects on inhibiting proliferation, migration, invasion and inducing apoptosis through suppression CIP2A/c-MYC signaling pathway in vitro, which may provide a new therapeutic regimen for CS.

  17. Chondrosarcoma of the larynx: treatment with radiotherapy

    International Nuclear Information System (INIS)

    Dailiana, T.; Thanos, L.; Papathanasiou, M.; Alexopoulou, E.; Papaioannou, G.; Kelekis, D.A.; Nomikos, P.; Kapranos, N.

    2002-01-01

    The case of a 50-year-old man with chondrosarcoma of the larynx treated with radiotherapy is reported. The patient presented with hoarseness and dyspnea. He underwent computed tomography (CT), which demonstrated a soft tissue mass of the larynx. Direct laryngoscopy with biopsy established the diagnosis of chondrosarcoma. Although experience with radiotherapy in these cases has been lacking in the literature, it was considered and eventually used, as radical surgery would result in severe cosmetic and functional impairment. Radiation therapy alone resulted in long-term remission of the tumour for more than 3 years. The patient has been followed up using CT and direct laryngoscopy for early detection of recurrence or metastases. (orig.)

  18. Curious case of extraskeletal myxoid chondrosarcoma

    Directory of Open Access Journals (Sweden)

    Sushilkumar Satish Gupta

    2017-01-01

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

  19. Human innate lymphoid cells.

    Science.gov (United States)

    Mjösberg, Jenny; Spits, Hergen

    2016-11-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-γ-mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  20. Glandular differentiation in dedifferentiated chondrosarcoma: molecular evidence of a rare phenomenon.

    Science.gov (United States)

    Jour, George; Liu, Yajuan; Ricciotti, Robert; Pritchard, Colin; Hoch, Benjamin L

    2015-09-01

    Epithelial glandular differentiation in dedifferentiated chondrosarcoma has not been described. Our patient was a 64-year-old man with a history of prostate cancer status post-radiation and hormonal therapy. On screening bone scan, he was found to have increased uptake in his right femoral shaft. Biopsy revealed intermediate-grade conventional chondrosarcoma. Subsequent femoral resection was remarkable for an intermediate-grade chondrosarcomatous component juxtaposed to an area composed of anastomosing nests and cords of malignant epithelial cells showing nuclear atypia and increased mitotic activity. A fibroblastic-appearing spindle cell population was intimately associated with the epithelial cells. The epithelial cells labeled with 34bE12, AE1/AE3, EMA, and Vimentin (both spindled and epithelial components) while being negative for prostate-specific antigen, prostate specific acid phosphatase, cytokeratin 20, thyroid transcription factor-1, and CDX2. The patient developed local recurrence 9 months after the initial resection but has had no metastatic disease and consistently undetectable prostate-specific antigen levels. Deep parallel sequencing of the dedifferentiated component showed a nonsynonymous mutation at exon 4 of IDH1 gene at codon R132 leading to a substitution of arginine, with serine confirming glandular differentiation in dedifferentiated chondrosarcoma. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Chondrosarcoma of the temporal bone: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Man Soo; Lee, Sang Youl; Chung, Jae Gul; Lee, Deok Hee; Jung, Seung Mun; Ryu, Dae Sik [Kang Nung Hospital, Ulsan Univ. Kangnung (Korea, Republic of)

    2001-07-01

    Chondrosarcoma of the temporal bone is a rare lesion. Clinically it has been confused with chordoma, glomus jugulare tumor and meningioma, among other conditions, and due to its anatomic location, cranial nerve palsy is frequently observed. We report a case involving a 50-year-old woman with chondrosarcoma of the temporal bone.

  2. Dedifferentiated chondrosarcoma in childhood: report of a case

    International Nuclear Information System (INIS)

    Herman, T.E.; McAlister, W.H.; Dehner, L.P.; Kaufman, B.A.

    1995-01-01

    Dedifferentiated chondrosarcoma is an unconventional chondrosarcoma of distinctive pathology. The tumor, not previously reported in childhood, is characterized by a very poor prognosis with an average survival of only 6 months. Imaging features include a lytic lesion, focal calcifications, and a soft tissue mass. (orig.)

  3. Synovial Chondrosarcoma in the Hand and Wrist: A Case Report

    International Nuclear Information System (INIS)

    An, Yeong Yi; Kim, Jee Young; Kang, Seok Jin; Kang, Yong Koo; Baik, Jun Hyun

    2010-01-01

    Synovial chondrosarcoma is extremely rare and arises de novo or from malignant transformation of synovial chondromatosis. It commonly involves large joints, such as the knee or hip. Here, we present an unusual case of synovial chondrosarcoma from synovial chondromatosis in the hand and wrist, clearly demonstrating the characteristic findings on plain radiograph and MR imaging

  4. Chondrosarcoma models : understanding chemoresistance mechanisms for use in targeted treatment

    NARCIS (Netherlands)

    Oosterwijk, Jolieke Gerdy van

    2013-01-01

    Primary bone tumors are rare, constituting 0.2% of all reported neoplasms. Malignant cartilage tumors of bone are classified as chondrosarcomas. Recurrent and metastatic disease as well as chondrosarcomas located at unresectable sites present a major problem, as conventional chemo- and radiotherapy

  5. Chondrosarcoma of the temporal bone: a case report

    International Nuclear Information System (INIS)

    Park, Man Soo; Lee, Sang Youl; Chung, Jae Gul; Lee, Deok Hee; Jung, Seung Mun; Ryu, Dae Sik

    2001-01-01

    Chondrosarcoma of the temporal bone is a rare lesion. Clinically it has been confused with chordoma, glomus jugulare tumor and meningioma, among other conditions, and due to its anatomic location, cranial nerve palsy is frequently observed. We report a case involving a 50-year-old woman with chondrosarcoma of the temporal bone

  6. Synovial Chondrosarcoma in the Hand and Wrist: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    An, Yeong Yi; Kim, Jee Young; Kang, Seok Jin; Kang, Yong Koo; Baik, Jun Hyun [Catholic University St. Vincent' s Hospital, Suwon (Korea, Republic of)

    2010-01-15

    Synovial chondrosarcoma is extremely rare and arises de novo or from malignant transformation of synovial chondromatosis. It commonly involves large joints, such as the knee or hip. Here, we present an unusual case of synovial chondrosarcoma from synovial chondromatosis in the hand and wrist, clearly demonstrating the characteristic findings on plain radiograph and MR imaging.

  7. Maffucci's syndrome associated with chondrosarcoma and aneurysm: case report

    International Nuclear Information System (INIS)

    Lim, Hyoung Gun; Yoo, Won Jong; Lim, Yeon Soo; Sung, Mi Sook; Chung Myung Hee; Lee, Hae Giu; Jung, So Lyung; Kim, Jea NA

    2002-01-01

    Maffucci syndrome is a rare congenital non-inherited condition characterized by multiple enchondromas and cutaneous hemangiomas. It is associated with increased risk of malignancy, including chondrosarcomas, and because of generalized mesodermal dysplasia, aneurysms can develop. We present a case of Maffucci syndrome associated with intracranial chondrosarcoma and aneurysm

  8. Maffucci's syndrome associated with chondrosarcoma and aneurysm: case report

    International Nuclear Information System (INIS)

    Lim, Hyoung Gun; Yoo, Won Jong; Lim, Yeon Soo; Sung, Mi Sook; Chung, Myung Hee; Lee, Hae Giu; Jung, So Lyung; Kim, Jae Na

    2002-01-01

    Maffucci syndrome is rare congenital non-inherited condition characterized by multiple enchondromas and cutaneous hemangiomas. It is associated with increased risk of malignancy, including chondrosarcomas, and because of generalized mesodermal dysplasia, aneurysms can develop. We present a case of maffucci syndrome associated with intracranial chondrosarcoma and aneurysm

  9. Renal Extra Skeletal Mesenchymal Chondrosarcoma: A Case Report.

    Science.gov (United States)

    Salehipour, Mehdi; Hosseinzadeh, Masood; Sisakhti, Afshin Molaei; Parvin, Vahid Abdol Mohammadi; Sadraei, Amin; Adib, Ali

    2017-05-01

    Primary mesenchymal chondrosarcoma of the Kidney is an extremely rare entity and very few cases have been reported in literature. We report a 22-year-old male with a right renal mass; after radical nephrectomy, pathologic examination revealed primary extra skeletal mesenchymal chondrosarcoma.

  10. Hyoid bone chondrosarcoma with cervical nodal metastasis: A case ...

    African Journals Online (AJOL)

    Background: Hyoid bone chondrosarcoma is a very rare condition. This study presents a case report of low-grade chondrosarcoma of hyoid bone with cervical nodal metastasis. The study also presents preoperative radiological investigations, pathological examination and the follow-up of the case. Case presentation: A 42 ...

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-07-14

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

  13. Human leukaemic cells

    International Nuclear Information System (INIS)

    Andronikashvili, E.L.; Mosulishvili, L.M.; Belokobil'skiy, A.I.; Kharabadze, N.E.; Shonia, N.I.; Desai, L.S.; Foley, G.E.

    1976-01-01

    The results of the determination of trace elements in nucleic acids and histones in human leukaemic cells by activation analysis are reported. The Cr 2+ , Fe 2+ , Zn 2+ , Co 2+ and Sb 2+ content of DNA and RNA of leukaemic cells compared to that of lymphocytes from a patient with infectious mononucleosis or a normal donor are shown tabulated. Similar comparisons are shown for the same trace metal content of histones isolated from the same type of cells. It is felt that the results afford further interesting speculation that trace metals may be involved in the interactions between histones and DNA (especially at the binding sites of histones to DNA), which affect transcription characteristics. (U.K.)

  14. Prognosis of Primary and Recurrent Chondrosarcoma of the Rib.

    Science.gov (United States)

    Roos, Eva; van Coevorden, Frits; Verhoef, Cornelis; Wouters, Michel W; Kroon, Herman M; Hogendoorn, Pancras C W; van Houdt, Winan J

    2016-03-01

    Chondrosarcoma of the rib is a rare disease. Although surgery is the only curative treatment option, rib resection with an adequate margin can be challenging and local recurrence is a frequent problem. In this study, the prognosis of primary and recurrent chondrosarcoma of the rib is reported. Retrospective analysis was performed of patients treated for chondrosarcoma of the rib between 1984 and 2014 in three major tertiary referral centers in The Netherlands. Clinical and histopathological features were analyzed for their prognostic value using Kaplan-Meier and Cox proportional hazard analysis. Endpoints were set at local recurrent disease, metastasis rate, or death. Overall, 76 patients underwent a resection for a primary chondrosarcoma, and 26 patients underwent a resection for a recurrent chondrosarcoma. Five-year overall survival in the primary group was 90%, local recurrence rate was 17%, and metastasis rate was 12%. The 5-year outcome after recurrent chondrosarcoma was lower, with an overall survival of 65%, local recurrence rate of 27%, and metastasis rate of 27%. For primary chondrosarcoma, tumor size >5 cm and a positive resection margin were correlated with worse overall survival [hazard ratio (HR) 3.28, 95% confidence interval (CI) 1.03-10.44; HR 2.92, 95% CI 1.03-8.25). A higher histological grade was correlated with a higher local recurrence and metastasis rate (HR 5.92, 95% CI 1.11-31.65; HR 6.96, 95% CI 1.15-42.60). Surgical resection of both primary and recurrent chondrosarcoma of the rib is an effective treatment strategy. The oncological outcome after surgery is worse in tumors >5 cm, in tumors with positive resection margins and grade 3 chondrosarcoma.

  15. Human leukaemic cells

    International Nuclear Information System (INIS)

    Andronikashvili, E.L.; Mosulishvili, L.M.; Belokobil'skiy, A.I.; Kharabadze, N.E.; Shonia, N.I.; Desai, L.S.; Foley, G.E.

    1976-01-01

    Trace metals were measured by neutron-activation analyses in purified nucleic acids and histone(s) of lymphocytes from patients with acute lymphocytic leukaemia or infectious mononucleosis, and from normal donors. DNA isolated from lymphocytes of a patient with infectious mononucleosis and a normal donor showed a high content of Cr 2+ , Sb 2+ , Fe 2+ , Zn 2+ , whereas DNA of lymphoblasts from a patient with acute lymphocytic leukaemia had a lower content of these trace metals, but the Co 2+ content was 20-fold higher than in DNA of normal donor lymphocytic cells. Total histones from leukaemic cells had higher contents of most of the trace metals except for Zn 2+ , which was present in lesser concentration than in histones from normal donor lymphocytic cells. Lysine-rich (F1) histones showed lower contents of Cr 2+ , Sb 2+ and Co 2+ , whereas arginine-rich (F3) histones had significantly higher contents of these trace metals. These observations may be of interest in that F3 histones more effectively inhibit RNA synthesis in human lymphocytic cells than do other species of histones. (author)

  16. High-energy irradiation in the management of chondrosarcoma

    International Nuclear Information System (INIS)

    Kim, R.Y.; Salter, M.M.; Brascho, D.J.

    1983-01-01

    We present a retrospective analysis of seven patients with chondrosarcoma of the bone treated by high-energy irradiation between 1961 and 1976. Its major role in this series was prevention of local recurrence in cases with inadequate resection. In three of the five cases in which radiation therapy was adjuvant rather than primary treatment, long-term local control was obtained in a dose of 5,000 to 6,500 rads in five to six weeks. Although primary treatment of chondrosarcoma is surgical, high-dose radiation therapy is indicated when surgical resection is not possible. Chondrosarcoma can respond to high doses of irradiation even though the response is slow

  17. Role of radionuclide imaging in the diagnosis of chondrosarcoma

    International Nuclear Information System (INIS)

    McLean, R.G.; Choy, D.; Hoeschl, R.; Nayanar, V.; Murray, I.P.

    1985-01-01

    The diagnosis of chondrosarcoma may be difficult if there is an atypical radiographic appearance or an inconclusive biopsy. Radionuclide bone scans of 13 patients with chondrosarcoma were reviewed to assess if a pattern of scan features could be recognized in association with this tumor. A combination, including increased blood pool activity, moderate intensity of uptake, patchy uptake with cortical predominance of activity, minimal distortion of bony outline, and a well-defined scintigraphic margin, occurred regularly in the series. Recognition of this characteristic pattern of scintigraphic features in cases of suspected chondrosarcoma may assist in the diagnostic assessment

  18. Synovial chondrosarcoma: Report of two cases and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Zamora, E.E. [Department of Orthopaedic Surgery, Hospital Dr. R.A Calderon Guardia, Universidad De Costa Rica, P.O. Box 628-3000, Heredia (Costa Rica); Musculoskeletal Oncology Department, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna (Italy); Mansor, A. [Musculoskeletal Oncology Department, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna (Italy); Department of Orthopaedic Surgery, University of Malaya, Kuala Lumpur 59100 (Malaysia); Vanel, D. [Musculoskeletal Oncology Research Center, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna (Italy)], E-mail: dvanel@ior.it; Errani, C.; Mercuri, M. [Musculoskeletal Oncology Department, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna (Italy); Picci, P. [Musculoskeletal Oncology Research Center, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna (Italy); Alberghini, M. [Musculoskeletal Anatomical Pathology Department, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna (Italy)

    2009-10-15

    Synovial chondrosarcoma is a rare soft tissue tumor that can arise from a previous synovial chondromatosis or as de novo tumor. The clinical and radiological findings of this malignancy are very similar to those of aggressive synovial chondromatosis. Confusion with other joint pathologies makes the diagnosis of synovial chondrosarcoma difficult in most of the cases. We present one recently diagnosed and treated case of synovial chondrosarcoma. The review of our hospital database revealed one more similar case. In both cases the malignancy arose from a pre-existing synovial chondromatosis. We also present a literature review emphasizing the clinical and histological findings of this rare entity.

  19. What Is New in the miRNA World Regarding Osteosarcoma and Chondrosarcoma?

    Science.gov (United States)

    Palmini, Gaia; Marini, Francesca; Brandi, Maria Luisa

    2017-03-07

    Despite the availability of multimodal and aggressive therapies, currently patients with skeletal sarcomas, including osteosarcoma and chondrosarcoma, often have a poor prognosis. In recent decades, advances in sequencing technology have revealed the presence of RNAs without coding potential known as non-coding RNAs (ncRNAs), which provides evidence that protein-coding genes account for only a small percentage of the entire genome. This has suggested the influence of ncRNAs during development, apoptosis and cell proliferation. The discovery of microRNAs (miRNAs) in 1993 underscored the importance of these molecules in pathological diseases such as cancer. Increasing interest in this field has allowed researchers to study the role of miRNAs in cancer progression. Regarding skeletal sarcomas, the research surrounding which miRNAs are involved in the tumourigenesis of osteosarcoma and chondrosarcoma has rapidly gained traction, including the identification of which miRNAs act as tumour suppressors and which act as oncogenes. In this review, we will summarize what is new regarding the roles of miRNAs in chondrosarcoma as well as the latest discoveries of identified miRNAs in osteosarcoma.

  20. MRI features of extraskeletal myxoid chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-01-01

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

  1. Radionuclide bone scanning of medullary chondrosarcoma

    International Nuclear Information System (INIS)

    Hudson, T.M.; Chew, F.S.; Manaster, B.J.

    1982-01-01

    Technetium-99m methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan intake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the ''extended pattern of uptake'' beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogenous uptake on the scan

  2. Radionuclide bone scanning of medullary chondrosarcoma

    International Nuclear Information System (INIS)

    Hudson, T.M.; Chew, F.S.; Manaster, B.J.

    1982-01-01

    /sup 99m/Tc methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan uptake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the extended pattern of uptake beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogeneous uptake on the scan

  3. Radiological features of 24 periosteal chondrosarcomas

    International Nuclear Information System (INIS)

    Vanel, D.; De Paolis, M.; Mercuri, M.; Monti, C.; Picci, P.

    2001-01-01

    Objective. To report the imaging findings of 24 periosteal chondrosarcomas diagnosed, staged, treated and followed in a single institution, to analyze and define their pattern, and discuss their practical consequences.Design and patients. Plain films, 16 CT examinations and four MRI examinations were reviewed, and compared with the histological evaluation.Results. There were 20 men and four women, aged from 17 to 65 years. Twelve lesions involved the distal femoral metaphyses (8 posteriorly), five the proximal humerus, two the proximal metaphyses of the femur and two of the tibia, two the humeral shafts and one the iliac wing. Size varied from 4 to 11 cm. The cortex was always involved (thick, 15; thin, 13). Typical cartilaginous calcifications and cartilaginous lobules were very frequent. Radial thick periosteal bone formations (n=6) indicated calcifications between the lobules of cartilage. Medullary involvement was rare (n=2). All patients are alive and free of disease.Conclusions. Recognizing periosteal chondrosarcoma is of paramount importance because the prognosis is excellent after adequate local surgery alone. The patterns of other surface tumors of bone are usually different. (orig.)

  4. Indications to radical surgical interventions in chondrosarcomas of the limbs

    International Nuclear Information System (INIS)

    Korolev, V.I.

    1988-01-01

    On the basis of analysis carried out in treatment of 229 patients suffering from chondrosarcomas of the limbs it is established that radical surgical intervention in bulk of amputation or exarticulation is the choice of the treatment method at the 3d clinical stage of disease. Sex does not influence the chondrosarcomas prognosis. 20-years age patients have the shortest life-time after operation. Radiotherapy and chemotherapy does not improve the results of surgical treatment

  5. Conservative cricoid surgery for chondrosarcoma: a case report.

    Science.gov (United States)

    Gaio, Elena; Maggiore, Giandomenico; Canesso, Alessandra; Artico, Riccardo

    2014-02-01

    We present the case of a 39-year-old man who presented with hoarseness and progressively worsening dyspnea. Findings on laryngoscopy and computed tomography strongly suggested the presence of a chondrosarcoma. The patient underwent open surgery for removal of the lesion with wide margins. Reconstruction was carried out with two segments of costal cartilage. Laryngeal chondrosarcomas are rare, malignant, usually well-differentiated neoplasms that should be treated with conservative surgery. Recurrences should be treated more aggressively.

  6. Chondrosarcoma occurring in a patient with polyostotic fibrous dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    De Smet, A.A.; Travers, H.; Neff, J.R.

    1981-12-01

    A 36-year-old white man with polyostotic fibrous dysplasia was found to have a high-grade chondrosarcoma arising from the left ilium. Although a left hemipelvectomy was performed, the patient subsequently developed sacral and pulmonary metastases and succumbed to his disease. This patient represents the first documented example of an unequivocally high-grade chondrosarcoma arising in an area of fibrous dysplasia without prior irradiation.

  7. Periosteal chondrosarcoma: a histopathological and molecular analysis of a rare chondrosarcoma subtype.

    Science.gov (United States)

    Cleven, Arjen H G; Zwartkruis, Evita; Hogendoorn, Pancras C W; Kroon, Herman M; Briaire-de Bruijn, Inge; Bovée, Judith V M G

    2015-10-01

    Periosteal chondrosarcoma is a rare, malignant cartilage-forming neoplasm originating from the periosteal surface of bone. We collected 38 cases from the archives of the Netherlands Committee on Bone Tumours, with the aim of studying histological features and evaluating the involvement of isocitrate dehydrogenase 1 (IDH1), EXT, Wnt/β-catenin, the pRB pathway (CDK4 and p16), and the TP53 pathway (p53 and MDM2). Histology showed a moderately cellular matrix with mucoid-myxoid changes and, in 42% of cases, formation of a neocortex. Occasional intramedullary extension (26%) and subsequent host bone entrapment (40%) were seen. Histological grading revealed grade 1 (53%) and grade 2 (45%). The EXT1 protein was normally expressed, and mutations in IDH1 were observed in only 15% of cases. pRb signalling was deregulated by loss of p16 expression in 50% of cases, and Wnt signalling was lost in 89%. No alterations were found in CDK4, p53, or MDM2. We report the first large histological and molecular study on periosteal chondrosarcoma showing that histopathological examination and molecular aberrations do not predict prognosis. Although the mutation frequency of IDH1 was low, we confirm the supposed relationship with central chondrosarcoma. Moreover, we identify loss of canonical Wnt signalling and deregulation of pRb signalling as possible events contributing to its histogenesis. © 2015 John Wiley & Sons Ltd.

  8. The Identification of Prognostic Factors and Survival Statistics of Conventional Central Chondrosarcoma

    NARCIS (Netherlands)

    Nota, Sjoerd P. F. T.; Braun, Yvonne; Schwab, Joseph H.; van Dijk, C. Niek; Bramer, Jos A. M.

    2015-01-01

    Introduction. Chondrosarcomas are malignant bone tumors that are characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effect on chondrosarcoma, treatment of most patients depends on surgical resection. We conducted this study to identify

  9. Genome engineering in human cells.

    Science.gov (United States)

    Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

    2014-01-01

    Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

  10. Laryngeal Chondrosarcoma: An Exceptional Localisation of a Not Unfrequent Bone Tumor

    Directory of Open Access Journals (Sweden)

    Mieke Moerman

    2009-01-01

    Full Text Available After osteosarcoma, chondrosarcoma is the second most common primary bone tumor accounting for 26% of all malignancies. In the laryngeal region however, chondrosarcomas are rather rare. Only 300 cases are reported in literature. Considering laryngeal chondrosarcoma, about 75% occur in the cricoid cartilage, whereas 20% occur in the thyroid cartilage. In this paper we report a case of thyroidal chondrosarcoma, and based on a thorough literature search we suggest some practical guidelines concerning diagnosis and therapy.

  11. Primary Spinal Chondrosarcoma: Radiologic Findings with Pathologic Correlation

    Energy Technology Data Exchange (ETDEWEB)

    Lloret, I.; Server, A. [The Norwegian Radium Hospital, Oslo (Norway). Depts. of Radiology and Pathology; Bjerkehagen, B. [Ullevaal Univ. Hospital, Oslo (Norway). Dept. of Neuroradiology

    2006-02-15

    Purpose: To describe the radiologic appearance of the four types of primary spinal chondrosarcoma (CHS) (conventional intramedullary, juxtacortical, clear cell, and mesenchymal) and to correlate with histopathologic findings. Material and Methods: A retrospective review was carried out of 5 patients with histopathologically confirmed primary spinal CHS; 3 F and 2 M ranging in age between 27 and 66 years (mean 40.2; median 39). Charts, conventional radiographs, computed tomography scans, and magnetic resonance images were reviewed. All the patients underwent surgical excision, followed by postoperative chemotherapy (1 patient) and radiotherapy (3 patients). Follow-up was available for all patients but one. The mean follow-up was 42 months (14-120 months). Histopathological specimens for all patients were available for review. Results: Vertebral column distribution was 3 thoracic (60%), 1 cervical (20%), and 1 lumbar (20%). Neurological deficits were present in 3 (60%) cases. The radiological appearance of the four types of primary spinal CHS varies with specific lesion type. Imaging findings suggest diagnosis of the conventional intramedullary and juxtacortical types. While the clear cell and mesenchymal types show some distinctive features, these do not allow confident radiologic diagnosis. Conclusion: The radiologist must be aware of imaging features of these tumors in order to improve diagnostic accuracy, treatment planning, and prognosis.

  12. Primary Spinal Chondrosarcoma: Radiologic Findings with Pathologic Correlation

    International Nuclear Information System (INIS)

    Lloret, I.; Server, A.; Bjerkehagen, B.

    2006-01-01

    Purpose: To describe the radiologic appearance of the four types of primary spinal chondrosarcoma (CHS) (conventional intramedullary, juxtacortical, clear cell, and mesenchymal) and to correlate with histopathologic findings. Material and Methods: A retrospective review was carried out of 5 patients with histopathologically confirmed primary spinal CHS; 3 F and 2 M ranging in age between 27 and 66 years (mean 40.2; median 39). Charts, conventional radiographs, computed tomography scans, and magnetic resonance images were reviewed. All the patients underwent surgical excision, followed by postoperative chemotherapy (1 patient) and radiotherapy (3 patients). Follow-up was available for all patients but one. The mean follow-up was 42 months (14-120 months). Histopathological specimens for all patients were available for review. Results: Vertebral column distribution was 3 thoracic (60%), 1 cervical (20%), and 1 lumbar (20%). Neurological deficits were present in 3 (60%) cases. The radiological appearance of the four types of primary spinal CHS varies with specific lesion type. Imaging findings suggest diagnosis of the conventional intramedullary and juxtacortical types. While the clear cell and mesenchymal types show some distinctive features, these do not allow confident radiologic diagnosis. Conclusion: The radiologist must be aware of imaging features of these tumors in order to improve diagnostic accuracy, treatment planning, and prognosis

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

    Directory of Open Access Journals (Sweden)

    Priya Rao

    2014-12-01

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

  14. Long-term Outcome of Chondrosarcoma: A Single Institutional Experience.

    Science.gov (United States)

    Bindiganavile, Srimanth; Han, Ilkyu; Yun, Ji Yeon; Kim, Han-Soo

    2015-10-01

    The prognostic factors of chondrosarcoma remain uncertain as only a few large studies with long-term follow-up have been reported. The aim of this study was to analyze oncological outcomes and prognostic factors. A retrospective review of oncological outcomes and prognostic factors was performed on 125 consecutive chondrosarcoma patients who underwent surgery at our institution. Overall survival was 91.6%±2.5%, 84.1%±3.8%, and 84.1%±3.8% at 5, 10, and 15 years respectively. Among the histological types, dedifferentiated type showed the worst survival (p chondrosarcoma, histologic grade and anatomical location predicted outcome, with high-grade with axial location having the worst outcome (p chondrosarcoma of appendicular skeleton could be treated safely by intralesional curettage. Histological type was significantly associated with the outcome of chondrosarcoma. For the conventional type, histologic grade and anatomical location predicted outcome, with high-grade with axial location having the worst outcome.

  15. Primary Extraskeletal Mesenchymal Chondrosarcoma Arising from the Pancreas

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-12-15

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

  16. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self......-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number...

  17. Human innate lymphoid cells

    NARCIS (Netherlands)

    Hazenberg, Mette D.; Spits, Hergen

    2014-01-01

    Innate lymphoid cells (ILCs) are lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity and tissue remodeling. ILCs are categorized into 3 groups based on their distinct patterns of cytokine production and the requirement of

  18. Human innate lymphoid cells

    NARCIS (Netherlands)

    Mjösberg, Jenny; Spits, Hergen

    2016-01-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune

  19. Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  20. Primary extraskeletal mesenchymal chondrosarcoma arising from the iliac vein

    Directory of Open Access Journals (Sweden)

    Hua Zhang

    2017-10-01

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

  1. Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-09-15

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

  2. CT and MRI diagnosis of chondrosarcoma in sinonasal and orbital region

    International Nuclear Information System (INIS)

    Yang Bentao; Wang Zhenchang; Xian Junfang; Zhang Zhengyu; Liu Zhonglin; Lan Baosen

    2006-01-01

    Objective: To investigate the CT and MRI findings of chondrosarcoma in sinonasal and orbital region so as to promote the diagnostic accuracy. Methods: All 12 cases of chondrosarcoma were verified by pathology. CT and MRI findings were analyzed retrospectively. Results: The lesions occurred in sinonasal cavity in 9 cases and in orbit in 3 cases. Pathologically 8 cases were conventional chondrosarcoma, 2 dedifferentiated chondrosarcoma, and 2 mesenchymal chondrosarcoma. On CT, chondrosarcoma revealed oval shape in 2 cases, lobular shape in 6 cases and irregular shape in 4 cases. The lesion showed stippled, ring, nodular, patchy or amorphous calcification. Postcontrast CT showed mild inhomogeneous enhancement in 3 cases. Chondrosarcoma demonstrated well-defined margin in 9 cases and hazy margin in 3 cases. Sinonasal chondrosarcoma revealed bony destruction in 7 cases. Orbital chondrosarcoma showed bony erosion invading ipsilateral frontal region in one case. On MR T 1 WI, conventional and dedifferentiated chondrosarcoma showed hypointense signal compared to brain in 6 cases and isointense signal in 4 cases. On T 2 WI, the lesions showed heterogeneous hyperintense signal in 8 cases and isointense signal in 2 cases with marked hypointense foci. Postcontrast MR imaging demonstrated mild to moderate inhomogeneous enhancement in these cases, and showed peripheral and septal enhancement in 5 cases of conventional chondrosarcoma, showing variegated appearance in 3 cases and honeycomb-like appearance in 2 cases. Mesenchymal chondrosarcoma showed isointense signal on both T 1 WI and T 2 WI, with homogeneous and heterogeneous enhancement in one case, respectively. MRI showed the extent and the associated changes of the lesions more clearly compared to CT. Conclusion: CT is the first modality of choice in the diagnosis of chondrosarcoma in sinonasal and orbital region. The typically peripheral and septal contrast enhancement can also suggest the diagnosis of chondrosarcoma on

  3. Can imaging criteria distinguish enchondroma from grade 1 chondrosarcoma?

    Science.gov (United States)

    Crim, Julia; Schmidt, Robert; Layfield, Lester; Hanrahan, Christopher; Manaster, Betty Jean

    2015-11-01

    To minimize systematic bias and optimize agreement on imaging criteria in order to better define the accuracy of imaging criteria in the diagnosis of grade 1 chondrosarcoma. Study was IRB-approved and HIPAA compliant; informed consent was waived. Records were reviewed and disclosed 53 cases (38 women, 15 men ages 21-76) which were diagnosed as enchondroma or grade 1 chondrosarcoma and had available radiographs, contrast-enhanced MRI, and definitive diagnosis by histology or 5-year follow-up. 2 MSK radiologists read the studies independently after a session where they agreed on criteria for malignancy. Interobserver variability was determined as raw variability and with the kappa statistic. Accuracy was determined compared to final diagnosis. Reliability of imaging features of chondrosarcoma was determined using regression analysis. The correct diagnosis of enchondroma was made on radiographs in 43 (67.2%) of readings, and on MRI in 37/64 (57.8%). The correct diagnosis of chondrosarcoma was made on radiographs in 5/24 (20.8%) of readings, and on MRI in 14/24 (57.8%). A diagnosis of borderline lesion was made in 19/64 (29.7%) of enchondromas on radiographs and 18/64 (28.1%) on MRI. The false positive rate of radiographs for chondrosarcoma was 2/64 (3.1%) and the false positive rate of MRI was 9/64 (14.1%). There was substantial interobserver variability. Cortical thickening and bone expansion were rare but specific signs of chondrosarcoma. Both radiographs and MRI have limitations in the evaluation of low-grade cartilage lesions. MRI has an increased rate of both true-positive and false-positive diagnosis compared to radiographs. Differences in the findings of this study compared to previous literature may reflect the influence of systematic biases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Primary intradural mesenchymal chondrosarcoma of the spine in a child

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yu-Hua [Shanghai Jiao Tong University, Department of Radiology, Xin Hua Hospital, School of Medicine, Shanghai (China); Yao, Xiao-Hong [Shanghai Jiao Tong University, Department of Pathology, Xin Hua Hospital, School of Medicine, Shanghai (China)

    2007-11-15

    We report a primary intradural mesenchymal chondrosarcoma of the spine in a 3-year-old girl. MRI revealed a markedly enhancing oval mass associated with focal areas of low signal intensity extending from T11 to L1. The lesion was located posterolateral to the right side of the spinal cord, pushing the conus medullaris and cauda equina anteriorly and to the left. The adjacent spinal cord also showed serpiginous areas of flow void. The mass was completely removed. Microscopic examination and immunohistochemical studies confirmed the diagnosis of mesenchymal chondrosarcoma. The patient was free of symptoms after surgery. (orig.)

  5. Chondrosarcoma of the hyoid bone: computed tomography findings

    International Nuclear Information System (INIS)

    Saez, J.; Gallego, J. a.; Fuster, M. J.

    2001-01-01

    Chondrosarcoma of the hyoid bone is a rare entity, only 10 cases of which have been reported in the literature to date. the case we present involved a 24-year-old man who complained of progressive adynophagia and a mass in anterior neck. Computed tomography revealed a low-attenuation mas attached to the left horn of the hyoid bone. The lesion was excised and was diagnosed as a grade II chondrosarcoma. The patient remains asymptomatic 10 years after the operation. (Author) 11 refs

  6. Giant Sacral Chondrosarcoma in an Elderly Male : A Case Report

    Directory of Open Access Journals (Sweden)

    HZ Chan

    2014-03-01

    Full Text Available Primary sacral tumours are rare, therefore experience of managing their associated complications are very limited. Effective surgical treatment of pelvic chondrosarcoma remains a major challenge for orthopaedic surgeons, due to the complex anatomic structure of the pelvis, the lack of defined compartment borders, the close vicinity to vital structures, and the risk of jeopardizing pelvic structural stability. We report a rare case of a giant sacral chondrosarcoma (100cm x 80cm in an elderly male who successfully underwent tumour resection with good functional outcome and recovery. Long term follow up is essential in view of the possibility of local tumour recurrence.

  7. A chondrosarcoma in the anterior mediastinum mimicking a thymoma

    International Nuclear Information System (INIS)

    Østergaard, Mia L; Petersen, Rene H; Kalhauge, Anna

    2015-01-01

    A chondrosarcoma in the anterior mediastinum is a rare finding with a relatively good prognosis. We describe a case of a 75-year-old man with a 2-year history of neck discomfort and weight loss. Imaging showed a homogenous tumor with a minor compression on the anterior part of the heart. It had close relation to the ribs, no surrounding fat, and a thymoma was suspected. Biopsy prior to surgery was impossible due to the location of the tumor. Unfortunately, final pathology from the surgical specimen revealed a chondrosarcoma

  8. Primary intradural mesenchymal chondrosarcoma of the spine in a child

    International Nuclear Information System (INIS)

    Li, Yu-Hua; Yao, Xiao-Hong

    2007-01-01

    We report a primary intradural mesenchymal chondrosarcoma of the spine in a 3-year-old girl. MRI revealed a markedly enhancing oval mass associated with focal areas of low signal intensity extending from T11 to L1. The lesion was located posterolateral to the right side of the spinal cord, pushing the conus medullaris and cauda equina anteriorly and to the left. The adjacent spinal cord also showed serpiginous areas of flow void. The mass was completely removed. Microscopic examination and immunohistochemical studies confirmed the diagnosis of mesenchymal chondrosarcoma. The patient was free of symptoms after surgery. (orig.)

  9. Laryngeal chondrosarcoma - Ten years of experience

    Directory of Open Access Journals (Sweden)

    José Fernando dos Santos Oliveira

    2014-07-01

    Full Text Available INTRODUCTION: Laryngeal involvement by cartilaginous tumors is rare. However, although accounting for only 1% of laryngeal tumor pathology, they are the most frequently occurring non-epithelial neoplasms. The most probable location is the endolaryngeal surface of the cricoid cartilage. Their symptoms are variable, depending on the size and location, and may include hoarseness, stridor, and dyspnea. Treatment is based on surgical excision. Some centers take into account the degree of differentiation and whether it is a case of relapse when deciding to perform a radical resection. AIM: To evaluate this disease in a sample of the Portuguese population. METHODS: A review of the medical records from 2002 to 2012 by assessment of clinical processes was performed. Data on demographics, clinical treatments, and outcomes were collected. RESULTS: Six patients were included in the study. Five of them underwent total laryngectomy, and in one case, partial excision of the thyroid cartilage was performed. None of the patients had either metastases or tumor-related death. CONCLUSION: Laryngeal chondrosarcomas remain a rare disease of unknown etiology, with slow and insidious symptoms. The treatment is surgical, with favorable prognosis, and metastases rarely occur. The main concern regards their propensity to relapse.

  10. Stimulated human fibroblast cell survival

    International Nuclear Information System (INIS)

    Smith, B.P.; Gale, K.L.; Einspenner, M.; Greenstock, C.L.; Gentner, N.E.

    1992-01-01

    Techniques for cloning cultured mammalian cells have supported the most universally-accepted method for measuring the induction of lethality by geno-toxicants such as ionizing radiation: the 'survival of colony-forming ability (CFA)' assay. Since most cultured human cell lines exhibit plating efficiency (i.e. the percentage of cells that are capable of reproductively surviving and dividing to form visible colonies) well below 100%, such assays are in essence 'survival of plating efficiency' assays, since they are referred to the plating (or cloning) efficiency of control (i.e. unirradiated) cells. (author). 8 refs., 2 figs

  11. Human embryonic stem cells handbook

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2013-03-01

    Full Text Available After the Nobel prize in physiology or medicine was awarded jointly to Sir John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent it became imperative to write down the review for a book entirely devoted to human embryonic stem cells (hES, those cells that are a urgent need for researchers, those cells that rekindle the ethical debates and finally, last but not least, those cells whose study paved the way to obtain induced pluripotent stem cells by the OSKC’s Yamanaka method (the OSKC acronim refers, for those not familiar with the topic, to the four stemness genes used to transfect somatic fibroblasts: Oct4, Sox2, Klf4 and c-Myc....

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

    Directory of Open Access Journals (Sweden)

    Ricardo Balanzá, MD

    2016-01-01

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

  13. Hip-sparing approach using computer navigation in periacetabular chondrosarcoma

    NARCIS (Netherlands)

    Gerbers, J. G.; Jutte, P. C.

    2013-01-01

    Chondrosarcoma of the pelvis is difficult to treat due to the anatomical location and the high incidence of recurrence. Treatment is primarily surgical, and the surgical margins, based on MSTS criteria, have been shown to be predictive of disease recurrence and mortality. However, too-wide margins

  14. Case report 517: Mesenchymal chondrosarcoma of the femur

    International Nuclear Information System (INIS)

    Bertoni, F.; Bacchini, P.; Picci, P.; Gherlinzoni, F.

    1989-01-01

    This case confirms that mesenchymal chondrosarcoma, a highly malignant tumor, may have a protracted clinical course. The radiographic presentation, as in this case, may be misleading since the small size of the lesion and the apparently well marginated lytic zone could easily suggest a benign lesion. (orig./GDG)

  15. Chondrosarcoma in a wild great white heron from southern Florida.

    Science.gov (United States)

    Spalding, M G; Woodard, J C

    1992-01-01

    A typical chondrosarcoma is reported from the nictitating membrane of a great white heron (Ardea herodius occidentalis). This is the first report of a neoplasm in a free flying ciconiiform, and was the only one found in a survey of 957 carcasses from Florida.

  16. Extraskeletal myxoid chondrosarcoma: tumor response to sunitinib

    Directory of Open Access Journals (Sweden)

    Stacchiotti Silvia

    2012-10-01

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

  17. Analysis of radiological features relative to pathology in pelvic chondrosarcoma

    International Nuclear Information System (INIS)

    Zhou Jianjun; Ding Jianguo; Wang Jianhua; Zeng Mengsu; Yan Fuhua; Zhou Kangrong; Ji Yuan

    2008-01-01

    Objective: To Explore the imaging features relative to pathology of pelvic chondrosarcoma and to evaluate the clinical value. Methods: All 12 cases patients with primary pelvic chondrosarcoma confirmed by pathological examination underwent radiography, spiral CT plain scanning, MR SE-T 1 WI, FSE-T 2 WI and SE-T 1 WI enhancement scanning before operation. The imaging data was reviewed and analyzed retrospectively to compare with surgical and pathological results. Results: Eleven conventional chondrosarcoma and one dedifferentiated chondrosarcoma were located in different parts of pelvis. The diameters of the tumors ranged from 4.7 to 17.0 cm with one case less than 5.0 cm, 6 cases being 5.0-10.0 cm and 5 cases more than 10.0 cm. The CT value of 5 eases was identical or inferior to muscle with mild to moderate 'ring-and-arc' mineralization and soft mass. MR imaging depict the high water content of these lesions as very high signal intensity was detected on T 2 WI. Six cases showed typical 'ting- and-arc' fibrous tissue which enhanced persistently. Aggressive features of deep endosteal scalloping and soft-tissue extension was also found in these cases. Conclusions: Radiographic findings can suggest the diagnosis of pelvic chondrosarcoma when there is typical 'ring-and-arc' fibrous tissue, mineralization, aggressive features of deep endosteal scalloping and large soft-tissue extension. MR imaging reflect directly this pathologic structure, superior to that of CT and radiography. CT is optimal to detect the matrix mineralization, particularly when it is subtle or when the lesion is located in anatomically complex pelvic areas. (authors)

  18. Cranial computed tomographic appearance of chondrosarcoma of the base of the skull

    International Nuclear Information System (INIS)

    Grossman, R.I.; Davis, K.R.

    1981-01-01

    Five patients with a histologic diagnosis of chondrosarcoma are discussed, with special attention to evaluation of these lesions by cranial computed tomography (CCT). These patients displayed findings that are highly suggestive of chondrosarcoma: high absorption abnormality on plain CCT scans, contrast enhancement, and osteolytic changes of the contiguous bone. Treatment consisted of surgery and subsequent radiation therapy. CCT played an important part in diagnosing and determining the extent of the chondrosarcomas

  19. MRI differentiation of low-grade from high-grade appendicular chondrosarcoma

    International Nuclear Information System (INIS)

    Douis, Hassan; Singh, Leanne; Saifuddin, Asif

    2014-01-01

    To identify magnetic resonance imaging (MRI) features which differentiate low-grade chondral lesions (atypical cartilaginous tumours/grade 1 chondrosarcoma) from high-grade chondrosarcomas (grade 2, grade 3 and dedifferentiated chondrosarcoma) of the major long bones. We identified all patients treated for central atypical cartilaginous tumours and central chondrosarcoma of major long bones (humerus, femur, tibia) over a 13-year period. The MRI studies were assessed for the following features: bone marrow oedema, soft tissue oedema, bone expansion, cortical thickening, cortical destruction, active periostitis, soft tissue mass and tumour length. The MRI-features were compared with the histopathological tumour grading using univariate, multivariate logistic regression and receiver operating characteristic curve (ROC) analyses. One hundred and seventy-nine tumours were included in this retrospective study. There were 28 atypical cartilaginous tumours, 79 grade 1 chondrosarcomas, 36 grade 2 chondrosarcomas, 13 grade 3 chondrosarcomas and 23 dedifferentiated chondrosarcomas. Multivariate analysis demonstrated that bone expansion (P = 0.001), active periostitis (P = 0.001), soft tissue mass (P < 0.001) and tumour length (P < 0.001) were statistically significant differentiating factors between low-grade and high-grade chondral lesions with an area under the ROC curve of 0.956. On MRI, bone expansion, active periostitis, soft tissue mass and tumour length can reliably differentiate high-grade chondrosarcomas from low-grade chondral lesions of the major long bones. (orig.)

  20. Cytological diagnosis of chondrosarcoma: A case report with review of literature

    Directory of Open Access Journals (Sweden)

    Karuna Daswani

    2015-01-01

    Full Text Available Chondrosarcoma is a malignant tumor of bone showing cartilaginous differentiation. Fine needle aspiration cytology (FNAC is found to be effective in the preoperative diagnosis of chondrosarcoma combined with radiological and clinical evaluation. Ribs is one of the most common skeleton sites for chondrosarcoma, the others being pelvis, proximal femur, proximal humerus and distal femur. We are presenting the case of a 40-year-old man who presented with a tumor in the anterior chest wall on the left side. On FNAC of the mass, a diagnosis of low-grade chondrosarcoma was made which was later confirmed on histopathology.

  1. MRI differentiation of low-grade from high-grade appendicular chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Douis, Hassan; Singh, Leanne; Saifuddin, Asif [The Royal National Orthopaedic Hospital NHS Trust, Department of Radiology, Stanmore, Middlesex (United Kingdom)

    2014-01-15

    To identify magnetic resonance imaging (MRI) features which differentiate low-grade chondral lesions (atypical cartilaginous tumours/grade 1 chondrosarcoma) from high-grade chondrosarcomas (grade 2, grade 3 and dedifferentiated chondrosarcoma) of the major long bones. We identified all patients treated for central atypical cartilaginous tumours and central chondrosarcoma of major long bones (humerus, femur, tibia) over a 13-year period. The MRI studies were assessed for the following features: bone marrow oedema, soft tissue oedema, bone expansion, cortical thickening, cortical destruction, active periostitis, soft tissue mass and tumour length. The MRI-features were compared with the histopathological tumour grading using univariate, multivariate logistic regression and receiver operating characteristic curve (ROC) analyses. One hundred and seventy-nine tumours were included in this retrospective study. There were 28 atypical cartilaginous tumours, 79 grade 1 chondrosarcomas, 36 grade 2 chondrosarcomas, 13 grade 3 chondrosarcomas and 23 dedifferentiated chondrosarcomas. Multivariate analysis demonstrated that bone expansion (P = 0.001), active periostitis (P = 0.001), soft tissue mass (P < 0.001) and tumour length (P < 0.001) were statistically significant differentiating factors between low-grade and high-grade chondral lesions with an area under the ROC curve of 0.956. On MRI, bone expansion, active periostitis, soft tissue mass and tumour length can reliably differentiate high-grade chondrosarcomas from low-grade chondral lesions of the major long bones. (orig.)

  2. What are the differentiating clinical and MRI-features of enchondromas from low-grade chondrosarcomas?

    Energy Technology Data Exchange (ETDEWEB)

    Douis, Hassan [Royal Orthopaedic Hospital, Department of Radiology, Birmingham (United Kingdom); University Hospital Birmingham, Department of Radiology, Birmingham (United Kingdom); Parry, M. [Royal Orthopaedic Hospital, Department of Orthopaedic Oncology, Birmingham (United Kingdom); Vaiyapuri, S. [Royal Orthopaedic Hospital, Department of Musculoskeletal Pathology, Birmingham (United Kingdom); Davies, A.M. [Royal Orthopaedic Hospital, Department of Radiology, Birmingham (United Kingdom)

    2018-01-15

    To evaluate the role of clinical assessment, conventional and dynamic contrast-enhanced MRI in differentiating enchondromas from chondrosarcomas of long bone. The following clinical and MRI findings were assessed: age, gender, pain, pain attributable to lesion, tumour location, tumour length, presence, depth of endosteal scalloping, bone marrow oedema, soft tissue oedema, cortical destruction, periosteal reaction, bone expansion, macroscopic fat, calcification, soft tissue mass, haemorrhage, dynamic contrast-enhanced MRI. Clinical and MRI findings were compared with histopathological grading. Sixty patients with central chondroid tumours were included (27 enchondromas, 10 cartilaginous lesions of unknown malignant potential, 15 grade 1 chondrosarcomas, 8 high-grade chondrosarcomas). Pain attributed to lesion, tumour length, endosteal scalloping > 2/3, cortical destruction, bone expansion and soft tissue mass were differentiating features between enchondromas and grade 1 chondrosarcomas. Dynamic contrast-enhanced MRI could not differentiate enchondromas from grade 1 chondrosarcomas. Previously reported imaging signs of chondrosarcomas are useful in the diagnosis of grade 1 lesions but have lower sensitivity than in higher grade lesions. Deep endosteal scalloping is the most sensitive imaging sign of grade 1 chondrosarcomas. Pain due to the lesion is an important clinical sign of grade 1 chondrosarcomas. Dynamic contrast-enhanced MRI is not useful in differentiating enchondromas from grade 1 chondrosarcomas. (orig.)

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

    Science.gov (United States)

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

    2016-11-10

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

  4. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    OpenAIRE

    Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

    1988-01-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting f...

  5. Concurrent periosteal chondroma and enchondroma of the fibula mimicking chondrosarcoma

    International Nuclear Information System (INIS)

    Yamamoto, Yasuhiro; Washimi, Osuke; Yamada, Harumoto; Washimi, Yuki; Itoh, Masato; Kuroda, Makoto

    2006-01-01

    We present a rare concurrence of enchondroma and periosteal chondroma in the right distal fibula that mimicked chondrosarcoma in a 13-year-old boy. Radiographs and CT scans showed a periosteal lesion producing saucerization without periosteal reaction and calcification in the distal metaphysis of the right fibula. MRI showed an intramedullary lesion adjacent to the periosteal lesion, although it was invisible at CT. There was no cortical breach on imaging and gross examination. Because both lesions represented benign cartilaginous tumors on histology, concurrent periosteal chondroma and enchondroma of the fibula was diagnosed. This combination in the same bone in a patient without enchondromatosis is exceedingly rare. Such imaging features may be confused with those of chondrosarcoma. (orig.)

  6. Clinicopathologic correlation of chondrosarcoma of mandible with a case report

    Directory of Open Access Journals (Sweden)

    Sanchita Kundu

    2011-01-01

    Full Text Available Chondrosarcoma is a rare primary malignant neoplasm of the head, neck, oral and maxillofacial regions. The clinicopathological and radiographic findings are usually characteristic; however, not decisive. The neoplasm is usually treated by wide surgical resection because it is traditionally radioresistant. However, radiotherapy is generally advised for high-grade lesions, and chemotherapy has a palliative role. The treatment and management are primarily guided by the histological grades of the neoplasm. Prognosis of jaw lesions is poor as compared to the lesions affecting the long bones of the body, and the cause of death is usually by direct extension in the base of the skull or due to distant metastasis to lungs and other bones. A clinical case of chondrosarcoma, involving the right half of mandible of a 36 year old male patient is discussed herewith, encompassing the entire gamut of clinicopathological, radiological and treatment modalities rendered.

  7. Primary chondrosarcoma of the trachea with extensive extraluminal growth.

    Science.gov (United States)

    Ryabov, Andrey; Pikin, Oleg; Sokolov, Victor; Volchenko, Nadezda

    2017-09-01

    Primary chondrosarcoma of the trachea is an extremely rare non-epithelial neoplasm with only few cases published in the literature. We present a rare case of tracheal chondrosarcoma with extensive extraluminal growth. We operated a patient with obstructive tumour of the upper third of the trachea via partial sternotomy. Before surgery, a Hanarostent was put into the trachea to treat a life-threatening stenosis. Postoperative period was uneventful. We discuss the incidence, clinical presentation and treatment options in patients with rare tracheal tumours. In some cases, a multidisciplinary approach (endoscopic intervention followed by surgical resection) is an effective treatment tool. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  8. Concurrent periosteal chondroma and enchondroma of the fibula mimicking chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Yasuhiro; Washimi, Osuke; Yamada, Harumoto; Washimi, Yuki; Itoh, Masato [Fujita Health University, Department of Orthopedic Surgery, Toyoake City, Aichi (Japan); Kuroda, Makoto [Fujita Health University, Department of Pathology, Toyoake City, Aichi (Japan)

    2006-05-15

    We present a rare concurrence of enchondroma and periosteal chondroma in the right distal fibula that mimicked chondrosarcoma in a 13-year-old boy. Radiographs and CT scans showed a periosteal lesion producing saucerization without periosteal reaction and calcification in the distal metaphysis of the right fibula. MRI showed an intramedullary lesion adjacent to the periosteal lesion, although it was invisible at CT. There was no cortical breach on imaging and gross examination. Because both lesions represented benign cartilaginous tumors on histology, concurrent periosteal chondroma and enchondroma of the fibula was diagnosed. This combination in the same bone in a patient without enchondromatosis is exceedingly rare. Such imaging features may be confused with those of chondrosarcoma. (orig.)

  9. X-ray images in primary bone chondrosarcoma

    International Nuclear Information System (INIS)

    Syrtmadzhieva, S.; Andreev, I.; Velichkov, L.

    1982-01-01

    The X-ray images of primary bone chondrosarcomas in 76 patients are reviewed. The tumors have been localized largely in the long tubular bones - in some patients centrally or excentrically, in others superficially. The X-ray images presented with osteolytic, osteoplastic and mixed changes, intratumor calcifications and reactive bone and periosteal changes. The presence of any of these changes and their combinations, depending on the localization and the influence of a variety of other factors, resembled much many other primary and metastatic malignant bone tumors, benign bone tumors and tumor-like diseases. The X-ray images showed a major complexity in the development of the primary chondrosarcoma and its relations with the bone as organ. (author)

  10. Human glomerular epithelial cell proteoglycans

    International Nuclear Information System (INIS)

    Thomas, G.J.; Jenner, L.; Mason, R.M.; Davies, M.

    1990-01-01

    Proteoglycans synthesized by cultures of human glomerular epithelial cells have been isolated and characterized. Three types of heparan sulfate were detected. Heparan sulfate proteoglycan I (HSPG-I; Kav 6B 0.04) was found in the cell layer and medium and accounted for 12% of the total proteoglycans synthesized. HSPG-II (Kav 6B 0.25) accounted for 18% of the proteoglycans and was located in the medium and cell layer. A third population (9% of the proteoglycan population), heparan sulfate glycosaminoglycan (HS-GAG; Kav 6B 0.4-0.8), had properties consistent with single glycosaminoglycan chains or their fragments and was found only in the cell layer. HSPG-I and HSPG-II from the cell layer had hydrophobic properties; they were released from the cell layer by mild trypsin treatment. HS-GAG lacked these properties, consisted of low-molecular-mass heparan sulfate oligosaccharides, and were intracellular. HSPG-I and -II released to the medium lacked hydrophobic properties. The cells also produced three distinct types of chondroitin sulfates. The major species, chondroitin sulfate proteoglycan I (CSPG-I) eluted in the excluded volume of a Sepharose CL-6B column, accounted for 30% of the proteoglycans detected, and was found in both the cell layer and medium. Cell layer CSPG-I bound to octyl-Sepharose. It was released from the cell layer by mild trypsin treatment. CSPG-II (Kav 6B 0.1-0.23) accounted for 10% of the total 35S-labeled macromolecules and was found predominantly in the culture medium. A small amount of CS-GAG (Kav 6B 0.25-0.6) is present in the cell extract and like HS-GAG is intracellular. Pulse-chase experiments indicated that HSPG-I and -II and CSPG-I and -II are lost from the cell layer either by direct release into the medium or by internalization where they are metabolized to single glycosaminoglycan chains and subsequently to inorganic sulfate

  11. Laryngeal Chondrosarcoma: A rare cause of critical upper airway obstruction.

    LENUS (Irish Health Repository)

    Tuite, K

    2018-01-01

    Laryngeal cancers are rare, encompassing around one percent of all cancers. Suspicion should be raised if a patient presents with classical signs and symptoms; i.e. dysphonia, inspiratory stridor, dysphagia, odynophagia, neck mass, or persistent cough. Laryngeal chondrosarcoma is a rare form of laryngeal cancer, the diagnosis of which can be difficult. The case in question describes an unusual presentation of one such case, and its subsequent investigation, management and outcome.

  12. Laryngeal chondrosarcoma: A systematic review of 592 cases.

    Science.gov (United States)

    Chin, Oliver Y; Dubal, Pariket M; Sheikh, Ahmed B; Unsal, Aykut A; Park, Richard Chan Woo; Baredes, Soly; Eloy, Jean Anderson

    2017-02-01

    Laryngeal chondrosarcomas are rare entities that arise from the cartilaginous structures of the larynx, including the cricoid, thyroid cartilage, epiglottis, and arytenoid cartilages. These tumors represent a minority of malignancies involving the larynx and can be mistaken for benign pathologies. The treatment has historically been surgical excision, often by total laryngectomy. This review investigates treatment modalities and patient outcomes. Systematic review using PubMed/MEDLINE and EMBASE database. The databases were used to identify articles reporting cases of chondrosarcomas occurring exclusively in the larynx. Variables analyzed included patient demographics, presenting symptoms, grade, therapeutic approach, patient outcomes, and follow-up. Five hundred and ninety-two cases were identified. The average age reported was 62.5 years. There was a 3:1 male to female ratio. The most common surgical approach was local excision in 178 cases, followed by total laryngectomy in 174 cases. Nonsurgical treatment such as radiotherapy and chemotherapy was only used in 0.8% and 0.2%, respectively. Disease-specific survival rates for 1, 5, 10, and 20 years were 97.7%, 91.4%, 81.8%, and 68.0%, respectively, with no differences when comparing 5-year survival rates for location, grade, and therapy. Laryngeal chondrosarcomas are rare with a good prognosis. Various surgical approaches exist, with no difference noted in 5-year survival outcomes. Nonsurgical approaches were rarely used for these lesions. N/A. Laryngoscope, 2016 127:430-439, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Case report: Chondrosarcoma of the head and neck

    Directory of Open Access Journals (Sweden)

    Francisco Carlos Quevedo, MD

    2017-03-01

    Full Text Available Chondrosarcoma originates in the bones of the head and neck. It is an unusual neoplasm that is slow-growing and represents only 1–3% of all cases of chondrosarcoma. Here, we report a case of a 45-year-old male Caucasian patient treated at Hospital Amaral Carvalho with a history of swelling of the face and a tumoral mass in the right maxilla with infiltration into the skin, which had been present for 4 months. A computerized tomography (CT of the face and sinuses demonstrated a lesion in the right maxilla. A maxilectomia without orbital exenteration was performed. It was diagnosed as a grade III chondrosarcoma, with infiltration into the subjacent bone, anterior wall of the maxillary sinus and floor of the orbit. The patient presented with recurrence of the tumor after adjuvant therapies. A molecular study on the present case showed an unusually large number of abnormalities. This finding demonstrated extreme chromosomal instability, which was likely due to the undifferentiation of the tumor. Although there are no cases in the literature with which to compare, these findings may elucidate potential therapeutic targets for advanced tumors without other therapeutic options.

  14. DNA repair in human cells

    International Nuclear Information System (INIS)

    Regan, J.D.; Carrier, W.L.; Kusano, I.; Furuno-Fukushi, I.; Dunn, W.C. Jr.; Francis, A.A.; Lee, W.H.

    1982-01-01

    Our primary objective is to elucidate the molecular events in human cells when cellular macromolecules such as DNA are damaged by radiation or chemical agents. We study and characterize (i) the sequence of DNA repair events, (ii) the various modalities of repair, (iii) the genetic inhibition of repair due to mutation, (iv) the physiological inhibition of repair due to mutation, (v) the physiological inhibition of repair due to biochemical inhibitors, and (vi) the genetic basis of repair. Our ultimate goals are to (i) isolate and analyze the repair component of the mutagenic and/or carcinogenic event in human cells, and (ii) elucidate the magnitude and significance of this repair component as it impinges on the practical problems of human irradiation or exposure to actual or potential chemical mutagens and carcinogens. The significance of these studies lies in (i) the ubiquitousness of repair (most organisms, including man, have several complex repair systems), (ii) the belief that mutagenic and carcinogenic events may arise only from residual (nonrepaired) lesions or that error-prone repair systems may be the major induction mechanisms of the mutagenic or carcinogenic event, and (iii) the clear association of repair defects and highly carcinogenic disease states in man [xeroderma pigmentosum (XP)

  15. No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone

    NARCIS (Netherlands)

    Peterse, E.F.P.; Cleven, A.H.G.; Jong, de Y.; Briaire-de, Bruijn I.; Fletcher, J.A.; Danen, E.H.J.; Cleton, A.M.; Bov'ee, J.V.M.G.

    2016-01-01

    Background Chondrosarcoma is a malignant cartilage forming bone tumour for which no effective systemic treatment is available. Previous studies illustrate the need for a better understanding of the role of the IGF pathway in chondrosarcoma to determine if it can be a target for therapy, which was

  16. Myxoid chondrosarcoma in the calcaneus: a case report with MR imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jong Won; Kwack, Kyu-Sung [Seoul National University Bundang Hospital, Department of Radiology, Seong Nam, Gyeongi-Do (Korea); Choi, Jung-Ah; Kang, Heung Sik [Seoul National University Bundang Hospital, Department of Radiology, Seong Nam, Gyeongi-Do (Korea); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea); Oh, Joo Han [Seoul National University Bundang Hospital, Department of Orthopedic Surgery, Seong Nam, Gyeongi-Do (Korea); Chung, Jin Haeng [Seoul National University Bundang Hospital, Department of Pathology, Seong Nam, Gyeongi-Do (Korea)

    2007-06-15

    Skeletal myxoid chondrosarcoma is an extraordinarily rare neoplasm with a distinct histological morphology. Herein, we report a case of a myxoid chondrosarcoma in the calcaneus of a 20-year-old man with a description of its MR imaging (MRI) and histological findings. (orig.)

  17. Mesenchymal chondrosarcoma arising from the intrascrotal extratesicular soft tissue;a case report

    International Nuclear Information System (INIS)

    Lim, Jong-Uk; Koo, Bong-Sik; Park, Byeong-Ho; Park, Chang-Sook; Nam, Kyung-Jin; Kweon, Heon-Young

    2000-01-01

    Intrascrotal extratesticular malignancies are rare, and the radiologic findings of extraskeletal chondrosarcoma have not been reported. We describe the radiologic findings of a case of mesenchymal chondrosarcoma arising from intrascrotal extratesticular soft tissue and represented by a complex, cystic, solid mass containing calcifications and hematoma

  18. Recurrent primary lumbar vertebra chondrosarcoma: Marginal resection and Iodine-125 seed therapy

    Directory of Open Access Journals (Sweden)

    Chunpeng Ren

    2014-01-01

    Full Text Available Chondrosarcomas are uncommon in the spinal column. En bloc excisions with wide margins are of critical importance but not always feasible in spine. We report the outcome in a case of recurrent lumbar vertebral chondrosarcoma treated with marginal resection and iodine-125 seeds placed in the resected tumor bed.

  19. Chondrosarcoma of the temporomandibular joint: a case report and review of the literature.

    Science.gov (United States)

    Oh, Kyu-Young; Yoon, Hye-Jung; Lee, Jae-Il; Hong, Sam-Pyo; Hong, Seong-Doo

    2016-07-01

    Chondrosarcoma is the second most common sarcoma arising in the bone, but it rarely involves the temporomandibular joint (TMJ). To date, 30 cases of TMJ chondrosarcoma have been reported in the English literature, and the authors report an additional case arising from a cystic lesion in a 60-year-old female patient. The clinical and radiological diagnosis of the lesion was initially synovial cyst, and periodic check-ups were done after aspiration of the lesion. After three years, the patient perceived swelling of the lesion, and surgical excision was performed. The final diagnosis was grade I chondrosarcoma. When clinicians detect a cystic lesion in the radiographic imaging of the TMJ, chondrosarcoma should be included in the differential diagnosis. In addition, computed tomography (CT) as well as magnetic resonance imaging (MRI) is recommended for the accurate diagnosis and proper preoperative planning in TMJ chondrosarcoma.

  20. The human airway epithelial basal cell transcriptome.

    Directory of Open Access Journals (Sweden)

    Neil R Hackett

    2011-05-01

    Full Text Available The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population.Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels.The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium.

  1. A Prospective Outcomes Study of Proton Therapy for Chordomas and Chondrosarcomas of the Spine

    Energy Technology Data Exchange (ETDEWEB)

    Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org [Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States); Rotondo, Ronny L.; Begosh-Mayne, Dustin [Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States); Scarborough, Mark T.; Gibbs, C. Parker [Department of Orthopedics and Rehabilitation, University of Florida College of Medicine, Gainesville, Florida (United States); Morris, Christopher G.; Mendenhall, William M. [Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States)

    2016-05-01

    Purpose: To evaluate the effectiveness of definitive or adjuvant external beam proton therapy on survival in patients with chordomas and chondrosarcomas of the spine. Methods and Materials: Between March 2007 and May 2013, 51 patients with a median age of 58 years (range, 22-83 years) with chordoma (n=34) or chondrosarcomas (n=17) of the sacrum (n=21), the cervical spine (n=20), and the thoracolumbar spine (n=10) were treated with external beam proton therapy to a median dose of 70.2 Gy(RBE) [range, 64.2-75.6 Gy(RBE)] at our institution. Distant metastases, overall survival, cause-specific survival, local control, and disease-free survival were calculated. Results: The mean follow-up time was 3.7 years (range, 0.3-7.7 years). Across all time points, 25 patients experienced disease recurrence: 18 local recurrences, 6 local and distant recurrences, and 1 distant metastasis. The 4-year rates of overall survival and cause-specific survival were 72%; disease-free survival was 57%, local control was 58%, and freedom from distant metastases was 86%. The median time to local progression was 1.7 years (range, 0.2-6.0 years), and the median time to distant progression was 1.6 years (range, 0.2-6.0 years). The risk factors for local recurrence were age ≤58 years (62% vs 26%; P=.04) and recurrence after prior surgery (29% vs 81%; P=.01). Secondary cancers developed in 2 patients: B-cell lymphoma 5.5 years after treatment and bladder cancer 2 years after treatment. We observed the following toxicities: sacral soft tissue necrosis requiring surgery (n=2), T1 vertebral fracture requiring fusion surgery (n=1), chronic urinary tract infections (n=1), surgery for necrotic bone cyst (n=1), and grade 2 bilateral radiation nephritis (n=1). Conclusion: High-dose proton therapy controls more than half of spinal chordomas and chondrosarcomas and compares favorably with historic photon data. Local progression is the dominant mode of treatment failure and may be reduced by

  2. Human regulatory B cells control the TFH cell response.

    Science.gov (United States)

    Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

    2017-07-01

    Follicular helper T (T FH ) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of T FH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on T FH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate T FH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing T FH cell maturation. In cocultures they differentiated B cells into CD138 + plasma and IgD - CD27 + memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented T FH cell development. Added to T FH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3 + CXCR5 + PD-1 + follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on T FH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control T FH cell maturation, expand follicular regulatory T cells, and inhibit the T FH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the T FH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. Endocannabinoids and Human Sperm Cells

    Directory of Open Access Journals (Sweden)

    Giovanna Zolese

    2010-10-01

    Full Text Available N-acylethanolamides (NAEs are naturally occurring signaling lipids consisting of amides and esters of long-chain polyunsaturated fatty acids. Usually they are present in a very small amounts in many mammalian tissues and cells, including human reproductive tracts and fluids. Recently, the presence of N-arachidonoylethanolamide (anandamide, AEA, the most characterised member of endocannabinoids, and its congeners palmitoylethanolamide (PEA and oleylethanolamide (OEA in seminal plasma, oviductal fluid, and follicular fluids was demonstrated. AEA has been shown to bind not only type-1 (CB1 and type-2 (CB2 cannabinoid receptors, but also type-1 vanilloid receptor (TRPV1, while PEA and OEA are inactive with respect to classical cannabinoid CB1 and CB2 but activate TRPV1 or peroxisome proliferator activate receptors (PPARs. This review concerns the most recent experimental data on PEA and OEA, endocannabinoid-like molecules which appear to exert their action exclusively on sperm cells with altered features, such as membrane characteristics and kinematic parameters. Their beneficial effects on these cells could suggest a possible pharmacological use of PEA and OEA on patients affected by some forms of idiopathic infertility.

  4. Gamma Knife surgery for intracranial chordoma and chondrosarcoma: radiosurgical perspectives and treatment outcomes.

    Science.gov (United States)

    Kim, Ji Hee; Jung, Hyun Ho; Chang, Jong Hee; Chang, Jin Woo; Park, Yong Gou; Chang, Won Seok

    2014-12-01

    Intracranial chordomas and chondrosarcomas are histologically low-grade, locally invasive tumors that are reported to be similar in terms of anatomical location, clinical presentation, and radiological findings but different in terms of behavior and outcomes. The purpose of this study was to investigate and compare clinical outcomes after Gamma Knife surgery (GKS) for the treatment of intracranial chordoma and chondrosarcoma. The authors conducted a retrospective review of the results of radiosurgical treatment of intracranial chordomas and chondrosarcomas. They enrolled patients who had undergone GKS for intracranial chordoma or chondrosarcoma at the Yonsei Gamma Knife Center, Yonsei University College of Medicine, from October 2000 through June 2007. Analyses included only patients for whom the disease was pathologically diagnosed before GKS and for whom more than 5 years of follow-up data after GKS were available. Rates of progression-free survival and overall survival were analyzed and compared according to tumor pathology. Moreover, the association between tumor control and the margin radiation dose to the tumor was analyzed, and the rate of tumor volume change after GKS was quantified. A total of 10 patients were enrolled in this study. Of these, 5 patients underwent a total of 8 sessions of GKS for chordoma, and the other 5 patients underwent a total of 7 sessions of GKS for chondrosarcoma. The 2- and 5-year progression-free survival rates for patients in the chordoma group were 70% and 35%, respectively, and rates for patients in the chondrosarcoma group were 100% and 80%, respectively (log-rank test, p = 0.04). The 2- and 5-year overall survival rates after GKS for patients in the chordoma group were 87.5% and 72.9%, respectively, and rates for patients in the chondrosarcoma group were 100% and 100%, respectively (log-rank test, p = 0.03). The mean rates of tumor volume change 2 years after radiosurgery were 79.64% and 39.91% for chordoma and

  5. Stem cells in the human breast

    DEFF Research Database (Denmark)

    Petersen, Ole William; Polyak, Kornelia

    2010-01-01

    The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main...... mammary cell lineages, producing an increasing number of cells with distinct properties. Understanding the biological characteristics of human breast stem cells and their progeny is crucial in attempts to compare the features of normal stem cells and cancer precursor cells and distinguish these from...... nonprecursor cells and cells from the bulk of a tumor. A historical overview of research on human breast stem cells in primary tissue and in culture reveals the progress that has been made in this area, whereas a focus on the cell-of-origin and reprogramming that occurs during neoplastic conversion provides...

  6. Dedifferentiated chondrosarcoma: Radiological features, prognostic factors and survival statistics in 23 patients

    Science.gov (United States)

    Liu, Chenglei; Xi, Yan; Li, Mei; Jiao, Qiong; Zhang, Huizhen; Yang, Qingcheng; Yao, Weiwu

    2017-01-01

    Background Dedifferentiated chondrosarcoma is a rare, highly malignant tumor with a poor survival. There are many confusing issues concerning the imaging feature that can facilitate early diagnosis and the factors that might be related to outcomes. Methods Twenty-three patients with dedifferentiated chondrosarcoma confirmed by pathology were retrospectively reviewed from 2008 to 2015. The patients’ clinical information, images from radiographs (n = 17), CT (n = 19), and MRI (n = 17), histological features, treatment and prognosis were analyzed. Results There were 12 males and 11 females, and the mean age was 50.39 years old. Fourteen cases affected the axial bone (pelvis, spine), and 9 cases involved the appendicular bone. Seven (41.17%), 9 (47.36), and 12 (66.66%) lesions showed a biphasic nature on radiograph, CT and MRI, respectively. Of the lesions, 17.39% (4/23) were accompanied by pathological fractures. Histologically, the cartilage component was considered histological Grade1 in 12 patients and Grade 2 in 11 patients. The dedifferentiated component showed features of osteosarcoma in 8 cases, malignant fibrous histiocytoma in3 cases, myofibroblastic sarcoma in 1 case and spindle cell sarcoma in 11cases. Twenty-two cases were treated with surgical resection, and 17 cases achieved adequate (wide or radical) surgical margin. In 8 cases, surgery was combined with adjuvant chemotherapy. The overall median survival time was nine months; 17.4% of patients survived to five years. Conclusion Axial bone location, lung metastasis at diagnosis, inadequate surgical margin, incorrect diagnosis before surgery and pathological fractures was related to poorer outcome. Pre- or postoperative chemotherapy had no definitively effect on improved survival. PMID:28301537

  7. Satellite cells in human skeletal muscle plasticity.

    Science.gov (United States)

    Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

    2015-01-01

    Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  8. Chondrosarcoma of the Proximal Phalanx of the Fourth Digit: A Rare Location

    Directory of Open Access Journals (Sweden)

    Thivi Vasilakaki

    2012-10-01

    Full Text Available Introduction: Cartilaginous tumors involving the small bones of the hands and feet are usually benign such as enchondroma, chondromyxoid fibroma and chondroblastoma. The small bones of the hands and feet are rarely involved by primary chondrosarcoma. Proximal phalanges are the most common sites in the hands, but the fourth digit is the least common site. Case Presentation: We report a case of a 76-year-old Greek female who presented to our hospital with a painful swollen mass measuring 4.5 × 2.6 cm on the fourth digit of the left hand. The radiograph showed a destructive, permeative lytic tumor of the proximal phalanx with extension into soft tissue. The patient underwent curettage, and the microscopic examination of the specimen revealed grade 2 chondrosarcoma. Conclusion: Cartilaginous tumors involving the small bones of the hands and feet are usually benign such as enchondroma, chondromyxoid fibroma and chondroblastoma. Primary chondrosarcoma is the third most common malignancy of bone after myeloma and osteosarcoma, but the small bones of the hands and feet are very rarely involved by chondrosarcoma (1% of all chondrosarcoma. However, in these cases differentiation between a benign lesion and chondrosarcoma may be difficult. Occasionally chondrosarcoma of the hands and feet is associated with multiple recurrences or distal metastasis.

  9. c-Myc-Dependent Cell Competition in Human Cancer Cells.

    Science.gov (United States)

    Patel, Manish S; Shah, Heta S; Shrivastava, Neeta

    2017-07-01

    Cell Competition is an interaction between cells for existence in heterogeneous cell populations of multicellular organisms. This phenomenon is involved in initiation and progression of cancer where heterogeneous cell populations compete directly or indirectly for the survival of the fittest based on differential gene expression. In Drosophila, cells having lower dMyc expression are eliminated by cell competition through apoptosis when present in the milieu of cells having higher dMyc expression. Thus, we designed a study to develop c-Myc (human homolog) dependent in vitro cell competition model of human cancer cells. Cells with higher c-Myc were transfected with c-myc shRNA to prepare cells with lower c-Myc and then co-cultured with the same type of cells having a higher c-Myc in equal ratio. Cells with lower c-Myc showed a significant decrease in numbers when compared with higher c-Myc cells, suggesting "loser" and "winner" status of cells, respectively. During microscopy, engulfment of loser cells by winner cells was observed with higher expression of JNK in loser cells. Furthermore, elimination of loser cells was prevented significantly, when co-cultured cells were treated with the JNK (apoptosis) inhibitor. Above results indicate elimination of loser cells in the presence of winner cells by c-Myc-dependent mechanisms of cell competition in human cancer cells. This could be an important mechanism in human tumors where normal cells are eliminated by c-Myc-overexpressed tumor cells. J. Cell. Biochem. 118: 1782-1791, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Signaling hierarchy regulating human endothelial cell development.

    Science.gov (United States)

    Kelly, Melissa A; Hirschi, Karen K

    2009-05-01

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

  11. Radiographic differentiation of enchondroma from low-grade chondrosarcoma in the fibula

    Energy Technology Data Exchange (ETDEWEB)

    Kendell, Scott D. [Department of Radiology, Duke University, Box 3808, 27710, Durham, North Carolina (United States); Department of Radiology E-2, Mayo Clinic, 200 First Street, 55905, SW Rochester, Minnesota (United States); Collins, Mark S.; Adkins, Mark C.; Sundaram, Murali; Unni, Krishnan K. [Department of Radiology E-2, Mayo Clinic, 200 First Street, 55905, SW Rochester, Minnesota (United States)

    2004-08-01

    To evaluate demographic and radiographic features that may differentiate between enchondroma and low-grade chondrosarcoma of the fibula. The radiographs of ninety-three histologically-confirmed cartilaginous tumors of the fibula were retrospectively reviewed along with demographic information as to patient age and gender. Fifty-four enchondromas and thirty-nine low-grade chondrosarcomas were included in the study. Multiple previously-established radiographic features distinguishing enchondroma from chondrosarcoma were evaluated in each fibular tumor in a consensus manner by two experienced, board-certified and fellowship-trained musculoskeletal radiologists. Five radiographic features were shown to statistically favor chondrosarcoma over enchondroma in the fibula. These were soft-tissue mass (p<0.0001), periosteal reaction (p=0.008), cortical disruption in the juxta-articular fibula (p=0.0133), cortical thickening (p=0.032), and tumor size greater than 4 cm (p=0.0046). No statistically-significant demographic differences were found between patients with enchondroma and chondrosarcoma of the fibula. When two or more of the identified features of malignancy are identified in the same patient, chondrosarcoma is 2.4 times more likely than in those patients exhibiting none of the features of malignancy. Soft-tissue mass, periosteal reaction, cortical disruption in the juxta-articular fibula, cortical thickening, and tumor size greater than 4 cm indicate chondrosarcoma over enchondroma of the fibula. Radiographs demonstrating more than one of the identified malignant features are more likely to be due to chondrosarcoma than radiographs demonstrating none or only one of the identified features. No unique malignant features of chondrosarcoma in the fibula were observed when compared to previous descriptions of these tumors in the long and short tubular bones of the appendicular skeleton. (orig.)

  12. Radiographic differentiation of enchondroma from low-grade chondrosarcoma in the fibula

    International Nuclear Information System (INIS)

    Kendell, Scott D.; Collins, Mark S.; Adkins, Mark C.; Sundaram, Murali; Unni, Krishnan K.

    2004-01-01

    To evaluate demographic and radiographic features that may differentiate between enchondroma and low-grade chondrosarcoma of the fibula. The radiographs of ninety-three histologically-confirmed cartilaginous tumors of the fibula were retrospectively reviewed along with demographic information as to patient age and gender. Fifty-four enchondromas and thirty-nine low-grade chondrosarcomas were included in the study. Multiple previously-established radiographic features distinguishing enchondroma from chondrosarcoma were evaluated in each fibular tumor in a consensus manner by two experienced, board-certified and fellowship-trained musculoskeletal radiologists. Five radiographic features were shown to statistically favor chondrosarcoma over enchondroma in the fibula. These were soft-tissue mass (p<0.0001), periosteal reaction (p=0.008), cortical disruption in the juxta-articular fibula (p=0.0133), cortical thickening (p=0.032), and tumor size greater than 4 cm (p=0.0046). No statistically-significant demographic differences were found between patients with enchondroma and chondrosarcoma of the fibula. When two or more of the identified features of malignancy are identified in the same patient, chondrosarcoma is 2.4 times more likely than in those patients exhibiting none of the features of malignancy. Soft-tissue mass, periosteal reaction, cortical disruption in the juxta-articular fibula, cortical thickening, and tumor size greater than 4 cm indicate chondrosarcoma over enchondroma of the fibula. Radiographs demonstrating more than one of the identified malignant features are more likely to be due to chondrosarcoma than radiographs demonstrating none or only one of the identified features. No unique malignant features of chondrosarcoma in the fibula were observed when compared to previous descriptions of these tumors in the long and short tubular bones of the appendicular skeleton. (orig.)

  13. Analysis of radiological features relative to histopathology in 42 skull-base chordomas and chondrosarcomas

    International Nuclear Information System (INIS)

    Pamir, M. Necmettin; Ozduman, Koray

    2006-01-01

    Chordomas and chondrosarcomas are malignant tumors that are reported to have similar clinical presentations and radiological features but different behaviors and outcomes. The aim of this retrospective study was to determine whether specific radiological features of skull-base chordomas or chondrosarcomas are correlated with histopathology, and thus allow preoperative diagnosis. The study involved 32 classic chordomas, 6 chondroid chordomas and 4 chondrosarcomas (42 tumors total). For each case, tumor size and extent, the detailed anatomy involved, and magnetic resonance imaging and computed tomography findings were analyzed. Tumor extent was assessed using a novel method that assessed presence/absence in 18 defined skull-base zones. The chondrosarcomas presented significantly earlier in life than the chordomas (means, 20.5 years versus 36 years, respectively). At time of diagnosis, the median tumor volume was 23 cm 3 (range, 1.2-78.8 cm 3 ) and the mean tumor extent was 6.7 ± 2.9 zones. There were no differences between chordomas and chondrosarcomas, or between the two chordoma subgroups, with respect to lesion volume or extent. Comparison of other imaging findings revealed no features that were diagnostic for either chordoma or chondrosarcoma. The data support previous claims that chondrosarcomas present earlier in life than chordomas, but this finding is not diagnostic. There is wide variation in the extent of skull-base chordomas and chondrosarcomas, and in the specific anatomical structures these tumors involve. None of the MRI or CT features of these tumors appear to be useful for differentiating chordomas from chondrosarcomas preoperatively. For surgical planning, specific, area-oriented definition of tumor extent might provide more useful information than tumor-type classification schemes

  14. Is bone scintigraphy necessary in the initial surgical staging of chondrosarcoma of bone?

    Energy Technology Data Exchange (ETDEWEB)

    Douis, Hassan; James, Steven L.; Davies, Mark A. [Royal Orthopaedic Hospital, Department of Radiology, Birmingham (United Kingdom); Grimer, Robert J. [Royal Orthopaedic Hospital, Department of Orthopaedic Oncology, Birmingham (United Kingdom)

    2012-04-15

    To assess the value of whole-body bone scintigraphy in the initial surgical staging of chondrosarcoma of bone. A retrospective review was conducted of the bone scintigraphy reports of a large series of patients with peripheral or central chondrosarcoma of bone treated in a specialist orthopaedic oncology unit over a 13-year period. Abnormal findings were correlated against other imaging, histological grade and the impact on surgical staging. A total of 195 chondrosarcomas were identified in 188 patients. In 120 (63.8%) patients the reports of bone scintigraphy noted increased activity at the site of one or more chondrosarcomas. In one patient the tumour was outside the field-of-view of the scan, and in the remaining 67 (35.6%) cases, there was increased activity at the site of the chondrosarcoma and further abnormal activity in other areas of the skeleton. Causes of these additional areas of activity included degenerative joint disease, Paget's disease and in one case a previously undiagnosed melanoma metastasis. No cases of skeletal metastases from the chondrosarcoma were found in this series. Multifocal chondrosarcomas were identified in three cases. In two it was considered that all the tumours would have been adequately revealed on the initial MR imaging staging studies. In only the third multifocal case was an unsuspected, further presumed low-grade, central chondrosarcoma identified in the opposite asymptomatic femur. Although this case revealed an unexpected finding the impact on surgical staging was limited as it was decided to employ a watch-and-wait policy for this tumour. There is little role for the routine use of whole-body bone scintigraphy in the initial surgical staging in patients with chondrosarcoma of bone irrespective of the histological grade. (orig.)

  15. Analysis of radiological features relative to histopathology in 42 skull-base chordomas and chondrosarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Pamir, M. Necmettin [Marmara University Faculty of Medicine, Department of Neurosurgery, Istanbul (Turkey)]. E-mail: koray.ozduman@yale.edu; Ozduman, Koray [Marmara University Faculty of Medicine, Department of Neurosurgery, Istanbul (Turkey)

    2006-06-15

    Chordomas and chondrosarcomas are malignant tumors that are reported to have similar clinical presentations and radiological features but different behaviors and outcomes. The aim of this retrospective study was to determine whether specific radiological features of skull-base chordomas or chondrosarcomas are correlated with histopathology, and thus allow preoperative diagnosis. The study involved 32 classic chordomas, 6 chondroid chordomas and 4 chondrosarcomas (42 tumors total). For each case, tumor size and extent, the detailed anatomy involved, and magnetic resonance imaging and computed tomography findings were analyzed. Tumor extent was assessed using a novel method that assessed presence/absence in 18 defined skull-base zones. The chondrosarcomas presented significantly earlier in life than the chordomas (means, 20.5 years versus 36 years, respectively). At time of diagnosis, the median tumor volume was 23 cm{sup 3} (range, 1.2-78.8 cm{sup 3}) and the mean tumor extent was 6.7 {+-} 2.9 zones. There were no differences between chordomas and chondrosarcomas, or between the two chordoma subgroups, with respect to lesion volume or extent. Comparison of other imaging findings revealed no features that were diagnostic for either chordoma or chondrosarcoma. The data support previous claims that chondrosarcomas present earlier in life than chordomas, but this finding is not diagnostic. There is wide variation in the extent of skull-base chordomas and chondrosarcomas, and in the specific anatomical structures these tumors involve. None of the MRI or CT features of these tumors appear to be useful for differentiating chordomas from chondrosarcomas preoperatively. For surgical planning, specific, area-oriented definition of tumor extent might provide more useful information than tumor-type classification schemes.

  16. Desmoid tumor of bone with enchondromatous nodules, mistaken for chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Won-Jong [Musculoskeletal Oncology Study Group, Catholic University of Korea (Korea); Department of Orthopaedic Surgery, Uijongbu St. Mary' s Hospital, 65-1 Geumohdong, Uijongbu, Gyunggido, 480-130 (Korea); Kang, Yong-Koo; Lee, An-Hee [Musculoskeletal Oncology Study Group, Catholic University of Korea (Korea); Mirra, Joseph M. [Orthpaedic Oncology, Orthopaedic Hospital, Los Angeles, CA (United States)

    2003-04-01

    Desmoid tumor of bone, also termed desmoplastic fibroma or aggressive fibromatosis, is a rare, locally aggressive fibroblastic tumor. We present a 16-year-old male with a huge desmoid tumor involving the iliac wing. It was associated with enchondromatous nodules mimicking malignancy. The tumor in this patient was mistaken for chondrosarcoma and hemipelvectomy was performed. To our knowledge, such a case has not previously been documented fully in the English literature. The radiographic and pathologic findings and a possible mechanism of enchondromatous nodule formation in fibrous bone tumors are discussed. (orig.)

  17. Laryngeal Chondrosarcoma as a Rare Cause of Subglottic Stenosis

    Directory of Open Access Journals (Sweden)

    Kerem Kökoğlu

    2014-01-01

    Full Text Available Laryngeal chondrosarcoma (CS is a very rare entity. It is usually seen in 50–80-year olds. It is developed from cricoid cartilage largely. Patients have laryngeal CS complaint of respiratuvar distress, dysphonia, and dysphagia generally. A submucous mass is usually seen in physical examination with an intact mucosa. Distant metastasis is rare in CSs. Main treatment is surgical excision. An 82-year-old patient who has respiratuvar distress is presented in this paper and laryngeal CS is reviewed in the light of the literature.

  18. Symmetry breaking in human neuroblastoma cells

    Science.gov (United States)

    Izumi, Hideki; Kaneko, Yasuhiko

    2014-01-01

    Asymmetric cell division (ACD) is a characteristic of cancer stem cells, which exhibit high malignant potential. However, the cellular mechanisms that regulate symmetric (self-renewal) and asymmetric cell divisions are mostly unknown. Using human neuroblastoma cells, we found that the oncosuppressor protein tripartite motif containing 32 (TRIM32) positively regulates ACD. PMID:27308367

  19. Trophoblast lineage cells derived from human induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Wang, Kai; Chandramouli, Gadisetti V.R. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Knott, Jason G. [Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University (United States); Leach, Richard, E-mail: Richard.leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group (United States)

    2013-07-12

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.

  20. Trophoblast lineage cells derived from human induced pluripotent stem cells

    International Nuclear Information System (INIS)

    Chen, Ying; Wang, Kai; Chandramouli, Gadisetti V.R.; Knott, Jason G.; Leach, Richard

    2013-01-01

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro

  1. Dedifferentiated chondrosarcoma of the larynx: Radiological, gross, microscopic and clinical features.

    Science.gov (United States)

    Magliocca, Kelly R; Edgar, Mark A; Corey, Amanda; Villari, Craig R

    2017-10-01

    Laryngeal chondrosarcoma is an uncommon malignancy with a predilection for the cricoid cartilage of adult male patients. Although rare, identification of aggressive chondrosarcoma variants, such as dedifferentiated chondrosarcoma (DDCS) may influence preoperative patient counseling, definitive surgical management, potential implementation of post-operative adjuvant therapy and prognosis. Herein we describe clinical and imaging features of laryngeal DDCS, the unique perspective of fresh and formalin fixed macroscopic examination, a spectrum of histopathologic findings, and detail the full course of the patient's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. 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.

  3. Chondrosarcoma of T2 Vertebrae Treated by Combined Anterior and Posterior Approach: A Case Report

    Directory of Open Access Journals (Sweden)

    K Norazian

    2010-11-01

    Full Text Available Chondrosarcoma of the spine is rare; it presents predominantly in very young males and presentation with neurological deficit is uncommon. Treatment of this type of tumour is mainly through surgery as adjuvant therapy is ineffective. En bloc resection of tumours in the spine are difficult although it remains the recommended treatment for chondrosarcoma. We report here presentation of a female with paresis (Frankel C whom was diagnosed with a large chondrosarcoma of the T2 vertebra extending to the right upper thoracic cavity. The patient underwent radical excision through an anterior and posterior approach to the spine.

  4. Case report 347: Dedifferentiated chondrosarcoma: Grade 4 fibrosarcoma arising in grade 1 chandrosarcoma (femur)

    International Nuclear Information System (INIS)

    Frassica, F.J.; Unni, K.K.; Sim, F.H.

    1986-01-01

    In summary, a 74-year-old woman presented with a 2-week history of pain in the left thigh. Dedifferentiated lesions have a very poor prognosis - less than 10% 5-year survivals. This figure contrasts with the 5-year survival rate of 59% for individuals with conventional chondrosarcoma. Fibrosarcoma is less common than osteosarcoma as the highly malignant, anaplastic portion of a dedifferentiated chondrosarcoma. In an unpublished series of 79 cases of dedifferentiated chondrosarcoma from the Mayo Clinic 43 showed osteosarcoma and 33 fibrosarcoma (Table 3). (orig.)

  5. Chondrosarcoma of bone complicating Ollier's disease: Report of a favourable response to radiotherapy

    International Nuclear Information System (INIS)

    Le, A.; Ball, D.; Pitman, A.; Fox, R.; King, K.

    2003-01-01

    Because chondrosarcoma of bone is traditionally thought to be a radioresistant malignancy, it is usually managed surgically. We report a case of multifocal chondrosarcoma arising in Ollier's disease for which the patient declined surgery. He was given a course of radical radiotherapy that resulted in symptom palliation and a radiologically confirmed remission that not only palliated his symptoms but also enabled him to achieve his goal of pursuing his profession before he died, 16 months later of multifocal sarcomatous transformation and metastatic disease. It is concluded that in patients with inoperable chondrosarcoma, radiotherapy can provide palliative benefit. Copyright (2003) Blackwell Science Pty Ltd

  6. Diffusion inside living human cells

    DEFF Research Database (Denmark)

    Leijnse, N.; Jeon, J. -H.; Loft, Steffen

    2012-01-01

    of the cell or within the nucleus. Also, granules in cells which are stressed by intense laser illumination or which have attached to a surface for a long period of time move in a more restricted fashion than those within healthy cells. For granules diffusing in healthy cells, in regions away from the cell...... cells. For these cells the exact diffusional pattern of a particular granule depends on the physiological state of the cell and on the localization of the granule within the cytoplasm. Granules located close to the actin rich periphery of the cell move less than those located towards to the center...

  7. Molecular regulation of human hematopoietic stem cells

    NARCIS (Netherlands)

    van Galen, P.L.J.

    2014-01-01

    Peter van Galen focuses on understanding the determinants that maintain the stem cell state. Using human hematopoietic stem cells (HSCs) as a model, processes that govern self-renewal and tissue regeneration were investigated. Specifically, a role for microRNAs in balancing the human HSC

  8. Recurrence of Pelvic Chondrosarcoma through Fascial Defect into Abdominal Cavity

    Directory of Open Access Journals (Sweden)

    Kemal Gökkuş

    2014-01-01

    Full Text Available Our patient was a 76-year-old female who has been operated on 2 times in 8 years for pelvic chondrosarcoma. The patient came to our clinic with a large mass in left iliac region which extended into the paravertebral area. Physical examination and preoperative imagining studies revealed a mass at the left iliac area that infiltrated sciatic notch and extended from posterior iliac region towards the anterior side of iliac bone through the sciatic notch and an incisional hernia including descending colon. The mass was also penetrating the abdominal cavity through the hernia. Surgical intervention was planned. Since the tumor infiltrated the sciatic nerve, hemipelvectomy was indicated. Patient refused hemipelvectomy. Therefore, palliative debulking surgery was considered. We treated the case with marginal excision and abdominal wall reconstruction employing prolene and vicryl suture materials in order to prevent a postoperative visceral herniation and local invasion. At the latest follow-up appointment in 2 years, the patient still had no signs of tumor recurrence. This case showed us that an incisional hernia can serve as a pathway for the recurrence invasion of the chondrosarcoma.

  9. Dedifferentiated chondrosarcoma of the appendicular skeleton: MRI-pathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    MacSweeney, Fergus; Darby, Alan [Department of Histopathology, The Royal National Orthopaedic Hospital NHS Trust, Brockley Hill, HA7 4LP, Stanmore, Middlesex (United Kingdom); The London Bone and Soft Tissue Tumour Unit, London (United Kingdom); Saifuddin, Asif [The London Bone and Soft Tissue Tumour Unit, London (United Kingdom); Department of Radiology, The Royal National Orthopaedic Hospital NHS Trust, Brockley Hill, HA7 4LP, Stanmore, Middlesex (United Kingdom); Department of Diagnostic Imaging, The Royal National Orthopaedic Hospital NHS Trust, HA7 4LP, Stanmore, Middlesex (United Kingdom)

    2003-12-01

    To correlate the T2-weighted and STIR MRI appearances of dedifferentiated appendicular chondrosarcoma with gross and microscopic pathology. Nine patients with a histologically confirmed diagnosis of dedifferentiated appendicular chondrosarcoma were identified from the Bone Tumour Registry. All patients underwent MRI, including T2-weighted and/or STIR sequences in at least one plane, prior to limb salvage surgery. Areas of reduced signal intensity (SI) compared with hyperintense chondral tumour on the T2-weighted or STIR images were correlated with the resection specimen, to determine the relationship of such out areas of reduced SI with regions of dedifferentiation. Patients presented over a period of 7 years. There were five men and four women with mean age 68.2 years and age range 51-78 years. Tumours arose in the femur (6 cases), humerus (2 cases) and tibia (1 case). Three MRI patterns were identified: (1) type 1, a lesion with two distinct signal characteristics - hyperintense chondral and reduced SI dedifferentiated tumour (n=6); type 2, mainly reduced SI lesion - dedifferentiated tumour, with areas of signal void corresponding to matrix calcification (n=2); type 3, a heterogeneous lesion with no radiological evidence of underlying chondral tumour (n=1). T2-weighted or STIR MR sequences can identify areas of dedifferentiation, which should be the preferential site of pre-operative biopsy. (orig.)

  10. Mesenchymal chondrosarcoma of the sacrum: a case report and review of the literature.

    Science.gov (United States)

    Biagini, R; Orsini, U; Demitri, S; Ruggieri, P; Ferrari, S; Bertoni, F

    2000-01-01

    The authors present a case of mesenchymal chondrosarcoma located in the sacrum of a 23-year-old patient treated with radiotherapy and chemotherapy. A review of the literature on the topic is also reported.

  11. Intraosseous Atypical Chondroid Tumor or Chondrosarcoma Grade 1 in Patients with Multiple Osteochondromas

    NARCIS (Netherlands)

    Goud, Annemarie L.; Wuyts, Wim; Bessems, Johannes; Bramer, Jos; van der Woude, Henk Jan; Ham, John

    2015-01-01

    Background: The autosomal dominant condition multiple osteochondromas, formerly called multiple hereditary exostoses, is associated with a risk of malignant progression of osteochondroma into secondary peripheral chondrosarcoma. Most patients with multiple osteochondromas have exostosin-1 or

  12. Dedifferentiated chondrosarcoma in patients with multiple osteochondromatosis: report of a case and review of the literature

    International Nuclear Information System (INIS)

    Kilpatrick, S.E.; Pike, E.J.; Ward, W.G.; Pope, T.L.

    1997-01-01

    Multiple osteochondromatosis (MOS) is a familial disorder of autosomal dominant transmission characterized by the development of multiple exostoses and often derangements of epiphyseal cartilage, sometimes resulting in long bone growth retardation. Patients with the disorder appear to be at increased risk for developing secondary chondrosarcomas. Rarely, dedifferentiated chondrosarcomas may also occur. We report a single case of a 27-year-old man with multiple osteochondromatosis who developed a fatal dedifferentiated chondrosarcoma. Radiographically, the neoplasm arose from the pelvis completely destroying the left pubic ramus. Subsequently, the patient underwent preoperative chemotherapy followed by a left external hemipelvectomy. On pathologic examination, the tumor was characterized by high-grade pleomorphic sarcoma sharply juxtaposed to a low-grade chondrosarcoma. The patient ultimately died of widespread metastatic sarcoma. (orig.). With 7 figs

  13. Dedifferentiated chondrosarcoma in patients with multiple osteochondromatosis: report of a case and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Kilpatrick, S.E. [Department of Pathology, North Carolina Baptist Hospitals, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (United States); Pike, E.J. [Department of Radiology, North Carolina Baptist Hospitals, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (United States); Ward, W.G. [Department of Orthopaedics, North Carolina Baptist Hospitals, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (United States); Pope, T.L. [Department of Radiology, North Carolina Baptist Hospitals, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (United States)

    1997-06-01

    Multiple osteochondromatosis (MOS) is a familial disorder of autosomal dominant transmission characterized by the development of multiple exostoses and often derangements of epiphyseal cartilage, sometimes resulting in long bone growth retardation. Patients with the disorder appear to be at increased risk for developing secondary chondrosarcomas. Rarely, dedifferentiated chondrosarcomas may also occur. We report a single case of a 27-year-old man with multiple osteochondromatosis who developed a fatal dedifferentiated chondrosarcoma. Radiographically, the neoplasm arose from the pelvis completely destroying the left pubic ramus. Subsequently, the patient underwent preoperative chemotherapy followed by a left external hemipelvectomy. On pathologic examination, the tumor was characterized by high-grade pleomorphic sarcoma sharply juxtaposed to a low-grade chondrosarcoma. The patient ultimately died of widespread metastatic sarcoma. (orig.). With 7 figs.

  14. Human monoclonal antibodies reactive with human myelomonocytic leukemia cells.

    Science.gov (United States)

    Posner, M R; Santos, D J; Elboim, H S; Tumber, M B; Frackelton, A R

    1989-04-01

    Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG1), HL 2.1 (IgG3), and HL 3.1 (IgG1) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000-54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen.

  15. Human hematopoietic cell culture, transduction, and analyses

    DEFF Research Database (Denmark)

    Bonde, Jesper; Wirthlin, Louisa; Kohn, Donald B

    2008-01-01

    This unit provides methods for introducing genes into human hematopoietic progenitor cells. The Basic Protocol describes isolation of CD34(+) cells, transduction of these cells with a retroviral vector on fibronectin-coated plates, assaying the efficiency of transduction, and establishing long-te...

  16. The lifetime of hypoxic human tumor cells

    International Nuclear Information System (INIS)

    Durand, Ralph E.; Sham, Edward

    1998-01-01

    Purpose: For hypoxic and anoxic cells in solid tumors to be a therapeutic problem, they must live long enough to be therapeutically relevant, or else be rapidly recruited into the proliferating compartment during therapy. We have, therefore, estimated lifetime and recruitment rate of hypoxic human tumor cells in multicell spheroids in vitro, or in xenografted tumors in SCID mice. Materials and Methods: Cell turnover was followed by flow cytometry techniques, using antibodies directed at incorporated halogenated pyrimidines. The disappearance of labeled cells was quantified, and verified to be cell loss rather than label dilution. Repopulation was studied in SiHa tumor xenografts during twice-daily 2.5-Gy radiation exposures. Results: The longevity of hypoxic human tumor cells in spheroids or xenografts exceeded that of rodent cell lines, and cell turnover was slower in xenografts than under static growth as spheroids. Human tumor cells remained viable in the hypoxic regions of xenografts for 4-10 days, compared to 3-5 days in spheroids, and 1-3 days for most rodent cells in spheroids. Repopulation was observed within the first few radiation treatments for the SiHa xenografts and, with accumulated doses of more than 10 Gy, virtually all recovered cells had progressed through at least one S-phase. Conclusion: Our results suggest an important difference in the ability of human vs. rodent tumor cells to withstand hypoxia, and raise questions concerning the increased longevity seen in vivo relative to the steady-state spheroid system

  17. Enchondroma vs. chondrosarcoma: A simple, easy-to-use, new magnetic resonance sign

    International Nuclear Information System (INIS)

    Vanel, Daniel; Kreshak, Jennifer; Larousserie, Frédérique; Alberghini, Marco; Mirra, Joe; De Paolis, Massimiliano; Picci, Piero

    2013-01-01

    Introduction: There is no clear radiologic or pathologic agreement on the differences between enchondroma and conventional chondrosarcoma, which has huge therapeutic consequences. Microscopically, an enchondroma is composed of “islands of intramedullary hyaline cartilage surrounded by marrow fat”, and a chondrosarcoma a “diffuse cartilaginous replacement (invasion) of the marrow which leads to complete ‘trapping’ of host lamellar bone trabeculae.” The marrow around islands of cartilage should be detectable on magnetic resonance imaging (MR). Enchondroma may be the precursor of chondrosarcoma; benign cartilaginous islands are often seen microscopically at the periphery of chondrosarcoma. We attempted to detect these islands at the periphery of chondrosarcomas on MR and correlate them microscopically. Materials and methods: We examined our database for all patients with a chondrosarcoma of the long and flat bones between 1990 and 2007. Only those with a preoperative MR who underwent an en bloc resection were included, yielding 32 patients. We looked for low-signal islands surrounded by high (fat) signal on T1-weighted images, and high-signal islands surrounded by low signal on T2-weighted fat saturated images at the periphery of the main tumour mass. Microscopic correlation was performed in all cases. Results: On microscopy, there were 23 conventional chondrosarcomas, nine dedifferentiated. Peripheral islands surrounded by fat were detected on MR in 19 cases, corresponding to benign cartilage in 18 cases and to the benign scar of a needle biopsy tract in one. There were no peripheral islands detected radiographically or microscopically in 13 cases. Conclusion: Cartilaginous islands microscopically detected at the periphery of some chondrosarcomas are easily and reliably diagnosed on MR

  18. Enchondroma vs. chondrosarcoma: A simple, easy-to-use, new magnetic resonance sign

    Energy Technology Data Exchange (ETDEWEB)

    Vanel, Daniel, E-mail: daniel.vanel@ior.it [Department of Research, Istituto Ortopedico Rizzoli, Bologna (Italy); Department of Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy); Kreshak, Jennifer [Department of Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy); Department of Orthopaedic Oncology, Istituto Ortopedico Rizzoli, Bologna (Italy); Larousserie, Frédérique [Department of Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy); Université Paris Descartes, Sorbonne Paris Cité, Paris (France); Alberghini, Marco; Mirra, Joe [Department of Pathology, Istituto Ortopedico Rizzoli, Bologna (Italy); De Paolis, Massimiliano [Department of Orthopaedic Oncology, Istituto Ortopedico Rizzoli, Bologna (Italy); Picci, Piero [Department of Research, Istituto Ortopedico Rizzoli, Bologna (Italy)

    2013-12-01

    Introduction: There is no clear radiologic or pathologic agreement on the differences between enchondroma and conventional chondrosarcoma, which has huge therapeutic consequences. Microscopically, an enchondroma is composed of “islands of intramedullary hyaline cartilage surrounded by marrow fat”, and a chondrosarcoma a “diffuse cartilaginous replacement (invasion) of the marrow which leads to complete ‘trapping’ of host lamellar bone trabeculae.” The marrow around islands of cartilage should be detectable on magnetic resonance imaging (MR). Enchondroma may be the precursor of chondrosarcoma; benign cartilaginous islands are often seen microscopically at the periphery of chondrosarcoma. We attempted to detect these islands at the periphery of chondrosarcomas on MR and correlate them microscopically. Materials and methods: We examined our database for all patients with a chondrosarcoma of the long and flat bones between 1990 and 2007. Only those with a preoperative MR who underwent an en bloc resection were included, yielding 32 patients. We looked for low-signal islands surrounded by high (fat) signal on T1-weighted images, and high-signal islands surrounded by low signal on T2-weighted fat saturated images at the periphery of the main tumour mass. Microscopic correlation was performed in all cases. Results: On microscopy, there were 23 conventional chondrosarcomas, nine dedifferentiated. Peripheral islands surrounded by fat were detected on MR in 19 cases, corresponding to benign cartilage in 18 cases and to the benign scar of a needle biopsy tract in one. There were no peripheral islands detected radiographically or microscopically in 13 cases. Conclusion: Cartilaginous islands microscopically detected at the periphery of some chondrosarcomas are easily and reliably diagnosed on MR.

  19. Spinal chondrosarcoma demonstrated by Tc-99m-MDP bone scan

    International Nuclear Information System (INIS)

    Smith, F.W.; Nandi, S.C.; Mills, K.

    1982-01-01

    A case of chondrosarcoma of the spine in a 45-year-old woman is described. The bone scan performed after the intravenous injection of Tc-99m-MDP not only confirmed the solitary nature of the tumor, but also demonstrated its extent within the spinous process of the second dorsal vertebra. Preoperative bone scan in the management of chondrosarcoma is advocated as a safe, noninvasive technique for assessing the extent of the tumor

  20. MR features of multiple enchondromas with associated chondrosarcoma in the lower extremities

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Kyung Yoon; Sung, Mi Sook; Lee, Hee Jeong; Park, Il Joong; Lee, Jae Young; Yu, Won Jong; Lee, Gook Jin; Jeon, Sang Hoon; Yu, Mi Na; Yoon, Se Cheol [College of Medicine, The Catholic University of Korea, Bucheon St. Mary' s Hospital, Bucheon (Korea, Republic of)

    2016-02-15

    Multiple enchondromas are well described in the literature, however, the associated spectrum of MR imaging findings remains unclear. Secondary chondrosarcoma of the hand and feet associated with multiple enchondromas is extremely rare. Herein, we reported a case of multiple enchondromas of intramedullary, intracortical, and periosteal location with associated low-grade chondrosarcomas in the lower extremities on MR imaging in a 57 year old woman.

  1. Outcomes of curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma of long bone.

    Science.gov (United States)

    Kim, Wanlim; Han, Ilkyu; Kim, Eo Jin; Kang, Seungcheol; Kim, Han-Soo

    2015-06-01

    Low-grade chondrosarcoma of long bones can be treated successfully with extended intralesional curettage using adjuvants. However, there is no study reporting the use of anhydrous alcohol as an adjuvant in the treatment of low-grade chondrosarcoma. We asked (1) whether intralesional curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma is associated with good oncologic outcomes; and we report (2) the complications of the procedure. Thirty-six patients (13 men, 23 women) with a mean age of 46 years (range, 18-67 years) were treated for low-grade chondrosarcoma and followed up for a median of 62 months (range, 24-169 months). After intralesional curettage, and additional burring, anhydrous alcohol was used as an adjuvant therapy. At the time of last follow-up, there were no local recurrences or distant metastases. Six patients developed complications: 4 postoperative fractures (11%), 1 intra-articular loose body (3%) and 1 postoperative joint stiffness (3%). Anhydrous alcohol is a reasonable adjuvant for the curettage of low-grade chondrosarcoma of long bones. A long-term follow-up study is necessary, considering the slow biological progression of low-grade chondrosarcoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. CASE REPORT:Chondrosarcoma of Rib on Fine Needle Aspiration Cytology – A Rare Site

    Directory of Open Access Journals (Sweden)

    Prakash M Patil

    2012-07-01

    Full Text Available Background: Fine needle aspiration cytology (FNAC is effective in the diagnosis of bone tumors when combined with careful radiologic and clinical evaluation. Chondrosarcomas often arise in the pelvis or bones of the trunk, but primary chest wall (rib chondrosarcomas are relatively rare. Case Reports: This is a case of a patient with a chondrosarcoma arising in the left lower rib who underwent resection. The patient was a 30-year-old man with a 10x8x6cm tumor in the anterior chest wall of the left side lower rib. On Fine Needle Aspiration Cytology (FNAC of the mass on the anterior chest wall, a diagnosis of a low grade chondrosarcoma was made. This was confirmed histopathologically as a dedifferentiated chondrosarcoma. Macroscopically on excision of gray to pink lobulated mass with adjacent soft tissue and bone with foci of hemorrhage and necrosis the mass measured (M 10x 8x 6 cm. Incidence of chondrosarcoma peaks in the 5th to 6th decade and most commonly involves the femur, humerus, pelvis, and scapula. It rarely involves rib.

  3. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    NARCIS (Netherlands)

    Guadix, Juan Antonio; Orlova, Valeria V.; Giacomelli, Elisa; Bellin, Milena; Ribeiro, Marcelo C.; Mummery, Christine L.; Pérez-Pomares, José M.; Passier, Robert

    2017-01-01

    Human pluripotent stem cells (hPSCs) are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced) to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA)

  4. Diagnostic utility of IDH1/2 mutations to distinguish dedifferentiated chondrosarcoma from undifferentiated pleomorphic sarcoma of bone.

    Science.gov (United States)

    Chen, Shaoxiong; Fritchie, Karen; Wei, Shi; Ali, Naser; Curless, Kendra; Shen, Tiansheng; Brini, Anna T; Latif, Farida; Sumathi, Vaiyapuri; Siegal, Gene P; Cheng, Liang

    2017-07-01

    Histologically, it is nearly impossible to distinguish the dedifferentiated component of dedifferentiated chondrosarcoma from undifferentiated pleomorphic sarcoma (UPS) of bone when the low-grade cartilaginous component is absent. Previous studies have revealed that isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are present in a significant number of cartilaginous tumors including most conventional chondrosarcomas and dedifferentiated chondrosarcomas. These mutations have not been studied in UPSs of bone. We sought to investigate whether an IDH1 or IDH2 mutation signature could be used as a clinically diagnostic marker for the distinction of dedifferentiated component of chondrosarcoma from UPS of bone. Sixty-eight bone tumor cases, including 31 conventional chondrosarcomas, 23 dedifferentiated chondrosarcomas, and 14 UPSs of bone, were collected for IDH1/2 mutation analysis either using the Qiagen IDH1/2 RGQ PCR Kit or using whole-exome sequencing. IDH1/2 mutations were detected in 87% (20/23) of dedifferentiated chondrosarcomas and 30% (6/20) of conventional chondrosarcomas. No mutations were detected in the IDH1/2 codon 132 or codon 172 among 14 UPSs of bone. Identification of IDH1 or IDH2 mutations supports the diagnosis of dedifferentiated chondrosarcoma rather than UPS of bone while also providing some insight into the pathogenesis of these 2 lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Radiation effects on cultured human lymphoid cells

    International Nuclear Information System (INIS)

    Johansson, L.; Nilsson, K.; Carlsson, J.; Larsson, B.; Jakobsson, P.

    1981-01-01

    The cloning efficiency of human normal and malignant lymphoid cells is usually low. Radiation effects in vitro on such cells can therefore not be analysed with conventional cloning. However, this problem can be circumscribed by using the growth extrapolation method. A panel of human leukemia-lymphoma cell-lines representing Epstein-Barr virus carrying lymphoblastoid cells of presumed non-neoplastic derivation and neoplastic T- and B-lymphocytes was used to test the efficiency of this method. The sensitivity to radiation could be determined for all these cell types. The growth extrapolation method gave generally the same result as conventional cloning demonstrated by comparison with one exceptional cell-line with capacity for cloning in agar. The sensitivity varied largely between the different cell types. A common feature was that none of the cell lines had a good capacity to accumulate sublethal radiation injury. (Auth.)

  6. Energy Generation in the Human Body by the Human Cells ...

    African Journals Online (AJOL)

    We adapted the thermodynamics equation for energy generation in a diesel engine in modeling energy generation in human body by the human cells by doing a thorough study on both systems and saw that the process of energy generation is the same in them. We equally saw that the stages involved in energy generation ...

  7. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    Science.gov (United States)

    Barkla, D H; Whitehead, R H; Foster, H; Tutton, P J

    1988-09-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting from the apical surface. The microvilli are attached by a core of long microfilaments passing deep into the apical cytoplasm. Between the microvilli are parallel arrays of vesicles (caveoli) containing flocculent material. Two different but not mutually exclusive explanations for the presence of tuft cells are proposed. The first explanation is that tuft cells came from the resected tumour and have survived by mitotic division during subsequent passages. The second explanation suggests that tuft cells are the progeny of undifferentiated tumour cells. Descriptions of tuft cells in colon carcinomas are uncommon and possible reasons for this are presented. The morphology of tuft cells is consistent with that of a highly differentiated cell specialised for absorption, and these new models provide an opportunity to further investigate the structure and function of tuft cells.

  8. Sensing radiosensitivity of human epidermal stem cells

    International Nuclear Information System (INIS)

    Rachidi, Walid; Harfourche, Ghida; Lemaitre, Gilles; Amiot, Franck; Vaigot, Pierre; Martin, Michele T.

    2007-01-01

    Purpose: Radiosensitivity of stem cells is a matter of debate. For mouse somatic stem cells, both radiosensitive and radioresistant stem cells have been described. By contrast, the response of human stem cells to radiation has been poorly studied. As epidermis is a radiosensitive tissue, we evaluated in the present work the radiosensitivity of cell populations enriched for epithelial stem cells of human epidermis. Methods and materials: The total keratinocyte population was enzymatically isolated from normal human skin. We used flow cytometry and antibodies against cell surface markers to isolate basal cell populations from human foreskin. Cell survival was measured after a dose of 2 Gy with the XTT assay at 72 h after exposure and with a clonogenic assay at 2 weeks. Transcriptome analysis using oligonucleotide microarrays was performed to assess the genomic cell responses to radiation. Results: Cell sorting based on two membrane proteins, α6 integrin and the transferrin receptor CD71, allowed isolation of keratinocyte populations enriched for the two types of cells found in the basal layer of epidermis: stem cells and progenitors. Both the XTT assay and the clonogenic assay showed that the stem cells were radioresistant whereas the progenitors were radiosensitive. We made the hypothesis that upstream DNA damage signalling might be different in the stem cells and used microarray technology to test this hypothesis. The stem cells exhibited a much more reduced gene response to a dose of 2 Gy than the progenitors, as we found that 6% of the spotted genes were regulated in the stem cells and 20% in the progenitors. Using Ingenuity Pathway Analysis software, we found that radiation exposure induced very specific pathways in the stem cells. The most striking responses were the repression of a network of genes involved in apoptosis and the induction of a network of cytokines and growth factors. Conclusion: These results show for the first time that keratinocyte

  9. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Juan Antonio Guadix

    2017-12-01

    Full Text Available Summary: Human pluripotent stem cells (hPSCs are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA and bone morphogenetic protein 4 (BMP4 promoted expression of the mesodermal marker PDGFRα, upregulated characteristic (proepicardial progenitor cell genes, and downregulated transcription of myocardial genes. We confirmed the (proepicardial-like properties of these cells using in vitro co-culture assays and in ovo grafting of hPSC-epicardial cells into chick embryos. Our data show that RA + BMP4-treated hPSCs differentiate into (proepicardial-like cells displaying functional properties (adhesion and spreading over the myocardium of their in vivo counterpart. The results extend evidence that hPSCs are an excellent model to study (proepicardial differentiation into cardiovascular cells in human development and evaluate their potential for cardiac regeneration. : The authors have shown that hPSCs can be instructed in vitro to differentiate into a specific cardiac embryonic progenitor cell population called the proepicardium. Proepicardial cells are required for normal formation of the heart during development and might contribute to the development of cell-based therapies for heart repair. Keywords: human pluripotent stem cells, proepicardium, progenitor cells, cardiovascular, differentiation

  10. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Varga, Nora [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Vereb, Zoltan; Rajnavoelgyi, Eva [Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen (Hungary); Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Apati, Agota, E-mail: apati@kkk.org.hu [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  11. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    International Nuclear Information System (INIS)

    Varga, Nóra; Veréb, Zoltán; Rajnavölgyi, Éva; Német, Katalin; Uher, Ferenc; Sarkadi, Balázs; Apáti, Ágota

    2011-01-01

    Highlights: ► MSC like cells were derived from hESC by a simple and reproducible method. ► Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. ► MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  12. Toxicity of diuron in human cancer cells.

    Science.gov (United States)

    Huovinen, Marjo; Loikkanen, Jarkko; Naarala, Jonne; Vähäkangas, Kirsi

    2015-10-01

    Diuron is a substituted phenylurea used as a herbicide to control broadleaf and grass weeds and as a biocidal antifouling agent. Diuron is carcinogenic in rat urinary bladder and toxic to the reproductive system of oysters, sea urchins and lizards. The few studies carried out in human cells do not include the genotoxicity of diuron. We have investigated the toxicity of diuron in human breast adenocarcinoma (MCF-7) and human placental choriocarcinoma (BeWo) cells. The production of reactive oxygen species (ROS) was statistically significantly increased in both cell lines but only at the highest 200 μM concentration. Diuron clearly reduced the viability of BeWo, but not MCF-7 cells. The relative cell number was decreased in both cell lines indicative of inhibition of cell proliferation. In the Comet assay, diuron increased DNA fragmentation in MCF-7 but not in BeWo cells. The expressions of p53 protein, a marker for cell stress, and p21 protein, a transcriptional target of p53, were increased, but only in MCF-7 cells. In conclusion, our results suggest that diuron is cytotoxic and potentially genotoxic in a tissue-specific manner and that ROS play a role in its toxicity. Thus, exposure to diuron may exert harmful effects on fetal development and damage human health. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng

    2012-01-01

    Full Text Available Multiple layers of suppressive components including regulatory T (TReg cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TReg cells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TReg cells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TReg cells in preclinical and clinical settings.

  14. Genome Editing in Human Pluripotent Stem Cells.

    Science.gov (United States)

    Carlson-Stevermer, Jared; Saha, Krishanu

    2017-01-01

    Genome editing in human pluripotent stem cells (hPSCs) enables the generation of reporter lines and knockout cell lines. Zinc finger nucleases, transcription activator-like effector nucleases (TALENs), and CRISPR/Cas9 technology have recently increased the efficiency of proper gene editing by creating double strand breaks (DSB) at defined sequences in the human genome. These systems typically use plasmids to transiently transcribe nucleases within the cell. Here, we describe the process for preparing hPSCs for transient expression of nucleases via electroporation and subsequent analysis to create genetically modified stem cell lines.

  15. Modeling human infertility with pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Di Chen

    2017-05-01

    Full Text Available Human fertility is dependent upon the correct establishment and differentiation of the germline. This is because no other cell type in the body is capable of passing a genome and epigenome from parent to child. Terminally differentiated germline cells in the adult testis and ovary are called gametes. However, the initial specification of germline cells occurs in the embryo around the time of gastrulation. Most of our knowledge regarding the cell and molecular events that govern human germline specification involves extrapolating scientific principles from model organisms, most notably the mouse. However, recent work using next generation sequencing, gene editing and differentiation of germline cells from pluripotent stem cells has revealed that the core molecular mechanisms that regulate human germline development are different from rodents. Here, we will discuss the major molecular pathways required for human germline differentiation and how pluripotent stem cells have revolutionized our ability to study the earliest steps in human embryonic lineage specification in order to understand human fertility.

  16. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2008-01-01

    Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired

  17. Guidelines for human embryonic stem cell research

    National Research Council Canada - National Science Library

    Committee on Guidelines for Human Embryonic Stem Cell Research, National Research Council

    2005-01-01

    Since 1998, the volume of research being conducted using human embryonic stem (hES) cells has expanded primarily using private funds because of restrictions on the use of federal funds for such research...

  18. Satellite cells in human skeletal muscle plasticity

    Directory of Open Access Journals (Sweden)

    Tim eSnijders

    2015-10-01

    Full Text Available Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodelling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodelling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodelling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  19. Human stem cells for craniomaxillofacial reconstruction.

    Science.gov (United States)

    Jalali, Morteza; Kirkpatrick, William Niall Alexander; Cameron, Malcolm Gregor; Pauklin, Siim; Vallier, Ludovic

    2014-07-01

    Human stem cell research represents an exceptional opportunity for regenerative medicine and the surgical reconstruction of the craniomaxillofacial complex. The correct architecture and function of the vastly diverse tissues of this important anatomical region are critical for life supportive processes, the delivery of senses, social interaction, and aesthetics. Craniomaxillofacial tissue loss is commonly associated with inflammatory responses of the surrounding tissue, significant scarring, disfigurement, and psychological sequelae as an inevitable consequence. The in vitro production of fully functional cells for skin, muscle, cartilage, bone, and neurovascular tissue formation from human stem cells, may one day provide novel materials for the reconstructive surgeon operating on patients with both hard and soft tissue deficit due to cancer, congenital disease, or trauma. However, the clinical translation of human stem cell technology, including the application of human pluripotent stem cells (hPSCs) in novel regenerative therapies, faces several hurdles that must be solved to permit safe and effective use in patients. The basic biology of hPSCs remains to be fully elucidated and concerns of tumorigenicity need to be addressed, prior to the development of cell transplantation treatments. Furthermore, functional comparison of in vitro generated tissue to their in vivo counterparts will be necessary for confirmation of maturity and suitability for application in reconstructive surgery. Here, we provide an overview of human stem cells in disease modeling, drug screening, and therapeutics, while also discussing the application of regenerative medicine for craniomaxillofacial tissue deficit and surgical reconstruction.

  20. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  1. HLA engineering of human pluripotent stem cells.

    Science.gov (United States)

    Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

    2013-06-01

    The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I-negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8(+) T cell responses were reduced in class I-negative cells that had undergone differentiation in embryoid bodies. These B2M(-/-) ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines.

  2. HLA Engineering of Human Pluripotent Stem Cells

    Science.gov (United States)

    Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

    2013-01-01

    The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I–negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8+ T cell responses were reduced in class I–negative cells that had undergone differentiation in embryoid bodies. These B2M−/− ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines. PMID:23629003

  3. DNA fork displacement rates in human cells

    International Nuclear Information System (INIS)

    Kapp, L.N.; Painter, R.B.

    1981-01-01

    DNA fork displacement rates were measured in 20 human cell lines by a bromodeoxyuridine-313 nm photolysis technique. Cell lines included representatives of normal diploid, Fanconi's anemia, ataxia telangiectasia, xeroderma pigmentosum, trisomy-21 and several transformed lines. The average value for all the cell lines was 0.53 +- 0.08 μm/min. The average value for individual cell lines, however, displayed a 30% variation. Less than 10% of variation in the fork displacement rate appears to be due to the experimental technique; the remainder is probably due to true variation among the cell types and to culture conditions. (Auth.)

  4. DNA fork displacement rates in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Kapp, L.N.; Painter, R.B. (California Univ., San Francisco (USA). Lab. of Radiobiology)

    1981-11-27

    DNA fork displacement rates were measured in 20 human cell lines by a bromodeoxyuridine-313 nm photolysis technique. Cell lines included representatives of normal diploid, Fanconi's anemia, ataxia telangiectasia, xeroderma pigmentosum, trisomy-21 and several transformed lines. The average value for all the cell lines was 0.53 +- 0.08 ..mu..m/min. The average value for individual cell lines, however, displayed a 30% variation. Less than 10% of variation in the fork displacement rate appears to be due to the experimental technique; the remainder is probably due to true variation among the cell types and to culture conditions.

  5. Signaling hierarchy regulating human endothelial cell development

    Science.gov (United States)

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these stud...

  6. The biology of human innate lymphoid cells

    NARCIS (Netherlands)

    Bernink, J.H.J.

    2016-01-01

    In this thesis I performed studies to investigate the contribution of human innate lymphoid cells (ILCs) in maintaining the mucosal homeostasis, initiating and/or propagating inflammatory responses, but also - when not properly regulated - how these cells contribute to immunopathology. First I

  7. miR-181a Targets RGS16 to Promote Chondrosarcoma Growth, Angiogenesis, and Metastasis.

    Science.gov (United States)

    Sun, Xiaojuan; Charbonneau, Cherie; Wei, Lei; Chen, Qian; Terek, Richard M

    2015-09-01

    Chondrosarcoma is the most common primary malignant bone tumor in adults, has no effective systemic treatment, and patients with this disease have poor survival. Altered expression of microRNA (miR) is involved in tumorigenesis; however, its role in chondrosarcoma is undetermined. miR-181a is overexpressed in high-grade chondrosarcoma, is upregulated by hypoxia, and increases VEGF expression. Here, the purpose was to determine the mechanism of miR-181a regulation of VEGF, determine whether miR-181a overexpression promotes tumor progression, and to evaluate an antagomir-based approach for chondrosarcoma treatment. Therapeutic inhibition of miR-181a decreased expression of VEGF and MMP1 in vitro, and angiogenesis, MMP1 activity, tumor growth, and lung metastasis, all by more than 50%, in a xenograft mouse model. A target of miR-181a is a regulator of G-protein signaling 16 (RGS16), a negative regulator of CXC chemokine receptor 4 (CXCR4) signaling. CXCR4 signaling is increased in chondrosarcoma, its expression is also increased by hypoxia, and is associated with angiogenesis and metastasis; however, receptor blockade is only partially effective. RGS16 expression is restored after miR-181a inhibition and partially accounts for the antiangiogenic and antimetastatic effects of miR-181a inhibition. These data establish miR-181a as an oncomiR that promotes chondrosarcoma progression through a new mechanism involving enhancement of CXCR4 signaling by inhibition of RGS16. Targeting miR-181a can inhibit tumor angiogenesis, growth, and metastasis, thus suggesting the possibility of antagomir-based therapy in chondrosarcoma. ©2015 American Association for Cancer Research.

  8. Absence of IHH and retention of PTHrP signalling in enchondromas and central chondrosarcomas.

    Science.gov (United States)

    Rozeman, Leida B; Hameetman, Liesbeth; Cleton-Jansen, Anne-Marie; Taminiau, Anthonie H M; Hogendoorn, Pancras C W; Bovée, Judith V M G

    2005-03-01

    Enchondromas and conventional central chondrosarcomas are, respectively, benign and malignant hyaline cartilage-forming tumours that originate in the medulla of bone. In order to gain a better understanding of the molecular process underlying malignant transformation of enchondroma, and to investigate whether there is a biological difference between conventional central cartilaginous tumours and those of enchondromatosis or with phalangeal localization, a series of 64 enchondromas (phalanx, n = 21; enchondromatosis, n = 15) and 89 chondrosarcomas (phalanx, n = 17; enchondromatosis, n = 13) was collected. Indian Hedgehog (IHH)/parathyroid hormone related peptide (PTHrP) signalling, an important pathway in chondrocyte proliferation and differentiation within the normal growth plate, was studied by immunohistochemical analysis of the expression of PTHrP, PTHR1, Bcl-2, p21, cyclin D1, and cyclin E. Quantitative real-time PCR for IHH, PTCH, SMO, and GLI2 was performed on a subset of tumours. The data show that IHH signalling is absent in enchondromas and central chondrosarcomas, while PTHrP signalling is active. There was no difference in the expression of any of the molecules between 35 enchondromas and 26 grade I central chondrosarcomas, indicating that PTHrP signalling is not important in malignant transformation of enchondroma. Higher expression of PTHR1 and Bcl-2 was associated with increasing histological grade in chondrosarcoma, suggesting involvement in tumour progression. No difference was found between samples from enchondromatosis patients and solitary cases, suggesting no difference in PTHrP signalling. A small subset of phalangeal chondrosarcomas demonstrated down-regulation of PTHrP, which may be related to its more indolent clinical behaviour. Thus, in both enchondromas and central chondrosarcomas, PTHrP signalling is active and independent of IHH signalling, irrespective of the presence or absence of enchondromatosis.

  9. Haematopoietic stem and progenitor cells from human pluripotent stem cells

    Science.gov (United States)

    Sugimura, Ryohichi; Jha, Deepak Kumar; Han, Areum; Soria-Valles, Clara; da Rocha, Edroaldo Lummertz; Lu, Yi-Fen; Goettel, Jeremy A.; Serrao, Erik; Rowe, R. Grant; Malleshaiah, Mohan; Wong, Irene; Sousa, Patricia; Zhu, Ted N.; Ditadi, Andrea; Keller, Gordon; Engelman, Alan N.; Snapper, Scott B.; Doulatov, Sergei; Daley, George Q.

    2018-01-01

    A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders. PMID:28514439

  10. DNA repair in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Fornace, A.J. Jr.; Lechner, J.F.; Grafstrom, R.C.; Harris, C.C.

    1982-01-01

    The purpose of this investigation was to compare the response of human cell types (bronchial epithelial cells and fibroblasts and skin fibroblasts) to various DNA damaging agents. Repair of DNA single strand breaks (SSB) induced by 5 krads of X-ray was similar for all cell types; approximately 90% of the DNA SSB were rejoined within one hour. During excision repair of DNA damage from u.v.-radiation, the frequencies of DNA SSB as estimated by the alkaline elution technique, were similar in all cell types. Repair replication as measured by BND cellulose chromatography was also similar in epithelial and fibroblastic cells after u.v.-irradiation. Similar levels of SSB were also observed in epithelial and fibroblastic cells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene; benzo[a]pyrene diol epoxide (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine. Significant repair replication of BPDE-induced DNA damage was detected in both bronchial epithelial and fibroblastic cells, although the level in fibroblasts was approximately 40% of that in epithelial cells. The pulmonary carcinogen asbestos did not damage DNA. DNA-protein crosslinks induced by formaldehyde were rapidly removed in bronchial cells. Further, epithelial and fibroblastic cells, which were incubated with formaldehyde and the polymerase inhibitor combination of cytosine arabinoside and hydroxyurea, accumulated DNA SSB at approximately equal frequencies. These results should provide a useful background for further investigations of the response of human bronchial cells to various DNA damaging agents

  11. Interaction of Staphylococci with Human B cells.

    Directory of Open Access Journals (Sweden)

    Tyler K Nygaard

    Full Text Available Staphylococcus aureus is a leading cause of human infections worldwide. The pathogen produces numerous molecules that can interfere with recognition and binding by host innate immune cells, an initial step required for the ingestion and subsequent destruction of microbes by phagocytes. To better understand the interaction of this pathogen with human immune cells, we compared the association of S. aureus and S. epidermidis with leukocytes in human blood. We found that a significantly greater proportion of B cells associated with S. epidermidis relative to S. aureus. Complement components and complement receptors were important for the binding of B cells with S. epidermidis. Experiments using staphylococci inactivated by ultraviolet radiation and S. aureus isogenic deletion mutants indicated that S. aureus secretes molecules regulated by the SaeR/S two-component system that interfere with the ability of human B cells to bind this bacterium. We hypothesize that the relative inability of B cells to bind S. aureus contributes to the microbe's success as a human pathogen.

  12. Isolation of Human Innate Lymphoid Cells.

    Science.gov (United States)

    Krabbendam, Lisette; Nagasawa, Maho; Spits, Hergen; Bal, Suzanne M

    2018-06-29

    Innate lymphoid cells (ILCs) are innate immune cells of lymphoid origin that have important effector and regulatory functions in the first line of defense against pathogens, but also regulate tissue homeostasis, remodeling, and repair. Their function mirrors T helper cells and cytotoxic CD8 + T lymphocytes, but they lack expression of rearranged antigen-specific receptors. Distinct ILC subsets are classified in group 1 ILCs (ILC1s), group 2 ILCs (ILC2s), and group 3 ILCs (ILC3s and lymphoid tissue-inducer cells), based on the expression of transcription factors and the cytokines they produce. As the frequency of ILCs is low, their isolation requires extensive depletion of other cell types. The lack of unique cell surface antigens further complicates the identification of these cells. Here, methods for ILC isolation and characterization from human peripheral blood and different tissues are described. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

  13. The anabolic effects of insulin on type II collagen synthesis of Swarm rat chondrosarcoma chondrocytes

    International Nuclear Information System (INIS)

    Bembenek, M.E.; Liberti, J.P.

    1984-01-01

    The anabolic effects of insulin on collagen production of freshly isolated Swarm rat chondrosarcoma chondrocytes were investigated. The specific radioactivity of newly synthesized collagen was not increased by insulin, indicating that the hormone has no effect on the specific radioactivity of the aminoacyl tRNA pool. Results of further studies obtained from collagen degradation experiments demonstrated that insulin did not alter the rate of [3H]collagen degradation. Together, these results clearly indicate that insulin stimulates collagen biosynthesis. Polyacrylamide gel analysis of the newly synthesized collagen of both control and insulin-stimulated cells revealed a large-molecular-weight component which migrated with authentic alpha 1(II) collagen and was collagenase-sensitive. Additional studies showed that, although insulin increased the processing and secretion of collagen, the hormone did not cause a shift in the distribution of the extracellular and intracellular collagen pools. Finally, results of studies conducted with the transcriptional inhibitor, actinomycin D, indicated that the anabolic effects of insulin on collagen and non-collagen proteins were mediated at a post-transcriptional site

  14. Human CD56bright NK Cells

    DEFF Research Database (Denmark)

    Michel, Tatiana; Poli, Aurélie; Cuapio, Angelica

    2016-01-01

    Human NK cells can be subdivided into various subsets based on the relative expression of CD16 and CD56. In particular, CD56(bright)CD16(-/dim) NK cells are the focus of interest. They are considered efficient cytokine producers endowed with immunoregulatory properties, but they can also become c...... NK cell subsets is not fully defined, nor is their precise hematopoietic origin. In this article, we summarize recent studies about CD56(bright) NK cells in health and disease and briefly discuss the current controversies surrounding them....

  15. Immunohistochemical localization of steroid receptor coactivators in chondrosarcoma: an in vivo tissue microarray study.

    Science.gov (United States)

    Li, Wei; Fu, Jingshu; Bian, Chen; Zhang, Jiqiang; Xie, Zhao

    2014-12-01

    Chondrosarcoma is the second most common type of primary bone malignancy following up osteosarcoma, characterized by resistance to conventional chemotherapeutic agents and radiation regimens. The p160 family members steroid receptor coactivator-1 and -3 (SRC-1 and SRC-3) have been implied in the regulation of cancer growth, migration, invasion, metastasis and chemotherapeutic resistance; but we still lack detailed information about the levels of SRCs in chondrosarcoma. In this study, expression of SRC-1 and SRC-3 in chondrosarcoma was examined by immunohistochemistry with tissue microarrays; the four score system (0, 1, 2 and 3) was used to evaluate the staining. The results showed that there were no gender-, site- or age-differences regarding the expression of SRC-1 or SRC-3 (p>0.05); organ (bone or cartilage) -differences were only detected for SRC-1 but not SRC-3 (pchondrosarcoma, may be novel targets for the prognosis and/or treatment of chondrosarcoma, would have opened a new avenue and established foundation for studying chondrosarcoma. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. Temporo-mandibular joint chondrosarcoma: Case report and review of the literature.

    Science.gov (United States)

    Giorgione, C; Passali, F M; Varakliotis, T; Sibilia, M; Ottaviani, F

    2015-06-01

    Chondrosarcoma is a malignant mesenchymal tumour of cartilaginous origin. It represents 11% of all malignant primary bone tumours, and the pelvis, ribs, femur and humerus are most frequently involved. Chondrosarcoma of the head and neck region is a rare disease, and represents approximately 0.1% of all head and neck neoplasms. This report describes a rare localisation of chondrosarcoma in a 56-year-old man who presented with swelling in the right preauricular area and mild limitation and pain in the mouth opening. Since 1959, just a few cases of temporomandibular joint (TMJ) chondrosarcoma have been described. Computed tomography revealed a large mass (39 x 46 x 40 mm) in the right preauricular and parotid region with morpho-structural alterations of the condyle and an intense periostotic reaction. The tumour was treated by total parotidectomy and condylotomy. The VII cranial nerve was preserved. Histopathologic examination revealed a low grade chondrosarcoma with a 50% proliferation index. At present, the patient is still receiving routine follow-up after radiotherapy and physiotherapy.

  17. Dedifferentiated chondrosarcoma with leukocytosis and elevation of serum G-CSF. A case report

    Directory of Open Access Journals (Sweden)

    Oda Yoshinao

    2006-07-01

    Full Text Available Abstract Background G-CSF is known to function as a hematopoietic growth factor and it is known to be responsible for leukocytosis. G-CSF-producing tumors associated with leukocytosis include various types of malignancies. Case presentation We report the case of a 72-year-old man with dedifferentiated chondrosarcoma characterized by dedifferentiated components of malignant fibrous histiocytoma- or osteosarcoma-like features in addition to conventional chondrosarcoma, arising from his pelvic bone. After hemipelvectomy, when local recurrence and metastasis were identified, leukocytosis appeared and an elevated level of serum granulocyte-colony-stimulating factor (G-CSF was also recognized. The patient died of multiple organ failure 2 months after surgery. Autopsy specimens showed that the histological specimens of the recurrence and metastasis were dedifferentiated components, without any conventional chondrosarcoma components. G-CSF was expressed only in the dedifferentiated components, not in the chondrosarcoma components, immunohistochemically. Conclusion This is the first report of chondrosarcoma, or any other primary bone tumor, with leukocytosis, probably stimulated by tumor-produced G-CSF from the dedifferentiated components.

  18. Evaluating human cancer cell metastasis in zebrafish

    International Nuclear Information System (INIS)

    Teng, Yong; Xie, Xiayang; Walker, Steven; White, David T; Mumm, Jeff S; Cowell, John K

    2013-01-01

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

  19. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

    OpenAIRE

    Hayato Fukusumi; Tomoko Shofuda; Yohei Bamba; Atsuyo Yamamoto; Daisuke Kanematsu; Yukako Handa; Keisuke Okita; Masaya Nakamura; Shinya Yamanaka; Hideyuki Okano; Yonehiro Kanemura

    2016-01-01

    Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPS...

  20. Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Pechoux, Christine; Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Bissell, Mina J; Petersen, Ole

    1999-02-01

    The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and {alpha}-smooth muscle actin. We used a previously devised culture medium (CDM4) that allows vigorous expansion of proliferative myoepithelial cells and also devised a medium (CDM6) that allowed sufficient expansion of differentiated luminal epithelial cells based on addition of hepatocyte growth factor/scatter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cultures where we switched culture media, thus testing the ability of each lineage to convert to the other. Whereas the myoepithelial lineage showed no signs of interconversion, a subset of luminal epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We propose that in the mature human breast, it is the luminal epithelial cell compartment that gives rise to myoepithelial cells rather than the other way around.

  1. 3 CFR - Guidelines for Human Stem Cell Research

    Science.gov (United States)

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Guidelines for Human Stem Cell Research Presidential Documents Other Presidential Documents Memorandum of July 30, 2009 Guidelines for Human Stem Cell Research..., scientifically worthy human stem cell research, including human embryonic stem cell research, to the extent...

  2. 21 CFR 864.2280 - Cultured animal and human cells.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cultured animal and human cells. 864.2280 Section... Cultured animal and human cells. (a) Identification. Cultured animal and human cells are in vitro cultivated cell lines from the tissue of humans or other animals which are used in various diagnostic...

  3. Cell pattern in adult human corneal endothelium.

    Directory of Open Access Journals (Sweden)

    Carlos H Wörner

    Full Text Available A review of the current data on the cell density of normal adult human endothelial cells was carried out in order to establish some common parameters appearing in the different considered populations. From the analysis of cell growth patterns, it is inferred that the cell aging rate is similar for each of the different considered populations. Also, the morphology, the cell distribution and the tendency to hexagonallity are studied. The results are consistent with the hypothesis that this phenomenon is analogous with cell behavior in other structures such as dry foams and grains in polycrystalline materials. Therefore, its driving force may be controlled by the surface tension and the mobility of the boundaries.

  4. Merkel cell distribution in the human eyelid

    Directory of Open Access Journals (Sweden)

    C.A. May

    2013-10-01

    Full Text Available Although Merkel cell carcinoma of the eye lid is reported frequently in the literature, only limited information exists about the distribution of Merkel cells in this tissue. Therefore, serial sections of 18 human cadaver eye lids (donors ages ranging between 63 and 97 years were stained for cytokeratin 20 in various planes. The overall appearance of Merkel cells in these samples was low and mainly located in the outer root layer of the cilia hair follicles. Merkel cells were more frequent in the middle, and almost not detectable at the nasal and temporal edges. The localization is in accordance with that of Merkel cell carcinoma, but concerning the scarce appearance within this adulthood group, a specific physiological role of these cells in the eye lid is difficult to establish.

  5. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    Zwaan, F.E.

    1980-01-01

    The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

  6. T-cell response in human leishmaniasis

    DEFF Research Database (Denmark)

    Kharazmi, A; Kemp, K; Ismail, A

    1999-01-01

    In the present communication we provide evidence for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis. Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients. Lymphocytes from individuals recovered...... from cutaneous leishmaniasis (CL) responded by IFN-gamma production following stimulation with Leishmania antigens whereas cells from patients recovered from visceral leishmaniasis (VL) showed a mixed pattern of IFN-gamma and IL-4 responses. The cells producing these cytokines were predominantly CD4......+. Furthermore, IL-10 plays an important role in the development of post kala azar dermal leishmaniasis (PKDL) from VL. The balance between the parasitic-specific T-cell response plays an important regulatory role in determining the outcome of Leishmania infections in humans....

  7. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Chen Chang-Jie

    2010-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

  8. Primary mesenchymal chondrosarcoma of the kidney: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Pedro Valente

    2018-01-01

    Full Text Available Primary mesenchymal chondrosarcoma of the kidney is extremely rare, with only nine cases reported in the English literature. We report a new case of this disease. A 35-year-old man, presented with flank pain, episodic gross hematuria and a painless palpable mass in left abdominal quadrant. Computed tomography scan identified a left renal tumor with 20 cm, with no evidence of regional or metastatic spread disease. The patient underwent radical nephrectomy. The immunohistopathological diagnosis was mesenchymal chondrosarcoma of the kidney. At 18 months of follow-up, there was no evidence of recurrence or distant metastasis. Primary renal chondrosarcoma is so rare that its prognosis is unknown. Disease recurrence is unpredictable and when it is detected, the prognosis is poor. The radical nephrectomy with complete resection of the tumor with wide resection free margins is recommended, and the patients need long-term and close surveillance, with particular attention to local recurrence and uncommon sites of metastization.

  9. A High-Grade Chondrosarcoma of Calcaneum Mimicking as a Benign Pathology: Delayed Diagnosis and Management.

    Science.gov (United States)

    Baba, Muzamil Ahmad; Nazir, Naila; Shabeer, Maajid; Mir, Bashir Ahmed; Kawoosa, Altaf Ahmad

    2016-10-01

    This case is presented to highlight a rare case of chondrosarcoma of calcaneum in a young adult mimicking as a benign pathology and to highlight the diagnosis and early management of such cases to prevent complications and even death. Chondrosarcoma constitutes less than 10% of all primary malignancies of bone and occurs mostly in proximal locations such as pelvis, proximal femur, and proximal humerus. We present a case of high-grade chondrosarcoma at a very rare site, calcaneum of a 40-year-old male that was mimicking as a benign pathology. This case report highlights the importance of proper clinical examination, evaluation, and suspicion for benign occurring lesions to prevent complications related to a delay in diagnosis. Therapeutic, Level IV: Case study. © 2016 The Author(s).

  10. Use of MicroRNA biomarkers to distinguish enchondroma from low-grade chondrosarcoma.

    Science.gov (United States)

    Zhang, Liang; Yang, Maozhou; Mayer, Theodore; Johnstone, Brian; Les, Clifford; Frisch, Nicholas; Parsons, Theodore; Mi, Qing-Sheng; Gibson, Gary

    2017-03-01

    Establishing a definitive diagnosis between benign enchondroma versus low-grade chondrosarcoma presents a potential challenge to both clinicians and pathologists. microRNAs (small non-coding RNAs) have proven to be effective biomarkers for the identification of tumors and tumor progression. We present analysis, both array and quantitative PCR, that shows consistently and substantially increased expression of two microRNAs, miRs-181a and -138, in low-grade chondrosarcomas compared with enchondromas. The data suggest these microRNAs would provide an analytical distinction between the chondrosarcoma and benign neoplasms that can be performed in formalin-fixed paraffin-embedded specimens. Together with recent publications, these data indicate that miRs-181a and -138 also play a role in tumor development and homeostasis and may provide new targets for the development of much needed therapeutic intervention.

  11. Endoscopic Endonasal Approach in Skull Base Chondrosarcoma Associated with Maffucci Syndrome: Case Series and Literature Review.

    Science.gov (United States)

    Beer-Furlan, André; Balsalobre, Leonardo; Vellutini, Eduardo A S; Stamm, Aldo C

    2016-01-01

    Maffucci syndrome is a nonhereditary disorder in which patients develop multiple enchondromas and cutaneous, visceral, or soft tissue hemangiomas. The potential malignant progression of enchondroma into a secondary chondrosarcoma is a well-known fact. Nevertheless, chondrosarcoma located at the skull base in patients with Maffuci syndrome is a very rare condition, with only 18 cases reported in the literature. We report 2 other cases successfully treated through an expanded endoscopic endonasal approach and discuss the condition based on the literature review. Skull base chondrosarcoma associated with Maffucci syndrome is a rare condition. The disease cannot be cured, therefore surgical treatment should be performed in symptomatic patients aiming for maximal tumor resection with function preservation. The endoscopic endonasal approach is a safe and reliable alternative for the management of these tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Hyperkinetic transient ischemic attacks preceding deep ganglionic infarction in a patient with a treated parasellar chondrosarcoma.

    Science.gov (United States)

    Ruff, Michael W; Bhargav, Adip G; English, Stephen W; Klaas, James P

    2018-02-01

    A 44-year-old right-handed female with a past medical history of parasellar chondrosarcoma status post-surgical debulking and proton beam therapy (70 Gy) three years prior to presentation experienced several hours of brief, repetitive episodes of transient hemiballism and dystonia; this was followed by abrupt onset of fixed hemiparesis and dysarthria weeks later, ipsilateral to her prior hyperkinetic movements. She was found to have total occlusion of the right middle cerebral artery with focal stenosis of the proximal right A-1 segment of the anterior cerebral artery adjacent to the remnants of the chondrosarcoma. These focal areas of narrowing were attributed to accelerated atherosclerotic disease, an adverse effect of the radiotherapy used to treat her chondrosarcoma. As treatments improve and mean survival increases for intracranial malignancy, radiation-induced atherosclerotic disease with protean manifestations such as those presented in this case may be encountered more frequently. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Zoledronic acid in metastatic chondrosarcoma and advanced sacrum chordoma: two case reports

    Directory of Open Access Journals (Sweden)

    Capasso Elena

    2009-01-01

    Full Text Available Abstract Introduction Chondrosarcomas and chordomas are usually chemoresistant bone tumors and may have a poor prognosis when advanced. They are usually associated with worsening pain difficult to control. Patients and Methods Zoledronic acid was used in a 63-year-old man with metastatic chondrosarcoma and in a 66-year-old woman with a diagnosis of sacrum chordoma both reporting severe pain related to tumor. Results In the first case, zoledronic acid was able to maintain pain control despite disease progression following chemotherapy, in the other case, zoledronic acid only produced significant clinical benefit. Conclusion Control of pain associated with bone tumors such as chondrosarcoma and chondroma may significantly improve from use of zoledronic acid, independently from tumor response to other treatments. Evaluation on larger series are needed to confirm the clinical effect of this bisphosphonate on such tumors.

  14. Radiation-induced chondrosarcoma of the maxilla 7-year after combined chemoradiation for tonsillar lymphoma.

    Science.gov (United States)

    Mohammadianpanah, M; Gramizadeh, B; Omidvari, Sh; Mosalaei, A

    2004-01-01

    Radiation-induced sarcoma is a rare complication of radiation therapy. We report a case of radiation-induced chondrosarcoma of the maxilla. An 80-year-old Persian woman developed radiation-induced chondrosarcoma of the left maxilla 7 years after combined chemotherapy and external beam radiation therapy for the Ann Arbor stage IE malignant lymphoma of the right tonsil. She underwent suboptimal tumour resection and died due to extensive locoregional disease 8 months later. An English language literature search of Medline using the terms chondrosarcoma, radiation-induced sarcoma and maxilla revealed only one earlier reported case. We describe the clinical and pathological features of this case and review the literature on radiation-induced sarcomas.

  15. Radiation-induced chondrosarcoma of the maxilla 7-year after combined chemoradiation for tonsillar lymphoma

    Directory of Open Access Journals (Sweden)

    Mohammadianpanah M

    2004-07-01

    Full Text Available Radiation-induced sarcoma is a rare complication of radiation therapy. We report a case of radiation-induced chondrosarcoma of the maxilla. An 80-year-old Persian woman developed radiation-induced chondrosarcoma of the left maxilla 7 years after combined chemotherapy and external beam radiation therapy for the Ann Arbor stage IE malignant lymphoma of the right tonsil. She underwent suboptimal tumour resection and died due to extensive locoregional disease 8 months later. An English language literature search of Medline using the terms chondrosarcoma, radiation-induced sarcoma and maxilla revealed only one earlier reported case. We describe the clinical and pathological features of this case and review the literature on radiation-induced sarcomas.

  16. [Hemothorax caused by primary pleural chondrosarcoma: a case report and review of literatureYuan].

    Science.gov (United States)

    Yuan, Y Q; Zhu, L Y; Zeng, H H; Zhou, R; Chen, P

    2016-11-12

    Objective: To analyze the clinical features of one case of spontaneous hemothorax caused by primary pleural chondrosarcoma and therefore to improve the understanding of this disease. Methods: The clinical features of a case with primary pleural chondrosarcoma were analyzed retrospectively and the related literatures were reviewed.The literature review was carried out with "primary pleural, chondrosarcoma" in Chinese and English respectively, as the search terms in Wanfang Data, CNKI and PubMed database from January 1980 to October 2015. A total of 6 articales, 1 in Chinese and 5 in English, were reviewed. Results: A 29 year-old male patient was admitted to the hospital because of fever, chest tightness, shortness of breath for 20 days. CT scan of the chest showed a mass near the right posterior fourth rib and right pleural effusion.Routine examination of the pleural effusion confirmed the presence of hemothorax. Thoracotomy was performed and revealed hemothorax in the right thorax, and a mass near the pleural apex. The tumor was removed by surgery and pleural decortication was also performed. Pathology study confirmed the diagnosis of high-differentiated chondrosarcoma. The patient was followed and there was no recurrence until now. A total of 6 case reports were retrieved from Wanfang Data, CNKI and PubMed. Five cases had complete data, including 2 males and 3 females(age from 28 to70), and another (a 78-year old male) without adequate data. Conclusions: Primary pleural chondrosarcoma is a rare disease, and hemothorax as the first manifestation is even rare. It is easily to be misdiagnosed due to nonspecific clinical symptoms.The final diagnosis depends ultimately on pathological biopsy. Thoracotomy is the most effective method for treatment of primary pleural chondrosarcoma.

  17. Shape Memory of Human Red Blood Cells

    OpenAIRE

    Fischer, Thomas M.

    2004-01-01

    The human red cell can be deformed by external forces but returns to the biconcave resting shape after removal of the forces. If after such shape excursions the rim is always formed by the same part of the membrane, the cell is said to have a memory of its biconcave shape. If the rim can form anywhere on the membrane, the cell would have no shape memory. The shape memory was probed by an experiment called go-and-stop. Locations on the membrane were marked by spontaneously adhering latex spher...

  18. Human embryonic stem cell lines model experimental human cytomegalovirus latency.

    Science.gov (United States)

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

    Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

  19. Human embryonic stem cells: preclinical perspectives

    Directory of Open Access Journals (Sweden)

    Sarda Kanchan

    2008-01-01

    Full Text Available Abstract Human embryonic stem cells (hESCs have been extensively discussed in public and scientific communities for their potential in treating diseases and injuries. However, not much has been achieved in turning them into safe therapeutic agents. The hurdles in transforming hESCs to therapies start right with the way these cells are derived and maintained in the laboratory, and goes up-to clinical complications related to need for patient specific cell lines, gender specific aspects, age of the cells, and several post transplantation uncertainties. The different types of cells derived through directed differentiation of hESC and used successfully in animal disease and injury models are described briefly. This review gives a brief outlook on the present and the future of hESC based therapies, and talks about the technological advances required for a safe transition from laboratory to clinic.

  20. Neocortical glial cell numbers in human brains

    DEFF Research Database (Denmark)

    Pelvig, D.P.; Pakkenberg, H.; Stark, A.K.

    2008-01-01

    Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia...... while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males...... and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons...

  1. Dedifferentiated chondrosarcoma with "adamantinoma-like" features: A case report and review of literature.

    Science.gov (United States)

    Gambarotti, M; Righi, A; Frisoni, T; Donati, D; Vanel, D; Sbaraglia, M; Dei Tos, A P

    2017-06-01

    Dedifferentiated chondrosarcoma is defined by the presence of a low grade malignant cartilaginous component juxtaposed to a high grade malignant non-cartilaginous sarcomatous components. Only 4 cases in which the high grade component showed epithelial differentiation have been reported in the literature; three featured a squamous and the one a glandular epithelial component. Here we describe a case of dedifferentiated chondrosarcoma exhibiting epithelial "adamantinoma-like" basaloid features. The patient underwent wide resection of the proximal tibia and post-operative chemotherapy and died 8 months after the diagnosis due to lung and bone metastases. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. Chondromyxoid fibroma of the rib mimics a chondrosarcoma on 18F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William (Dept. of Nuclear Medicine, Brandon Regional Health Centre, Brandon (Canada)), email: makisw79@yahoo.com; Ciarallo, Anthony; Lisbona, Robert (Dept. of Nuclear Medicine, Royal Victoria Hospital, McGill Univ. Health Centre, Montreal (Canada))

    2011-06-15

    Chondromyxoid fibroma (CMF) is a rare benign bone tumor of chondroid origin that occurs mostly in the metaphyses of long bones. CMF can occasionally mimic a chondrosarcoma on CT, and the literature on the 18F-FDG PET/CT imaging characteristics of CMF tumors is limited. In the presented case, a large histologically proven CMF chest wall mass was initially misinterpreted as a chondrosarcoma. This case highlights a potential pitfall in the PET/CT evaluation of these rare benign bone tumors

  3. Tyrosine kinase inhibitor SU6668 represses chondrosarcoma growth via antiangiogenesis in vivo

    International Nuclear Information System (INIS)

    Klenke, Frank M; Abdollahi, Amir; Bertl, Elisabeth; Gebhard, Martha-Maria; Ewerbeck, Volker; Huber, Peter E; Sckell, Axel

    2007-01-01

    As chondrosarcomas are resistant to chemotherapy and ionizing radiation, therapeutic options are limited. Radical surgery often cannot be performed. Therefore, additional therapies such as antiangiogenesis represent a promising strategy for overcoming limitations in chondrosarcoma therapy. There is strong experimental evidence that SU6668, an inhibitor of the angiogenic tyrosine kinases Flk-1/KDR, PDGFRbeta and FGFR1 can induce growth inhibition of various primary tumors. However, the effectiveness of SU6668 on malignant primary bone tumors such as chondrosarcomas has been rarely investigated. Therefore, the aim of this study was to investigate the effects of SU6668 on chondrosarcoma growth, angiogenesis and microcirculation in vivo. In 10 male severe combined immunodeficient (SCID) mice, pieces of SW1353 chondrosarcomas were implanted into a cranial window preparation where the calvaria serves as the site for the orthotopic implantation of bone tumors. From day 7 after tumor implantation, five animals were treated with SU6668 (250 mg/kg body weight, s.c.) at intervals of 48 hours (SU6668), and five animals with the equivalent amount of the CMC-based vehicle (Control). Angiogenesis, microcirculation, and growth of SW 1353 tumors were analyzed by means of intravital microscopy. SU6668 induced a growth arrest of chondrosarcomas within 7 days after the initiation of the treatment. Compared to Controls, SU6668 decreased functional vessel density and tumor size, respectively, by 37% and 53% on day 28 after tumor implantation. The time course of the experiments demonstrated that the impact on angiogenesis preceded the anti-tumor effect. Histological and immunohistochemical results confirmed the intravital microscopy findings. SU6668 is a potent inhibitor of chondrosarcoma tumor growth in vivo. This effect appears to be induced by the antiangiogenic effects of SU6668, which are mediated by the inhibition of the key angiogenic receptor tyrosine kinases Flk-1/KDR, PDGFRbeta

  4. Endoscopic Endonasal Infrapetrous Transpterygoid Approach to the Petroclival Junction for Petrous Apex Chondrosarcoma: Technical Report.

    Science.gov (United States)

    Maurer, Adrian J; Bonney, Phillip A; Iser, Courtney R; Ali, Rohaid; Sanclement, Jose A; Sughrue, Michael E

    2015-07-01

    Chondrosarcomas of the skull base are rare tumors that present difficult management considerations due to the pathoanatomical relationships of the tumor to adjacent structures. We present the case of a 25-year-old female patient presenting with a chondrosarcoma of the right petrous apex extending inferiorly, medial to the cranial nerves. The tumor was resected via an endoscopic endonasal infrapetrous transpterygoid approach that achieved complete resection and an excellent long-term outcome with no complications. Technical nuances and potential pitfalls of the case are discussed in depth including measures to protect the carotid artery while performing the required drilling of the skull base to access the lesion.

  5. Melanopsin expressing human retinal ganglion cells

    DEFF Research Database (Denmark)

    Hannibal, Jens; Christiansen, Anders Tolstrup; Heegaard, Steffen

    2017-01-01

    microscopy and 3D reconstruction of melanopsin immunoreactive (-ir) RGCs, we applied the criteria used in mouse on human melanopsin-ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of melanopsin-ir RGCs, which were named "gigantic M1 (GM1)" and "gigantic displaced M1...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-12-01

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

  7. Clinical potentials of human pluripotent stem cells.

    Science.gov (United States)

    Mora, Cristina; Serzanti, Marialaura; Consiglio, Antonella; Memo, Maurizio; Dell'Era, Patrizia

    2017-08-01

    Aging, injuries, and diseases can be considered as the result of malfunctioning or damaged cells. Regenerative medicine aims to restore tissue homeostasis by repairing or replacing cells, tissues, or damaged organs, by linking and combining different disciplines including engineering, technology, biology, and medicine. To pursue these goals, the discipline is taking advantage of pluripotent stem cells (PSCs), a peculiar type of cell possessing the ability to differentiate into every cell type of the body. Human PSCs can be isolated from the blastocysts and maintained in culture indefinitely, giving rise to the so-called embryonic stem cells (ESCs). However, since 2006, it is possible to restore in an adult cell a pluripotent ESC-like condition by forcing the expression of four transcription factors with the rejuvenating reprogramming technology invented by Yamanaka. Then the two types of PSC can be differentiated, using standardized protocols, towards the cell type necessary for the regeneration. Although the use of these derivatives for therapeutic transplantation is still in the preliminary phase of safety and efficacy studies, a lot of efforts are presently taking place to discover the biological mechanisms underlying genetic pathologies, by differentiating induced PSCs derived from patients, and new therapies by challenging PSC-derived cells in drug screening.

  8. Pigment Production Analysis in Human Melanoma Cells.

    Science.gov (United States)

    Hopkin, Amelia Soto; Paterson, Elyse K; Ruiz, Rolando; Ganesan, Anand K

    2016-05-25

    The human epidermal melanocyte is a highly specialized pigmented cell that serves to protect the epidermis from ultraviolet (UV) damage through the production of melanin, or melanogenesis. Misregulation in melanogenesis leading to either hyper- or hypo-pigmentation is found in human diseases such as malasma and vitiligo. Current therapies for these diseases are largely unsuccessful and the need for new therapies is necessary. In order to identify genes and or compounds that can alter melanogenesis, methods are required that can detect changes in pigment production as well as expression of key melanogenesis transcription factors and enzymes. Here we describe methods to detect changes in melanogenesis in a human melanoma cell line, MNT-1, by (1) analyzing pigment production by measuring the absorbance of melanin present by spectrophotometry, (2) analyzing transcript expression of potent regulators of melanogenesis by qunatitative reverse-transcription (RT)PCR and (3) analyzing protein expression of potent regulators of melanogenesis by Western blot (WB).

  9. Human T Cell Memory: A Dynamic View

    Directory of Open Access Journals (Sweden)

    Derek C. Macallan

    2017-02-01

    Full Text Available Long-term T cell-mediated protection depends upon the formation of a pool of memory cells to protect against future pathogen challenge. In this review we argue that looking at T cell memory from a dynamic viewpoint can help in understanding how memory populations are maintained following pathogen exposure or vaccination. For example, a dynamic view resolves the apparent paradox between the relatively short lifespans of individual memory cells and very long-lived immunological memory by focussing on the persistence of clonal populations, rather than individual cells. Clonal survival is achieved by balancing proliferation, death and differentiation rates within and between identifiable phenotypic pools; such pools correspond broadly to sequential stages in the linear differentiation pathway. Each pool has its own characteristic kinetics, but only when considered as a population; single cells exhibit considerable heterogeneity. In humans, we tend to concentrate on circulating cells, but memory T cells in non-lymphoid tissues and bone marrow are increasingly recognised as critical for immune defence; their kinetics, however, remain largely unexplored. Considering vaccination from this viewpoint shifts the focus from the size of the primary response to the survival of the clone and enables identification of critical system pinch-points and opportunities to improve vaccine efficacy.

  10. Image-guided, intensity-modulated radiation therapy (IG-IMRT) for skull base chordoma and chondrosarcoma: preliminary outcomes.

    Science.gov (United States)

    Sahgal, Arjun; Chan, Michael W; Atenafu, Eshetu G; Masson-Cote, Laurence; Bahl, Gaurav; Yu, Eugene; Millar, Barbara-Ann; Chung, Caroline; Catton, Charles; O'Sullivan, Brian; Irish, Jonathan C; Gilbert, Ralph; Zadeh, Gelareh; Cusimano, Michael; Gentili, Fred; Laperriere, Normand J

    2015-06-01

    We report our preliminary outcomes following high-dose image-guided intensity modulated radiotherapy (IG-IMRT) for skull base chordoma and chondrosarcoma. Forty-two consecutive IG-IMRT patients, with either skull base chordoma (n = 24) or chondrosarcoma (n = 18) treated between August 2001 and December 2012 were reviewed. The median follow-up was 36 months (range, 3-90 mo) in the chordoma cohort, and 67 months (range, 15-125) in the chondrosarcoma cohort. Initial surgery included biopsy (7% of patients), subtotal resection (57% of patients), and gross total resection (36% of patients). The median IG-IMRT total doses in the chondrosarcoma and chordoma cohorts were 70 Gy and 76 Gy, respectively, delivered with 2 Gy/fraction. For the chordoma and chondrosarcoma cohorts, the 5-year overall survival and local control rates were 85.6% and 65.3%, and 87.8% and 88.1%, respectively. In total, 10 patients progressed locally: 8 were chordoma patients and 2 chondrosarcoma patients. Both chondrosarcoma failures were in higher-grade tumors (grades 2 and 3). None of the 8 patients with grade 1 chondrosarcoma failed, with a median follow-up of 77 months (range, 34-125). There were 8 radiation-induced late effects-the most significant was a radiation-induced secondary malignancy occurring 6.7 years following IG-IMRT. Gross total resection and age were predictors of local control in the chordoma and chondrosarcoma patients, respectively. We report favorable survival, local control and adverse event rates following high dose IG-IMRT. Further follow-up is needed to confirm long-term efficacy. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Development and function of human innate immune cells in a humanized mouse model.

    Science.gov (United States)

    Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V; Teichmann, Lino L; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A Karolina; Manz, Markus G; Flavell, Richard A

    2014-04-01

    Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

  12. Chondrosarcoma of right 1st rib presenting as neurogenic thoracic outlet syndrome; A 13th case report in world literature

    Directory of Open Access Journals (Sweden)

    Ravisagar Patel

    2016-07-01

    Full Text Available Thoracic outlet syndrome [TOS] caused by a tumor of the rib is rare and has been reported only 12 times in the literature over the past one and one-half centuries, with the majority of cases due to osteochondroma. We report a case of chondrosarcoma of right 1st rib causing neurogenic TOS that was resected via posterolateral thoracotomy and biopsy confirmed a grade I chondrosarcoma. In the treatment of chondrosarcoma, chemotherapy and radiotherapy are less effective, and appropriate surgery is needed.

  13. Isolation of Human Skin Dendritic Cell Subsets.

    Science.gov (United States)

    Gunawan, Merry; Jardine, Laura; Haniffa, Muzlifah

    2016-01-01

    Dendritic cells (DCs) are specialized leukocytes with antigen-processing and antigen-presenting functions. DCs can be divided into distinct subsets by anatomical location, phenotype and function. In human, the two most accessible tissues to study leukocytes are peripheral blood and skin. DCs are rare in human peripheral blood (skin covering an average total surface area of 1.8 m(2) has approximately tenfold more DCs than the average 5 L of total blood volume (Wang et al., J Invest Dermatol 134:965-974, 2014). DCs migrate spontaneously from skin explants cultured ex vivo, which provide an easy method of cell isolation (Larsen et al., J Exp Med 172:1483-1493, 1990; Lenz et al., J Clin Invest 92:2587-2596, 1993; Nestle et al., J Immunol 151:6535-6545, 1993). These factors led to the extensive use of skin DCs as the "prototype" migratory DCs in human studies. In this chapter, we detail the protocols to isolate DCs and resident macrophages from human skin. We also provide a multiparameter flow cytometry gating strategy to identify human skin DCs and to distinguish them from macrophages.

  14. Neocortical glial cell numbers in human brains.

    Science.gov (United States)

    Pelvig, D P; Pakkenberg, H; Stark, A K; Pakkenberg, B

    2008-11-01

    Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex.

  15. The Human Cell Surfaceome of Breast Tumors

    Science.gov (United States)

    da Cunha, Júlia Pinheiro Chagas; Galante, Pedro Alexandre Favoretto; de Souza, Jorge Estefano Santana; Pieprzyk, Martin; Carraro, Dirce Maria; Old, Lloyd J.; Camargo, Anamaria Aranha; de Souza, Sandro José

    2013-01-01

    Introduction. Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface. Methods. We used a high-throuput qPCR system for the analysis of 573 cell surface protein-coding genes in 12 primary breast tumors, 8 breast cell lines, and 21 normal human tissues including breast. To better understand the role of these genes in breast tumors, we used a series of bioinformatics strategies to integrates different type, of the datasets, such as KEGG, protein-protein interaction databases, ONCOMINE, and data from, literature. Results. We found that at least 77 genes are overexpressed in breast primary tumors while at least 2 of them have also a restricted expression pattern in normal tissues. We found common signaling pathways that may be regulated in breast tumors through the overexpression of these cell surface protein-coding genes. Furthermore, a comparison was made between the genes found in this report and other genes associated with features clinically relevant for breast tumorigenesis. Conclusions. The expression profiling generated in this study, together with an integrative bioinformatics analysis, allowed us to identify putative targets for breast tumors. PMID:24195083

  16. Shape memory of human red blood cells.

    Science.gov (United States)

    Fischer, Thomas M

    2004-05-01

    The human red cell can be deformed by external forces but returns to the biconcave resting shape after removal of the forces. If after such shape excursions the rim is always formed by the same part of the membrane, the cell is said to have a memory of its biconcave shape. If the rim can form anywhere on the membrane, the cell would have no shape memory. The shape memory was probed by an experiment called go-and-stop. Locations on the membrane were marked by spontaneously adhering latex spheres. Shape excursions were induced by shear flow. In virtually all red cells, a shape memory was found. After stop of flow and during the return of the latex spheres to the original location, the red cell shape was biconcave. The return occurred by a tank-tread motion of the membrane. The memory could not be eliminated by deforming the red cells in shear flow up to 4 h at room temperature as well as at 37 degrees C. It is suggested that 1). the characteristic time of stress relaxation is >80 min and 2). red cells in vivo also have a shape memory.

  17. Human somatic cell nuclear transfer and cloning.

    Science.gov (United States)

    2012-10-01

    This document presents arguments that conclude that it is unethical to use somatic cell nuclear transfer (SCNT) for infertility treatment due to concerns about safety; the unknown impact of SCNT on children, families, and society; and the availability of other ethically acceptable means of assisted reproduction. This document replaces the ASRM Ethics Committee report titled, "Human somatic cell nuclear transfer (cloning)," last published in Fertil Steril 2000;74:873-6. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

    Directory of Open Access Journals (Sweden)

    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  19. Is Needle Biopsy Clinically Useful in Preoperative Grading of Central Chondrosarcoma of the Pelvis and Long Bones?

    Science.gov (United States)

    Roitman, Pablo D; Farfalli, Germán L; Ayerza, Miguel A; Múscolo, D Luis; Milano, Federico E; Aponte-Tinao, Luis A

    2017-03-01

    Central chondrosarcoma of bone is graded on a scale of 1 to 3 according to histological criteria. Clinically, these tumors can be divided into low-grade (Grade 1) and high-grade (Grade 2, Grade 3, and dedifferentiated) chondrosarcomas. Although en bloc resection has been the most widely used treatment, it has become generally accepted that in selected patients with low-grade chondrosarcomas of long bones, curettage is safe and effective. This approach requires an accurate preoperative estimation of grade to avoid under- or overtreatment, but prior reports have indicated that both imaging and biopsy do not always give an accurate prediction of grade. (1) What is the concordance of image-guided needle preoperative biopsy and postoperative grading in central (intramedullary) chondrosarcomas of long bones, and how does this compare with the concordance of image-guided needle preoperative biopsy and postoperative grading in central pelvic chondrosarcomas? (2) What is the concordance of preoperative image-guided needle biopsy and postoperative findings in differentiating low-grade from high-grade central chondrosarcomas of long bones, and how does this compare with the concordance in central pelvic chondrosarcomas? Between 1997 and 2014, in our institution, we treated 126 patients for central chondrosarcomas located in long bones and the pelvis. Of these 126 cases, 41 were located in the pelvis and the remaining 85 cases were located in long bones. This study considers 39 (95%) and 40 (47%) of them, respectively. We included all cases in which histological information was complete regarding preoperative and postoperative tumor grading. We excluded all cases with incomplete data sets or nondiagnostic preoperative biopsies. To evaluate the needle biopsy accuracy, we compared the histological tumor grade, obtained from the preoperative biopsy, with the final histological grade obtained from the postoperative surgical specimen. The weighted and nonweighted kappa statistics

  20. Dopamine receptor repertoire of human granulosa cells

    Directory of Open Access Journals (Sweden)

    Kunz Lars

    2007-10-01

    Full Text Available Abstract Background High levels of dopamine (DA were described in human ovary and recently evidence for DA receptors in granulosa and luteal cells has been provided, as well. However, neither the full repertoire of ovarian receptors for DA, nor their specific role, is established. Human granulosa cells (GCs derived from women undergoing in vitro fertilization (IVF are an adequate model for endocrine cells of the follicle and the corpus luteum and were therefore employed in an attempt to decipher their DA receptor repertoire and functionality. Methods Cells were obtained from patients undergoing IVF and examined using cDNA-array, RT-PCR, Western blotting and immunocytochemistry. In addition, calcium measurements (with FLUO-4 were employed. Expression of two DA receptors was also examined by in-situ hybridization in rat ovary. Effects of DA on cell viability and cell volume were studied by using an ATP assay and an electronic cell counter system. Results We found members of the two DA receptor families (D1- and D2 -like associated with different signaling pathways in human GCs, namely D1 (as expected and D5 (both are Gs coupled and linked to cAMP increase and D2, D4 (Gi/Gq coupled and linked to IP3/DAG. D3 was not found. The presence of the trophic hormone hCG (10 IU/ml in the culture medium for several days did not alter mRNA (semiquantitative RT-PCR or protein levels (immunocytochemistry/Western blotting of D1,2,4,5 DA receptors. Expression of prototype receptors for the two families, D1 and D2, was furthermore shown in rat granulosa and luteal cells by in situ hybridization. Among the DA receptors found in human GCs, D2 expression was marked both at mRNA and protein levels and it was therefore further studied. Results of additional RT-PCR and Western blots showed two splice variants (D2L, D2S. Irrespective of these variants, D2 proved to be functional, as DA raised intracellular calcium levels. This calcium mobilizing effect of DA was observed

  1. Some Ethical Concerns About Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Zheng, Yue Liang

    2016-10-01

    Human induced pluripotent stem cells can be obtained from somatic cells, and their derivation does not require destruction of embryos, thus avoiding ethical problems arising from the destruction of human embryos. This type of stem cell may provide an important tool for stem cell therapy, but it also results in some ethical concerns. It is likely that abnormal reprogramming occurs in the induction of human induced pluripotent stem cells, and that the stem cells generate tumors in the process of stem cell therapy. Human induced pluripotent stem cells should not be used to clone human beings, to produce human germ cells, nor to make human embryos. Informed consent should be obtained from patients in stem cell therapy.

  2. Coronary artery bypass grafting and concomitant excision of chest wall chondrosarcoma

    Directory of Open Access Journals (Sweden)

    Ganti Somsekhar

    2009-02-01

    Full Text Available Abstract Coexistence of coronary artery disease and cancer with both requiring surgical treatment at the same time is rare. A 52 year male undergoing elective coronary artery bypass grafting was incidentally discovered to have a large soft tissue mass of variable consistency with cartilaginous elements arising from the right costal margin and adjoining ribs by a broad attachment and protruding into right pleural cavity. Frozen section suggested it to be either a chondrosarcoma or a teratoma. A wide excision of the mass with the adjoining muscle and periosteum along with quadruple coronary artery bypass grafting was done. This report is unusual on account of a being the first reported case in world literature of concomitant excision of chondrosarcoma and coronary artery bypass grafting and b the conservative management of the incidentally discovered chondrosarcoma by wide excision rather than chest wall resection with no local recurrence to date. Pathology of chondrosarcoma, in particular, and various management strategies when coronary artery disease and cancer coexist, in general, is discussed.

  3. Chordoma versus chondrosarcoma of the central skull base: MR and CT findings

    International Nuclear Information System (INIS)

    Choi, Guk Myeong; Han, Moon Hee; Chang, Kee Hyun; Kim, Hong Dae; Yeon, Kyung Mo; Kim, Sam Soo

    1998-01-01

    It is known that due to both their imaging and pathologic features, the accurate differentiation of chondrosarcoma from chordoma is difficult. Through an analysis of MR and CT finding, this study aims to determine the differential points between these two tumors. In 21 patients, CT and MR imaging studies of chordoma (n=12) and chondrosarcoma (n=9) at the base of the skull were retrospectively reviewed. Diagnosis had been established by histologic examination of surgically removed specimens. Eleven of the chordomas were subclassified as conventional and one as chondroid ; eight chondrosarcoma were conventional and one was myxoid. Four chordoma patients underwent CT and MR ; in six, only MR was in one, only CT was performed. All scans were retrospectively evaluated for the location (midline/off-midline), direction of extension, margin and shape, bony destruction and calcification, MR signal intensity and enhancement patterns of the tumors. Degree of calcification was graded from I to II. Although MR and CT findings were similar in both types of tumor, location and degree of calcification may be features which usefully distinguish chordoma from chondrosarcoma. (author). 17 refs., 2 tabs., 5 figs

  4. Unique mutation portraits and frequent COL2A1 gene alteration in chondrosarcoma

    Science.gov (United States)

    Totoki, Yasushi; Yoshida, Akihiko; Hosoda, Fumie; Nakamura, Hiromi; Hama, Natsuko; Ogura, Koichi; Yoshida, Aki; Fujiwara, Tomohiro; Arai, Yasuhito; Toguchida, Junya; Tsuda, Hitoshi; Miyano, Satoru; Kawai, Akira

    2014-01-01

    Chondrosarcoma is the second most frequent malignant bone tumor. However, the etiological background of chondrosarcomagenesis remains largely unknown, along with details on molecular alterations and potential therapeutic targets. Massively parallel paired-end sequencing of whole genomes of 10 primary chondrosarcomas revealed that the process of accumulation of somatic mutations is homogeneous irrespective of the pathological subtype or the presence of IDH1 mutations, is unique among a range of cancer types, and shares significant commonalities with that of prostate cancer. Clusters of structural alterations localized within a single chromosome were observed in four cases. Combined with targeted resequencing of additional cartilaginous tumor cohorts, we identified somatic alterations of the COL2A1 gene, which encodes an essential extracellular matrix protein in chondroskeletal development, in 19.3% of chondrosarcoma and 31.7% of enchondroma cases. Epigenetic regulators (IDH1 and YEATS2) and an activin/BMP signal component (ACVR2A) were recurrently altered. Furthermore, a novel FN1-ACVR2A fusion transcript was observed in both chondrosarcoma and osteochondromatosis cases. With the characteristic accumulative process of somatic changes as a background, molecular defects in chondrogenesis and aberrant epigenetic control are primarily causative of both benign and malignant cartilaginous tumors. PMID:25024164

  5. Radiotherapy for chordomas and low-grade chondrosarcomas of the skull base with carbon ions

    International Nuclear Information System (INIS)

    Schulz-Ertner, Daniela; Haberer, Thomas; Jaekel, Oliver; Thilmann, Christoph; Kraemer, Michael; Enghardt, Wolfgang; Kraft, Gerhard; Wannenmacher, Michael; Debus, Juergen

    2002-01-01

    Purpose: Compared to photon irradiation, carbon ions provide physical and biologic advantages that may be exploited in chordomas and chondrosarcomas. Methods and Materials: Between August 1998 and December 2000, 37 patients with chordomas (n=24) and chondrosarcomas (n=13) were treated with carbon ion radiotherapy within a Phase I/II trial. Tumor conformal application of carbon ion beams was realized by intensity-controlled raster scanning with pulse-to-pulse energy variation. Three-dimensional treatment planning included biologic plan optimization. The median tumor dose was 60 GyE (GyE Gy x relative biologic effectiveness). Results: The mean follow-up was 13 months. The local control rate after 1 and 2 years was 96% and 90%, respectively. We observed 2 recurrences outside the gross tumor volume in patients with chordomas. Progression-free survival was 100% for chondrosarcomas and 83% for chordomas at 2 years. Partial remission after carbon ion radiotherapy was observed in 6 patients. Treatment toxicity was mild. Conclusion: These are the first data demonstrating the clinical feasibility, safety, and effectiveness of scanning beam delivery of ion beams in patients with skull base tumors. The preliminary results in patients with skull base chordomas and low-grade chondrosarcomas are encouraging, although the follow-up was too short to draw definite conclusions concerning outcome. In the absence of major toxicity, dose escalation might be considered

  6. Comparison of clinical and functional outcome between surgical treatment and carbon ion radiotherapy for pelvic chondrosarcoma.

    Science.gov (United States)

    Outani, Hidetatsu; Hamada, Kenichiro; Imura, Yoshinori; Oshima, Kazuya; Sotobori, Tsukasa; Demizu, Yusuke; Kakunaga, Shigeki; Joyama, Susumu; Imai, Reiko; Okimoto, Tomoaki; Naka, Norifumi; Kudawara, Ikuo; Ueda, Takafumi; Araki, Nobuhito; Kamada, Tadashi; Yoshikawa, Hideki

    2016-02-01

    As there are no reports of studies in patients with pelvic chondrosarcoma treated with carbon ion radiotherapy (CIRT), the aim of this study was to evaluate the applicability of CIRT for patients with chondrosarcoma of the pelvis. The medical records of 31 patients with chondrosarcoma of the pelvis treated either by surgical resection or by CIRT between 1983 and 2014 were reviewed. There were 22 males and 9 females with a median age of 43 years (range 16-77 years). The median duration of follow-up was 66 months (range 5-289 months). Twenty-four patients underwent surgery, and 7 patients received CIRT (70.4 GyE in 16 fractions over 4 weeks). The overall local recurrence rate was 32 %, and the estimated overall 5- and 10-year survival rates were 72 and 57 %, respectively. The mean Musculoskeletal Tumor Society functional score was 59 %. The treatment procedures (surgery or CIRT) did not affect overall survival (P = 0.347). However, the patients who underwent surgery had impaired function compared with those who received CIRT (P = 0.03). Although more patients need to be monitored to assess the clinical and functional outcomes of CIRT for patients with chondrosarcoma of the pelvis, this treatment might offer an acceptable alternative.

  7. Periosteal chondrosarcoma in a 9-year-old girl with osteochondromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Weinberg, Jacob [Schneider Children' s Hospital, Division of Pediatric Orthopaedic Surgery, New York (United States); New York University/Hospital for Joint Diseases, Division of Orthopaedic Oncology, New York, New York (United States); Miller, Theodore T. [North Shore University Hospital, Department of Radiology, Manhasset, New York (United States); Handelsman, John E.; Godfried, David H. [Schneider Children' s Hospital, Division of Pediatric Orthopaedic Surgery, New York (United States); Kahn, Leonard B. [Long Island Jewish Medical Center, Department of Pathology, New Hyde Park, New York (United States); Kenan, Samuel [Schneider Children' s Hospital, Division of Pediatric Orthopaedic Surgery, New York (United States); Children' s Hospital Boston, Department of Orthopaedic Surgery, Boston, Massachusetts (United States)

    2005-09-01

    A 9-year-old girl with multiple osteochondromatosis presented with a 1 year history of a gradually enlarging surface lesion originating from the midsection of the right humerus, distal to an osteochondroma. Radiographically and histologically this lesion proved to be a periosteal chondrosarcoma adjacent to an osteochondroma. (orig.)

  8. The presentation, treatment and outcome of periosteal chondrosarcoma in the Netherlands

    NARCIS (Netherlands)

    Goedhart, L. M.; Ploegmakers, J. J. W.; Kroon, H. M.; Zwartkruis, E. C. H.; Jutte, P. C.

    In this case study, we describe the clinical presentation and treatment of 36 patients with periosteal chondrosarcoma collected over a 59-year period by the archive of the Netherlands Committee on Bone Tumours. The demographics, clinical presentation, radiological features, treatment and follow-up

  9. Mesenchymal chondrosarcoma of the orbit: CT and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Yang, B.T., E-mail: cjr.yangbentao@vip.163.com [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing (China); Wang, Y.Z.; Wang, X.Y.; Wang, Z.C. [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing (China)

    2012-04-15

    Aim: To describe the computed tomography (CT) and magnetic resonance imaging (MRI) features of orbital mesenchymal chondrosarcomas (MCSs). Materials and methods: Six patients with histology-confirmed MCSs of the orbit were retrospectively reviewed. All six patients underwent CT and MRI. Imaging studies were evaluated for the following: (a) tumour location, (b) configuration, size, and margin, (c) CT attenuation and MRI signal intensity, and (d) secondary manifestations. Additionally, the time-intensity curve (TIC) of dynamic contrast-enhanced (DCE) MRI were analysed in five patients. Results: Two MCSs arose in the right orbit and four in the left orbit. Five MCSs were located in the retrobulbar intraconal space and one in the extraconal space. All the lesions displayed a lobulate configuration and had a well-defined margin. The mean maximum diameter was 25.8 mm (range 15-36 mm). On unenhanced CT, the lesions appeared isodense to grey matter in six patients, with calcifications in five. Two patients showed inhomogeneous, moderate enhancement on enhanced CT. Six MCSs appeared isointense on T1-weighted imaging and heterogeneously isointense on T2-weighted imaging. The lesions showed significantly heterogeneous contrast enhancement. Five patients had DCE MRI and the TICs showed a rapidly enhancing and rapid washout pattern (type III). The following features were also detected: compression of the extra-ocular muscle (six patients, 100%); displacement of the optic nerve (five patients, 83.3%); and encasing globe (three patients, 50%). Conclusions: A well-defined, lobulate orbital mass with calcification on CT and, marked heterogeneous enhancement and type III TIC on MRI are highly suspicious of orbital MCSs.

  10. Cell cycle regulation in human embryonic stem cells: links to adaptation to cell culture.

    Science.gov (United States)

    Barta, Tomas; Dolezalova, Dasa; Holubcova, Zuzana; Hampl, Ales

    2013-03-01

    Cell cycle represents not only a tightly orchestrated mechanism of cell replication and cell division but it also plays an important role in regulation of cell fate decision. Particularly in the context of pluripotent stem cells or multipotent progenitor cells, regulation of cell fate decision is of paramount importance. It has been shown that human embryonic stem cells (hESCs) show unique cell cycle characteristics, such as short doubling time due to abbreviated G1 phase; these properties change with the onset of differentiation. This review summarizes the current understanding of cell cycle regulation in hESCs. We discuss cell cycle properties as well as regulatory machinery governing cell cycle progression of undifferentiated hESCs. Additionally, we provide evidence that long-term culture of hESCs is accompanied by changes in cell cycle properties as well as configuration of several cell cycle regulatory molecules.

  11. Cell Culture Assay for Human Noroviruses [response

    Energy Technology Data Exchange (ETDEWEB)

    Straub, Tim M.; Honer Zu Bentrup, Kerstin; Orosz Coghlan, Patricia; Dohnalkova, Alice; Mayer, Brooke K.; Bartholomew, Rachel A.; Valdez, Catherine O.; Bruckner-Lea, Cindy J.; Gerba, Charles P.; Abbaszadegan, Morteza A.; Nickerson, Cheryl A.

    2007-07-01

    We appreciate the comments provided by Leung et al., in response to our recently published article “In Vitro Cell Culture Infectivity Assay for Human Noroviruses” by Straub et al. (1). The specific aim of our project was to develop an in vitro cell culture infectivity assay for human noroviruses (hNoV) to enhance risk assessments when they are detected in water supplies. Reverse transcription (RT) qualitative or quantitative PCR are the primary assays for waterborne NoV monitoring. However, these assays cannot distinguish between infectious vs. non-infectious virions. When hNoV is detected in water supplies, information provided by our infectivity assay will significantly improve risk assessment models and protect human health, regardless of whether we are propagating NoV. Indeed, in vitro cell culture infectivity assays for the waterborne pathogen Cryptosporidium parvum that supplement approved fluorescent microscopy assays, do not result in amplification of the environmentally resistant hard-walled oocysts (2). However, identification of life cycle stages in cell culture provides evidence of infectious oocysts in a water supply. Nonetheless, Leung et al.’s assertion regarding the suitability of our method for the in vitro propagation of high titers of NoV is valid for the medical research community. In this case, well-characterized challenge pools of virus would be useful for developing and testing diagnostics, therapeutics, and vaccines. As further validation of our published findings, we have now optimized RT quantitative PCR to assess the level of viral production in cell culture, where we are indeed finding significant increases in viral titer. The magnitude and time course of these increases is dependent on both virus strain and multiplicity of infection. We are currently preparing a manuscript that will discuss these findings in greater detail, and the implications this may have for creating viral challenge pools

  12. Nicotinamide extends replicative lifespan of human cells.

    Science.gov (United States)

    Kang, Hyun Tae; Lee, Hyung Il; Hwang, Eun Seong

    2006-10-01

    We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.

  13. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

    Directory of Open Access Journals (Sweden)

    Hayato Fukusumi

    2016-01-01

    Full Text Available Human neural progenitor cells (hNPCs have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi. Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

  14. Immortalization of human myogenic progenitor cell clone retaining multipotentiality

    International Nuclear Information System (INIS)

    Hashimoto, Naohiro; Kiyono, Tohru; Wada, Michiko R.; Shimizu, Shirabe; Yasumoto, Shigeru; Inagawa, Masayo

    2006-01-01

    Human myogenic cells have limited ability to proliferate in culture. Although forced expression of telomerase can immortalize some cell types, telomerase alone delays senescence of human primary cultured myogenic cells, but fails to immortalize them. In contrast, constitutive expression of both telomerase and the E7 gene from human papillomavirus type 16 immortalizes primary human myogenic cells. We have established an immortalized primary human myogenic cell line preserving multipotentiality by ectopic expression of telomerase and E7. The immortalized human myogenic cells exhibit the phenotypic characteristics of their primary parent, including an ability to undergo myogenic, osteogenic, and adipogenic terminal differentiation under appropriate culture conditions. The immortalized cells will be useful for both basic and applied studies aimed at human muscle disorders. Furthermore, immortalization by transduction of telomerase and E7 represents a useful method by which to expand human myogenic cells in vitro without compromising their ability to differentiate

  15. Proteoglycans as Target for an Innovative Therapeutic Approach in Chondrosarcoma: Preclinical Proof of Concept.

    Science.gov (United States)

    Peyrode, Caroline; Weber, Valérie; Voissière, Aurélien; Maisonial-Besset, Aurélie; Vidal, Aurélien; Auzeloux, Philippe; Gaumet, Vincent; Borel, Michèle; Dauplat, Marie-Mélanie; Quintana, Mercedes; Degoul, Françoise; Rédini, Françoise; Chezal, Jean-Michel; Miot-Noirault, Elisabeth

    2016-11-01

    To date, surgery remains the only option for the treatment of chondrosarcoma, which is radio- and chemoresistant due in part to its large extracellular matrix (ECM) and poor vascularity. In case of unresectable locally advanced or metastatic diseases with a poor prognosis, improving the management of chondrosarcoma still remains a challenge. Our team developed an attractive approach of improvement of the therapeutic index of chemotherapy by targeting proteoglycan (PG)-rich tissues using a quaternary ammonium (QA) function conjugated to melphalan (Mel). First of all, we demonstrated the crucial role of the QA carrier for binding to aggrecan by surface plasmon resonance. In the orthotopic model of Swarm rat chondrosarcoma, an in vivo biodistribution study of Mel and its QA derivative (Mel-QA), radiolabeled with tritium, showed rapid radioactivity accumulation in healthy cartilaginous tissues and tumor after [ 3 H]-Mel-QA injection. The higher T/M ratio of the QA derivative suggests some advantage of QA-active targeting of chondrosarcoma. The antitumoral effects were characterized by tumor volume assessment, in vivo 99m Tc-NTP 15-5 scintigraphic imaging of PGs, 1 H-HRMAS NMR spectroscopy, and histology. The conjugation of a QA function to Mel did not hamper its in vivo efficiency and strongly improved the tolerability of Mel leading to a significant decrease of side effects (hematologic analyses and body weight monitoring). Thus, QA conjugation leads to a significant improvement of the therapeutic index, which is essential in oncology and enable repeated cycles of chemotherapy in patients with chondrosarcoma. Mol Cancer Ther; 15(11); 2575-85. ©2016 AACR. ©2016 American Association for Cancer Research.

  16. Management of tracheal chondrosarcoma almost completely obstructing the airway: a case report.

    Science.gov (United States)

    Andolfi, Marco; Vaccarili, Maurizio; Crisci, Roberto; Puma, Francesco

    2016-07-11

    Primary malignant tracheal tumors account for only 0.2 % of all malignancies of the respiratory tract. Tracheal chondrosarcoma is a rare condition and only 17 cases have been described in the literature from 1965 to date. Herein we report the very unusual case of a patient with a tracheal chondrosarcoma, electively treated by curative surgery despite the virtually complete obstruction of the airway. We present the case of a 79-year old Caucasian man with long-lasting wheezing misdiagnosed as asthma and affected by a tracheal chondrosarcoma almost completely obstructing the airway. Videobronchoscopy and imaging investigations revealed a well-circumscribed mass arising from the cartilaginous rings of the cervical trachea with a posterior residual respiratory space of about 1 mm. Because of the mobility and flaccidity of the uninvolved pars membranacea, the tiny respiratory space slightly expanded during inspiration and expiration allowing the patient to be treated without an essential emergency procedure. Standard tracheal intubation was impossible. Rigid bronchoscopy enabled placement of a small tracheal tube distally to the tumor. Successful cervical tracheal resection and reconstruction was then performed, achieving complete tumor excision. Histologically, the mass was characterized as a low-grade tracheal chondrosarcoma. Videobronchoscopy performed 9 months after surgery showed a wide, well healed tracheal anastomosis. Ten months after surgery, the patient is alive and disease free. Complete surgical resection is the treatment of choice for tracheal chondrosarcoma. Rigid bronchoscopy is an essential tool for diagnostic and therapeutic purposes. It allows the palliative maneuvers for obstruction relief but also, in resectable patients, the intraoperative safe and straightforward management of the obstructed airway.

  17. Functional and oncological outcome after surgical resection of the scapula and clavicle for primary chondrosarcoma.

    Science.gov (United States)

    Nota, S P F T; Russchen, M J A M; Raskin, K A; Mankin, H J; Hornicek, F J; Schwab, J H

    2017-04-01

    The scapula is a relatively common site for chondrosarcoma to develop in contrary to the clavicle, which is rarely affected by these tumors. The aim of this study is to determine the functional and oncological outcome for patients treated operatively for scapular or clavicular chondrosarcoma. In this single-center retrospective study, we included a sample of 20 patients that received the diagnosis of a primary chondrosarcoma of the scapula or clavicle. Of the surviving patients, the functional function was assessed using the DASH and the PROMIS Physical Function-Upper Extremity. Patients were longitudinally tracked for their oncological outcome. All patients were followed for at least 2 years or until death. The mean age of the cohort was 47 years. Eighteen patients suffered from a chondrosarcoma of the scapula, and in 2 patients, the tumor was located in the clavicle. Metastasis, local recurrence and a higher tumor grade were all associated with a decreased overall survival. For the patients with a chondrosarcoma of the scapula, the average DASH score was 16 ± 16 and the mean PROMIS Physical Function-Upper Extremity score was 48 ± 10. Patients with both an intact rotator cuff and glenoid had a better physical function. Upper extremity function after (partial) scapulectomy varied depending on whether the glenoid was spared and whether a functioning shoulder abductor remained. When the resection spared these structures, then excellent functional outcomes were reported. Oncologic outcomes depended upon the grade of the tumor and whether local recurrence and metastases occurred.

  18. Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells

    International Nuclear Information System (INIS)

    Perkel, V.S.; Mohan, S.; Herring, S.J.; Baylink, D.J.; Linkhart, T.A.

    1990-01-01

    Prostatic cancer typically produces osteoblastic metastases which are not attended by marrow fibrosis. In the present study we sought to test the hypothesis that prostatic cancer cells produce factor(s) which act selectively on human osteoblasts. Such a paracrine mechanism would explain the observed increase in osteoblasts, unaccompanied by an increase in marrow fibroblasts. To test this hypothesis we investigated the mitogenic activity released by the human prostatic tumor cell line, PC3. PC3 cells have been reported previously to produce mitogenic activity for cells that was relatively specific for rat osteoblasts compared to rat fibroblasts. However, the effects of this activity on human cells has not been examined previously. PC3-conditioned medium (CM) (5-50 micrograms CM protein/ml) stimulated human osteoblast proliferation by 200-950% yet did not stimulate human fibroblast proliferation ([3H]thymidine incorporation). PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures. To determine whether the osteoblast-specific mitogenic activity could be attributed to known bone growth factors, specific assays for these growth factors were performed. PC3 CM contained 10 pg insulin-like growth factor (IGF) I, less than 2 pg IGF II, 54 pg basic fibroblast growth factor, and 16 pg transforming growth factor beta/microgram CM protein. None of these growth factors alone or in combination could account for the observed osteoblast-specific PC3 cell-derived mitogenic activity. Furthermore, when 5 micrograms/ml PC3 CM was tested in combination with maximally effective concentrations of either basic fibroblast growth factor, IGF I, IGF II, or transforming growth factor beta, it produced an additive effect suggesting that PC3 CM stimulates osteoblast proliferation by a mechanism independent of these bone mitogens

  19. The role of EXT and growth signalling pathways in osteochondroma and its progression towards secondary peripheral chondrosarcoma

    NARCIS (Netherlands)

    Hameetman, Liesbeth

    2007-01-01

    Osteochondroma is a cartilage capped benign bone tumour, arising at the external surface of bones preformed by endochondral ossification. A small percentage of osteochondromas can progress towards its malignant counterpart, secondary peripheral chondrosarcoma. About 15% of osteochondromas occur in

  20. Differentiation of blood T cells: Reprogramming human induced pluripotent stem cells into neuronal cells

    Directory of Open Access Journals (Sweden)

    Ping-Hsing Tsai

    2015-06-01

    Conclusion: We have developed a safer method to generate integration-free and nonviral human iPSCs from adult somatic cells. This induction method will be useful for the derivation of human integration-free iPSCs and will also be applicable to the generation of iPSCs-derived neuronal cells for drug screening or therapeutics in the near future.

  1. Markers of T Cell Senescence in Humans

    Directory of Open Access Journals (Sweden)

    Weili Xu

    2017-08-01

    Full Text Available Many countries are facing the aging of their population, and many more will face a similar obstacle in the near future, which could be a burden to many healthcare systems. Increased susceptibility to infections, cardiovascular and neurodegenerative disease, cancer as well as reduced efficacy of vaccination are important matters for researchers in the field of aging. As older adults show higher prevalence for a variety of diseases, this also implies higher risk of complications, including nosocomial infections, slower recovery and sequels that may reduce the autonomy and overall quality of life of older adults. The age-related effects on the immune system termed as “immunosenescence” can be exemplified by the reported hypo-responsiveness to influenza vaccination of the elderly. T cells, which belong to the adaptive arm of the immune system, have been extensively studied and the knowledge gathered enables a better understanding of how the immune system may be affected after acute/chronic infections and how this matters in the long run. In this review, we will focus on T cells and discuss the surface and molecular markers that are associated with T cell senescence. We will also look at the implications that senescent T cells could have on human health and diseases. Finally, we will discuss the benefits of having these markers for investigators and the future work that is needed to advance the field of T cell senescence markers.

  2. Carbon ion radiotherapy for chordomas and low-grade chondrosarcomas of the skull base. Results in 67 patients

    Energy Technology Data Exchange (ETDEWEB)

    Schulz-Ertner, D.; Wannenmacher, M. [Dept. of Clinical Radiology, Univ. of Heidelberg (Germany); Nikoghosyan, A.; Thilmann, C.; Jaekel, O.; Karger, C. [German Cancer Research Center (dkfz), Heidelberg (Germany); Haberer, T.; Scholz, M.; Kraft, G. [Dept. of Biophysics, German Ion Research Center (GSI), Darmstadt (Germany); Debus, J. [Dept. of Clinical Radiology, Univ. of Heidelberg (Germany); German Cancer Research Center (dkfz), Heidelberg (Germany)

    2003-09-01

    Purpose: To prospectively evaluate outcome and toxicity after carbon ion radiotherapy (RT) in chordomas and low-grade chondrosarcomas. Patients and Methods: Between September 1998 and December 2001, 74 patients were treated for chordomas and chondrosarcomas with carbon ion RT at the ''Gesellschaft fuer Schwerionenforschung'' (GSI). Seven patients reirradiated with reduced carbon ion doses after conventional RT were excluded from the analysis, leaving 67 evaluable patients (44 chordomas and 23 chondrosarcomas) who received a full course of carbon ion therapy. Tumor-conform application of carbon ion beams was realized by intensity-controlled raster scanning with active energy variation. Three-dimensional treatment planning included intensity modulation and biological plan optimization. A median dose of 60 GyE was applied to the target volume within 20 consecutive days at a dose of 3.0 GyE per fraction. Results: Median follow-up was 15 months (range 3-46 months). At 3 years, actuarial local control was 100% for chondrosarcomas and 87% for chordomas, respectively. Partial tumor remission was observed in 14/44 (31%) chordoma patients and in 4/23 (17%) chondrosarcoma patients. At 3 years, actuarial overall survival was 100% for chondrosarcomas and 89% for chordomas, respectively. No severe side effects > CTC III have been observed. Conclusions: These data demonstrate the clinical efficiency and safety of scanning beam delivery of carbon ion beams in patients with skull base chordomas and chondrosarcomas. The observation of tumor regressions at a dose level of 60 GyE may indicate that the biological effectiveness of carbon ions in chordomas and chondrosarcomas is higher than initially estimated. (orig.)

  3. Carbon ion radiotherapy for chordomas and low-grade chondrosarcomas of the skull base. Results in 67 patients

    International Nuclear Information System (INIS)

    Schulz-Ertner, D.; Wannenmacher, M.; Nikoghosyan, A.; Thilmann, C.; Jaekel, O.; Karger, C.; Haberer, T.; Scholz, M.; Kraft, G.; Debus, J.

    2003-01-01

    Purpose: To prospectively evaluate outcome and toxicity after carbon ion radiotherapy (RT) in chordomas and low-grade chondrosarcomas. Patients and Methods: Between September 1998 and December 2001, 74 patients were treated for chordomas and chondrosarcomas with carbon ion RT at the ''Gesellschaft fuer Schwerionenforschung'' (GSI). Seven patients reirradiated with reduced carbon ion doses after conventional RT were excluded from the analysis, leaving 67 evaluable patients (44 chordomas and 23 chondrosarcomas) who received a full course of carbon ion therapy. Tumor-conform application of carbon ion beams was realized by intensity-controlled raster scanning with active energy variation. Three-dimensional treatment planning included intensity modulation and biological plan optimization. A median dose of 60 GyE was applied to the target volume within 20 consecutive days at a dose of 3.0 GyE per fraction. Results: Median follow-up was 15 months (range 3-46 months). At 3 years, actuarial local control was 100% for chondrosarcomas and 87% for chordomas, respectively. Partial tumor remission was observed in 14/44 (31%) chordoma patients and in 4/23 (17%) chondrosarcoma patients. At 3 years, actuarial overall survival was 100% for chondrosarcomas and 89% for chordomas, respectively. No severe side effects > CTC III have been observed. Conclusions: These data demonstrate the clinical efficiency and safety of scanning beam delivery of carbon ion beams in patients with skull base chordomas and chondrosarcomas. The observation of tumor regressions at a dose level of 60 GyE may indicate that the biological effectiveness of carbon ions in chordomas and chondrosarcomas is higher than initially estimated. (orig.)

  4. Elevated Levels of Dickkopf-1 Are Associated with β-Catenin Accumulation and Poor Prognosis in Patients with Chondrosarcoma

    Science.gov (United States)

    Chen, Changbao; Zhou, Hua; Zhang, Xiaolin; Ma, Xinlong; Liu, Zhongjun; Liu, Xiaoguang

    2014-01-01

    Background Dickkopf-1 (DKK1) is an antagonist of Wnt/β-catenin signaling implicated in tumorigenesis. However, the biological role of DKK1 and β-catenin involved in chondrosarcoma has not been sufficiently investigated. This study was designed to investigate the expression profiles of DKK1 and β-catenin, and to clarify their clinical values in chondrosarcoma. Methods The mRNA and protein levels of DKK1 and β-catenin in fresh chondrosarcoma and the corresponding non-tumor tissues were analyzed by Real-time PCR and Western blot, respectively. The protein expression patterns of DKK1 and β-catenin were investigated by immunohistochemistry. The associations among DKK1 level, β-catenin accumulation, clinicopathological factors and the overall survival were separately evaluated. Results Both DKK1 and β-catenin levels were remarkably elevated in chondrosarcoma compared with the corresponding non-tumor tissues. High DKK1 level and positive β-catenin accumulation in chondrosarcoma specimens were 58.7% and 53.9%, respectively. Elevated DKK1 level significantly correlated with positive β-catenin accumulation, and they were remarkably associated with histological grade and Musculoskeletal Tumor Society stage. Furthermore, DKK1 level and β-catenin accumulation had significant impacts on the prognosis of chondrosarcoma patients. Multivariate analysis revealed that DKK1 level was an independent prognostic factor for overall survival. Conclusions Elevated DKK1 levels associated with β-catenin accumulation play a crucial role in chondrosarcoma. DKK1 can serve as a novel predictor of poor prognosis in patients with chondrosarcoma. PMID:25144498

  5. Human embryonic stem cells and microenvironment

    Directory of Open Access Journals (Sweden)

    Banu İskender

    2014-09-01

    Full Text Available Human embryonic stem cells (hESCs possess a great potential in the field of regenerative medicine by their virtue of pluripotent potential with indefinite proliferation capabilities. They can self renew themselves and differentiate into three embryonic germ layers. Although they are conventionally grown on mitotically inactivated mouse feeder cells, there are in vitro culture systems utilizing feeder cells of human origin in order to prevent cross-species contamination. Recently established in vitro culture systems suggested that direct interaction with feeder cells is not necessary but rather attachment to a substrate is required to ensure long-term, efficient hESC culture in vitro. This substrate is usually composed of a mixture of extracellular matrix components representing in vivo natural niche. In hESC biology, the mechanism of interaction of hESCs with extracellular matrix molecules remained insufficiently explored area of research due to their transient nature of interaction with the in vivo niche. However, an in vitro culture system established using extracellular matrix molecules may provide a safer alternative to culture systems with feeder cells while paving the way to Good Manufacturing Practice-GMP production of hESCs for therapeutic purposes. Therefore, it is essential to study the interaction of extracellular matrix molecules with hESCs in order to standardize in vitro culture systems for large-scale production of hESCs in a less labor-intensive way. This would not only provide valuable information regarding the mechanisms that control pluripotency but also serve to dissect the molecular signaling pathways of directed differentiation for prospective therapeutic applications in the future. J Clin Exp Invest 2014; 5 (3: 486-495

  6. The Cultivation of Human Granulosa Cells

    Directory of Open Access Journals (Sweden)

    Lenka Brůčková

    2008-01-01

    Full Text Available The major functions of granulosa cells (GCs include the production of steroids, as well as a myriad of growth factors to interact with the oocyte during its development within the ovarian follicle. Also FSH stimulates GCs to convert androgens (coming from the thecal cells to estradiol by aromatase. However, after ovulation the GCs produce progesterone that may maintain a potential pregnancy. Experiments with human GCs are mainly focused on the purification of GCs from ovarian follicular fluid followed by FACS analysis or short-term cultivation. The aim of our study was to cultivate GCs for a long period, to characterize their morphology and phenotype. Moreover, we have cultivated GCs under gonadotropin stimulation in order to simulate different pathological mechanisms during folliculogenesis (e.g. ovarian hyperstimulation syndrome. GCs were harvested from women undergoing in vitro fertilization. Complex oocyte-cumulus oophorus was dissociated by hyaluronidase. The best condition for transport of GCs was optimized as short transport in follicular fluid at 37 °C. GCs expansion medium consisted of DMEM/F12, 2 % FCS, ascorbic acid, dexamethasone, L-glutamine, gentamycine, penicillin, streptomycin and growth factors (EGF, bFGF. GCs transported in follicular fluid and cultivated in 2 % FCS containing DMEM/F12 medium supplemented with follicular fluid presented increased adhesion, proliferation, viability and decreased doubling time. Cell viability was 92 % and mean cell doubling time was 52 hrs. We have optimized transport and cultivation protocols for long-term cultivation of GCs.

  7. Single Cell Dissection of Human Pancreatic Islet Dysfunction in Diabetes

    Science.gov (United States)

    2017-06-01

    of memory T cells , innate cells and the differentiation potential of naive T cells during ME/CFS; and 3) To determine the T cell and innate cell ...apoptosis and the innate immune response in human pancreatic β- cells . Diabetes 64: 3808–3817. Marselli L, Thorne J, Dahiya S, Sgroi DC, Sharma A, Bonner-Weir...interactive nature of CellView aids in cell doublet identification. In the PBMC data, ‘Subcluster-analysis’ reveals a mixture of lymphoid and myeloid

  8. Do Patients After Chondrosarcoma Treatment Have Age-appropriate Bone Mineral Density in the Long Term?

    Science.gov (United States)

    Hobusch, Gerhard M; Tiefenboeck, Thomas M; Patsch, Janina; Krall, Christoph; Holzer, Gerold

    2016-06-01

    In long-term survivors of osteosarcoma and Ewing sarcoma treated with the addition of radio- and chemotherapy, low bone mineral density (BMD) and fractures have been observed, presumably resulting from these adjuvants. Because patients with chondrosarcoma usually are not treated with conventional adjuvant treatment, observation of low BMD in patients with chondrosarcoma presumably would be the result of other mechanisms. However, BMD in patients with a history of chondrosarcoma has not been well characterized. The aim of our study was to address the following questions: (1) Do long-term survivors of chondrosarcoma have normal BMD and, if not, which factors contribute to low BMD? (2) Is there a greater risk of fracture and does the Fracture Risk Assessment Tool (FRAX(®)) score reflect fracture likelihood? All known patients with a history of chondrosarcoma treated at our institution before 2006 were identified. Of 127 patients believed to be alive at the time of this study, 30 agreed to participate in this study (11 females, 19 males; mean age at surgery, 39 ± 12 years; mean followup, 12 ± 5 years). With the data available, the 30 participants were not different from the 97 nonparticipants in terms of age, sex, BMI, tumor grade, tumor location (axial versus appendicular, lower extremity versus elsewhere), and use of any treatment known to influence osteopenia (chemotherapy, lower extremity surgery). BMD was measured and history of fractures was assessed using a questionnaire. The patients´ BMD measurements in this study were sex- and age-matched with a normative sex- and age-categorized reference population reported by Kudlacek et al. Associations were tested by univariate regressions and ANOVAs of all measures of BMD and eligible oncologic and demographic factors. Eighteen of 30 (60%) patients had a pathologic BMD according to the WHO dual-energy x-ray absorptiometry definition, 15 (50%) had osteopenia, and three (10%) had osteoporosis. T-scores in the

  9. Proteomic Analysis of Human Blastocoel Fluid and Blastocyst Cells

    DEFF Research Database (Denmark)

    Linnert Jensen, Pernille; Beck, Hans Christian; Petersen, Jørgen

    The human blastocyst consists of 100-200 cells that are organized in an outer layer of differentiated trophectoderm (TE) cells lining the blastocyst cavity into which the undifferentiated inner cell mass (ICM) protrudes. The cavity of the blastocyst is filled with blastocoel fluid to which all...... the cells of the blastocyst are exposed. The ICM is the starting point for the development of undifferentiated human embryonic stem cells (hESCs), which posses the potential to develop into any cell type present in the adult human body [1,2]. This ability makes hESCs a potential source of cells...

  10. Studies in human skin epithelial cell carcinogenesis

    International Nuclear Information System (INIS)

    Lehman, T.A.

    1987-01-01

    Metabolism and DNA adduct formation of benzo[a]pyrene (BP) by human epidermal keratinocytes pretreated with inhibitors or inducer of cytochrame P450 was studied. To study DNA adduct analysis, cultures were pretreated as described above, and then treated with non-radiolabeled BP. DNA was prepared from these cultures, digested to the nucleotide level, and 32 P-postlabeled for adduct analysis. Cultures pretreated with BHA, 7,8-BF or disulfiralm formed significantly fewer BPDE I-dB adducts than non-pretreated cultures, while cultures pretreated with MeBHA formed more BPDE-I-dG adducts. MeBHA increased BP activation and adduct formation inhuman keratinocyte in cultures by inducing a specific isoenzyme of cytochrome P450 which preferentially increases the oxidative metabolism of BP to 7,8 diol BP and 7,8 diol BP to BPDE I. To approximate an in vivo human system, metabolism of BPDE I by human skin xenografts treated with cell cycles modulators was studied. When treated with BPDE I, specific carcinogen-DNA adducts were formed. Separation and identification of these adducts by the 32 P-postlabeling technique indicated that the 7R- and 7S-BPDE I-dG adducts were the major adducts

  11. Technical Challenges in the Derivation of Human Pluripotent Cells

    Directory of Open Access Journals (Sweden)

    Parinya Noisa

    2011-01-01

    Full Text Available It has long been discovered that human pluripotent cells could be isolated from the blastocyst state of embryos and called human embryonic stem cells (ESCs. These cells can be adapted and propagated indefinitely in culture in an undifferentiated manner as well as differentiated into cell representing the three major germ layers: endoderm, mesoderm, and ectoderm. However, the derivation of human pluripotent cells from donated embryos is limited and restricted by ethical concerns. Therefore, various approaches have been explored and proved their success. Human pluripotent cells can also be derived experimentally by the nuclear reprogramming of somatic cells. These techniques include somatic cell nuclear transfer (SCNT, cell fusion and overexpression of pluripotent genes. In this paper, we discuss the technical challenges of these approaches for nuclear reprogramming, involving their advantages and limitations. We will also highlight the possible applications of these techniques in the study of stem cell biology.

  12. Stereological quantification of mast cells in human synovium

    DEFF Research Database (Denmark)

    Damsgaard, T E; Sørensen, Flemming Brandt; Herlin, T

    1999-01-01

    Mast cells participate in both the acute allergic reaction as well as in chronic inflammatory diseases. Earlier studies have revealed divergent results regarding the quantification of mast cells in the human synovium. The aim of the present study was therefore to quantify these cells in the human...... synovium, using stereological techniques. Different methods of staining and quantification have previously been used for mast cell quantification in human synovium. Stereological techniques provide precise and unbiased information on the number of cell profiles in two-dimensional tissue sections of......, in this case, human synovium. In 10 patients suffering from osteoarthritis a median of 3.6 mast cells/mm2 synovial membrane was found. The total number of cells (synoviocytes, fibroblasts, lymphocytes, leukocytes) present was 395.9 cells/mm2 (median). The mast cells constituted 0.8% of all the cell profiles...

  13. A Chemical Probe that Labels Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Nao Hirata

    2014-03-01

    Full Text Available A small-molecule fluorescent probe specific for human pluripotent stem cells would serve as a useful tool for basic cell biology research and stem cell therapy. Screening of fluorescent chemical libraries with human induced pluripotent stem cells (iPSCs and subsequent evaluation of hit molecules identified a fluorescent compound (Kyoto probe 1 [KP-1] that selectively labels human pluripotent stem cells. Our analyses indicated that the selectivity results primarily from a distinct expression pattern of ABC transporters in human pluripotent stem cells and from the transporter selectivity of KP-1. Expression of ABCB1 (MDR1 and ABCG2 (BCRP, both of which cause the efflux of KP-1, is repressed in human pluripotent stem cells. Although KP-1, like other pluripotent markers, is not absolutely specific for pluripotent stem cells, the identified chemical probe may be used in conjunction with other reagents.

  14. Alternative Sources of Adult Stem Cells: Human Amniotic Membrane

    Science.gov (United States)

    Wolbank, Susanne; van Griensven, Martijn; Grillari-Voglauer, Regina; Peterbauer-Scherb, Anja

    Human amniotic membrane is a highly promising cell source for tissue engineering. The cells thereof, human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC), may be immunoprivileged, they represent an early developmental status, and their application is ethically uncontroversial. Cell banking strategies may use freshly isolated cells or involve in vitro expansion to increase cell numbers. Therefore, we have thoroughly characterized the effect of in vitro cultivation on both phenotype and differentiation potential of hAEC. Moreover, we present different strategies to improve expansion including replacement of animal-derived supplements by human platelet products or the introduction of the catalytic subunit of human telomerase to extend the in vitro lifespan of amniotic cells. Characterization of the resulting cultures includes phenotype, growth characteristics, and differentiation potential, as well as immunogenic and immunomodulatory properties.

  15. In Vitro Cardiomyogenic Potential of Human Amniotic Fluid Stem Cells

    OpenAIRE

    Guan, Xuan; Delo, Dawn M.; Atala, Anthony; Soker, Shay

    2011-01-01

    Stem cell therapy for damaged cardiac tissue is currently limited by a number of factors, including the inability to obtain sufficient cell numbers, the potential tumorigenicity of certain types of stem cells, and the possible link between stem cell therapy and the development of malignant arrhythmias. In this study, we investigated whether human amniotic fluid-derived stem (hAFS) cells could be a potential source of cells for cardiac cell therapy by testing the in vitro differentiation capab...

  16. Trichloroethylene toxicity in a human hepatoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Thevenin, E.; McMillian, J. [Medical Univ. of Charleston South Carolina, SC (United States)

    1994-12-31

    The experiments conducted in this study were designed to determine the usefullness of hepatocyte cultures and a human hepatoma cell line as model systems for assessing human susceptibility to hepatocellular carcinoma due to exposure to trichloroethylene. The results from these studies will then be analyzed to determine if human cell lines can be used to conduct future experiments of this nature.

  17. Identification of human tissue cross-presenting dendritic cells

    OpenAIRE

    Haniffa, Muzlifah; Collin, Matthew; Ginhoux, Florent

    2013-01-01

    Dendritic cells (DCs) are a heterogeneous group of functionally specialized antigen-presenting cells. We recently characterized the human tissue cross-presenting DCs and aligned the human and mouse DC subsets. Our findings will facilitate the translation of murine DC studies to the human setting and aid the design of DC-based vaccine strategies for infection and cancer immunotherapy.

  18. Primary chondrosarcoma of breast - cytology with histopathological correlation: A rare case report with review of literature

    Directory of Open Access Journals (Sweden)

    Sankappa P. Sinhasan

    2014-01-01

    Full Text Available Malignant mesenchymal tumors of the breast other than angiosarcoma are extremely rare and comprise <0.5% of breast tumors. Primary chondrosarcoma of the breast is an extremely rare entity and only 10 cases are reported as single case reports in literature until date. A diagnosis of primary mammary sarcoma can be established only after excluding metaplastic carcinomas and malignant phyllodes by extensive sampling for evidence of in situ or invasive carcinoma. Here, we report a primary chondrosarcoma of breast in a 55-year-old lady diagnosed precisely on fine-needle aspiration cytology and confirmed by histopatholigcal examination after total mastectomy. We emphasize on diagnostic difficulties encountered in cytology smears and discuss differential diagnoses.

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

    Directory of Open Access Journals (Sweden)

    Surbhi Goyal

    2012-01-01

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

  20. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  1. MODERATE CYTOTOXICITY OF PROANTHOCYANIDINS TO HUMAN TUMOR-CELL LINES

    NARCIS (Netherlands)

    KOLODZIEJ, H; HABERLAND, C; WOERDENBAG, HJ; KONINGS, AWT

    In the present study the cytotoxicity of 16 proanthocyanidins was evaluated in GLC(4), a human small cell lung carcinoma cell line, and in COLO 320, a human colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. With IC50 values ranging from 18 to >200 mu m following continuous

  2. Isolation and in vitro expansion of human colonic stem cells

    NARCIS (Netherlands)

    Jung, P.; Sato, T.; Merlos-Suarez, A.; Barriga, F.M.; Iglesias, M.; Rossell, D.; Auer, H.; Gallardo, M.; Blasco, M.A.; Sancho, E.; Clevers, H.; Batlle, E.

    2011-01-01

    Here we describe the isolation of stem cells of the human colonic epithelium. Differential cell surface abundance of ephrin type-B receptor 2 (EPHB2) allows the purification of different cell types from human colon mucosa biopsies. The highest EPHB2 surface levels correspond to epithelial colonic

  3. The development of human mast cells. An historical reappraisal

    International Nuclear Information System (INIS)

    Ribatti, Domenico

    2016-01-01

    The understanding of mast cell (MC) differentiation is derived mainly from in vitro studies of different stages of stem and progenitor cells. The hematopoietic lineage development of human MCs is unique compared to other myeloid-derived cells. Human MCs originate from CD34"+/CD117"+/CD13"+multipotent hematopoietic progenitors, which undergo transendothelial recruitment into peripheral tissues, where they complete differentiation. Stem cell factor (SCF) is a major chemotactic factor for MCs and their progenitors. SCF also elicits cell-cell and cell-substratum adhesion, facilitates the proliferation, and sustains the survival, differentiation, and maturation, of MCs. Because MC maturation is influenced by local microenvironmental factors, different MC phenotypes can develop in different tissues and organs. - Highlights: • Human mast cells originate from CD34/CD117/CD13 positive multipotent hematopoietic progenitors. • Stem cell factor is a major chemotactic factor for mast cells and their progenitors. • Different mast cell phenotypes can develop in different tissues and organs.

  4. Low-grade chondrosarcoma of the cricoid cartilage: a case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Chuan-Ping; Liu, Ji-Hua; Xu, Wen-Jian [The Affiliated Hospital of Qingdao University, Department of Radiology, Qingdao (China); Hou, Feng [The Affiliated Hospital of Qingdao University, Department of Pathology, Qingdao (China); Liu, Hua [The Shinanqu People Hospital, Department of Radiology, Qingdao (China)

    2017-11-15

    We report the case of a 60-year-old man with a 12-day history of vomiting whenever he had a meal. Computed tomography revealed a calcified mass in the right cricoid cartilage with intraluminal and extraluminal extension. The patient underwent surgical resection of the trachea with end-to-end anastomosis. Pathological examination of the surgical specimen showed a low-grade chondrosarcoma. Eighteen months after surgery, the patient is alive and disease-free. (orig.)

  5. The role of radiosurgery in the management of chordoma and chondrosarcoma of the cranial base

    International Nuclear Information System (INIS)

    Kondziolka, D.; Lunsford, L.D.; Flickinger, J.C.

    1991-01-01

    Despite conventional multimodality treatment (surgery and fractionated radiation therapy), recurrence and clinical progression of cranial base chordomas and chondrosarcomas are common. The malignant behavior of these tumors is a result of their critical location, locally aggressive nature, and high recurrence rate. To explore the role of radiosurgery in the treatment of these skull base neoplasms, we assessed its use in four patients with chordoma and two with chondrosarcoma. In five of the patients, radiosurgery was used as adjuvant therapy for residual or recurrent tumors after surgical debulking, and in one patient with a chordoma, it was the primary treatment. No patient received fractionated external beam radiotherapy. All tumors were less than 30 mm in diameter and were treated with 20 Gy to the tumor margin. Skull base computed tomography and magnetic resonance images were essential to define the anatomic relationships between tumor and adjacent basal structures. During follow-up (mean, 22 mo; range, 8-36 mo), the authors found no progression of the treated tumor volume in any patient. Neurological deficits before treatment improved in three patients; the other three patients remained in stable neurological condition. Serial follow-up imaging studies demonstrated that two patients showed reduction in tumor size and four patients had no tumor growth. In one patient, a metastatic parietal lobe chondrosarcoma developed and was treated by microsurgery. Another patient showed tumor progression outside of the radiosurgical treatment volume. The authors results attest to the value of stereotactic radiosurgery as an adjuvant or primary treatment for selected patients with chordoma or chondrosarcoma and demonstrate its potential advantages over standard fractionated irradiation. Analysis of the long-term clinical and imaging effects after radiosurgery is warranted

  6. Differentiating high-grade from low-grade chondrosarcoma with MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hye Jin; Hong, Sung Hwan; Choi, Ja-Young; Choi, Jung-Ah; Kang, Heung Sik [Seoul National University College of Medicine, Department of Radiology and Institute of Radiation Medicine, Seoul (Korea); Moon, Kyung Chul [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea); Kim, Han-Soo [Seoul National University College of Medicine, Department of Orthopedic Surgery, Seoul (Korea)

    2009-12-15

    The purpose of the study was to evaluate the MR imaging features that differentiate between low-grade chondrosarcoma (LGCS) and high-grade chondrosarcoma (HGCS) and to determine the most reliable predictors for differentiation. MR images of 42 pathologically proven chondrosarcomas (28 LGCS and 14 HGCS) were retrospectively reviewed. There were 13 male and 29 female patients with an age range of 23-72 years (average age 51 years). On MR images, signal intensity, specific morphological characteristics including entrapped fat, internal lobular architecture, and outer lobular margin, soft tissue mass formation and contrast enhancement pattern were analysed. MR imaging features used to identify LGCS and HGCS were compared using univariate analysis and multivariate stepwise logistic regression analysis. On T1-weighted images, a central area of high signal intensity, which was not seen in LGCS, was frequently observed in HGCS (n = 5, 36%) (p < 0.01). Entrapped fat within the tumour was commonly seen in LGCS (n = 26, 93%), but not in HGCS (n = 1, 4%) (p < 0.01). LGCS more commonly (n = 24, 86%) preserved the characteristic internal lobular structures within the tumour than HGCSs (n = 4, 29%) (p < 0.01). Soft tissue formation was more frequently observed in HGCS (n = 11, 79%) than in LGCS (n = 1, 4%) (p < 0.01). On gadolinium-enhanced images, large central nonenhancing areas were exhibited in only two (7.1%) of LGCS, while HGCS frequently (n = 9, 64%) had a central nonenhancing portion (p < 0.01). Results of multivariate stepwise logistic regression analysis showed that soft tissue formation and entrapped fat within the tumour were the variables that could be used to independently differentiate LGCS from HGCS. There were several MR imaging features of chondrosarcoma that could be helpful in distinguishing HGCS from LGCS. Among them, soft tissue mass formation favoured the diagnosis of HGCS, and entrapped fat within the tumour was highly indicative of LGCS. (orig.)

  7. Differentiating high-grade from low-grade chondrosarcoma with MR imaging

    International Nuclear Information System (INIS)

    Yoo, Hye Jin; Hong, Sung Hwan; Choi, Ja-Young; Choi, Jung-Ah; Kang, Heung Sik; Moon, Kyung Chul; Kim, Han-Soo

    2009-01-01

    The purpose of the study was to evaluate the MR imaging features that differentiate between low-grade chondrosarcoma (LGCS) and high-grade chondrosarcoma (HGCS) and to determine the most reliable predictors for differentiation. MR images of 42 pathologically proven chondrosarcomas (28 LGCS and 14 HGCS) were retrospectively reviewed. There were 13 male and 29 female patients with an age range of 23-72 years (average age 51 years). On MR images, signal intensity, specific morphological characteristics including entrapped fat, internal lobular architecture, and outer lobular margin, soft tissue mass formation and contrast enhancement pattern were analysed. MR imaging features used to identify LGCS and HGCS were compared using univariate analysis and multivariate stepwise logistic regression analysis. On T1-weighted images, a central area of high signal intensity, which was not seen in LGCS, was frequently observed in HGCS (n = 5, 36%) (p < 0.01). Entrapped fat within the tumour was commonly seen in LGCS (n = 26, 93%), but not in HGCS (n = 1, 4%) (p < 0.01). LGCS more commonly (n = 24, 86%) preserved the characteristic internal lobular structures within the tumour than HGCSs (n = 4, 29%) (p < 0.01). Soft tissue formation was more frequently observed in HGCS (n = 11, 79%) than in LGCS (n = 1, 4%) (p < 0.01). On gadolinium-enhanced images, large central nonenhancing areas were exhibited in only two (7.1%) of LGCS, while HGCS frequently (n = 9, 64%) had a central nonenhancing portion (p < 0.01). Results of multivariate stepwise logistic regression analysis showed that soft tissue formation and entrapped fat within the tumour were the variables that could be used to independently differentiate LGCS from HGCS. There were several MR imaging features of chondrosarcoma that could be helpful in distinguishing HGCS from LGCS. Among them, soft tissue mass formation favoured the diagnosis of HGCS, and entrapped fat within the tumour was highly indicative of LGCS. (orig.)

  8. FDG PET imaging for grading and prediction of outcome in chondrosarcoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, Winfried; Eary, Janet F. [Division of Nuclear Medicine, University of Washington Medical Center, 1959 NE Pacific Street, Box 356113, WA 98195-6113, Seattle (United States); Conrad, Ernest U. [Department of Orthopaedics, University of Washington Medical Center, Seattle, WA (United States)

    2004-02-01

    The aims of this study were to assess the potential of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) for tumor grading in chondrosarcoma patients and to evaluate the role of standardized uptake value (SUV) as a parameter for prediction of patient outcome. FDG PET imaging was performed in 31 patients with chondrosarcoma prior to therapy. SUV was calculated for each tumor and correlated to tumor grade and size, and to patient outcome in terms of local relapse or metastatic disease with a mean follow-up period of 48 months. Chondrosarcomas were detectable in all patients. Tumor SUV was 3.38{+-}1.61 for grade I (n=15), 5.44{+-}3.06 for grade II (n=13), and 7.10{+-}2.61 for grade III (n=3). Significant differences were found between patients with and without disease progression: SUV was 6.42{+-}2.70 (n=10) in patients developing recurrent or metastatic disease compared with 3.74{+-}2.22 in patients without relapse (P=0.015). Using a cut-off of 4 for SUV, sensitivity, specificity, and positive and negative predictive values for a relapse were 90%, 76%, 64%, and 94%, respectively. Combining tumor grade and SUV, these parameters improved to 90%, 95%, 90%, and 95%, respectively. Pretherapeutic tumor SUV obtained by FDG PET imaging was a useful parameter for tumor grading and prediction of outcome in chondrosarcoma patients. The combination of SUV and histopathologic tumor grade further improved prediction of outcome substantially, allowing identification of patients at high risk for local relapse or metastatic disease. (orig.)

  9. Mesenchymal Chondrosarcoma of Maxilla: A Rare Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    R Thriveni

    2010-01-01

    Full Text Available Mesenchymal condrosarcomas are rare malignant neoplasms that can arise from both soft and hard tissues. They are distinct tumors arising in unicentric or multicentric locations. They reveal unusual clinical behavior, characteristic histopathological features, and poor prognosis with late recurrences. Here is a case report of a rare case of mesenchymal chondrosarcoma arising in a 19-year-old female patient′s right maxilla.

  10. Rare Case of a Chondrosarcoma of the Mandible in a Child

    Directory of Open Access Journals (Sweden)

    Hendryk Vieweg

    2013-01-01

    Full Text Available Chondrosarcoma of the mandible is rare, especially in children. The available literature consists mostly of a few case reports which are partly integrated in small studies. Growing this small pool of literature is helpful in solidifying knowledge about this disease and facilitating appropriate treatment for children. Therefore, we present such a case in a 12-year-old boy, exhibit comprehensive and relevant information concerning this entity, and discuss our findings in the context of other publications.

  11. Quaternary ammonium as vector of radioisotopes toward cartilage proteoglycans: in vivo imaging and monitoring of chondrosarcoma

    International Nuclear Information System (INIS)

    Peyrode, C.; Weber, V.; Vidal, A.; Auzeloux, P.; Besse, S.; Chezal, J.M.; Miot-Noirault, E.; Dauplat, M.M.; Gouin, F.; Redini, F.

    2013-01-01

    The full text of the publication follows. AIM: Our strategy consists in using the quaternary ammonium function, that exhibits a high affinity for proteoglycans, as a selective carrier to cartilage of (i) drugs for improving the selectivity or (ii) radioisotopes for imaging and evaluating response to treatment. For diagnosis, a radiotracer radiolabeled with 99m Tc ( 99m Tc-NTP 15-5) was selected and for therapeutic application, a quaternary ammonium derivative of melphalan (Mel-AQ) was synthesized. This study demonstrates the interest of this strategy for the diagnosis and treatment of chondrosarcoma. Methods: 99m Tc-NTP 15-5 imaging was performed at regular intervals in rats bearing ortho-topic swarm chondrosarcoma, controls or treated (Mel-AQ: three intravenous doses of 10 mg/kg). 99m Tc-HMDP imaging (the only radiotracer available for nuclear medicine diagnosis of chondrosarcoma) was also performed. Results: All rats exhibited a significant tumoral uptake of 99m Tc-NTP 15-5 at very early stage of pathology while no palpable nor measurable tumour could be assessed. Furthermore, tumoral uptake increased as pathology progressed over time. When animals were treated with Mel-AQ, a significant tumor growth inhibition was observed with 99m Tc-NTP 15-5 tumoral uptake being significantly decreased as compared to controls. 99m Tc-HMDP bone scans were negative during the whole study. Conclusion: These experimental results underline (i) the potential of the proteoglycan targeting strategy for the early and specific diagnosis imaging of chondrosarcoma and its response to therapy and (ii) the efficiency of the targeted anti-tumoral therapy. In future, we could plan to substitute technetium atom for copper atom for radionuclide therapy application. Grants: INCa, CPER, Ligue contre le cancer, FRI/OSEO. (authors)

  12. Intralesional curettage of central low-grade chondrosarcoma: A midterm follow-up study.

    Science.gov (United States)

    Chen, Yi-Chou; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Wei-Ming

    2017-03-01

    The aim of this study was to review the experience of surgical treatment of low-grade chondrosarcoma and to assess the long-term oncological and functional outcomes between intralesional curettage and wide excision. We included 11 patients with central low-grade chondrosarcoma lesions treated with intralesional curettage or wide excision from 1998 to 2013. Seven patients were treated with intralesional curettage and local adjuvant treatment (Group A), and four patients were treated with wide excision and reconstructive surgery (Group B). The mean age of patients was 43.8±17.6 years (range, 20-71 years), and the mean duration of follow-up was 84.4±47.6 months (range, 48-194 months). Group A had a significantly lower complication rate than Group B; three complications were documented in Group B (0% vs. 75%, p=0.024). The operative time (177.1 hours vs. 366.3 hours, p=0.010) and the hospital stay (6.6 days vs. 12.5 days, p=0.010) were significantly shorter in Group A. There was one local recurrence in Group A without statistical significance. Also, there were no differences between intralesional curettage and wide excision with respect to the blood loss. No metastasis disease occurred in either group during the follow-up period. The Musculoskeletal Tumor Society (MSTS) scores in Groups A and B were 99.0±2.5 and 94.2±4.2, respectively, with statistically significant difference (p=0.048). Extended intralesional curettage has the benefits of good MSTS score, shorter operative time, shorter hospital stay, and lower complication rate without increasing local recurrence in central low-grade chondrosarcoma. For central low-grade chondrosarcoma, we suggest extended curettage to decrease soft tissue damage and surgical risk. Copyright © 2016. Published by Elsevier Taiwan LLC.

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

    Science.gov (United States)

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

    2010-02-01

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

  14. The commitment of human cells to senescence.

    Science.gov (United States)

    Holliday, Robin

    2014-01-01

    Fifty years ago, it was demonstrated by Leonard Hayflick that human diploid fibroblasts grown in culture have a finite lifespan. Since that time, innumerable experiments have been published to discover the mechanism(s) that are responsible for this 'Hayflick limit' to continuous growth. Much new information has been gained, but there are certain features of this experimental system which have not been fully understood. One is the fact that different populations of the foetal lung strains WI-38 and MRC-5 have a range in division potential of at least a millionfold. The commitment theory of cellular aging, published more than 30 years ago, is able to explain this, but it has been consistently ignored. The theory predicts that bottlenecks, which are transient reductions in population size, can significantly reduce lifespan, or increase variability of lifespans. Computer simulations specify the effects of bottlenecks on longevity, and these were confirmed in two series of experiments. Commitment to senescence may be the loss of telomerase, which leads to the erosion of telomeres and the inability to grow indefinitely. Many experiments have been done with skin fibroblasts from human donors of different age, and it was originally thought that in vitro lifespan was inversely correlated with donor age. In these experiments, a single skin biopsy produces a population of cells that are grown to senescence. However, there is no reason to believe that skin fibroblasts are less variable in their in vitro lifespan than foetal lung strains, in which case the data points with skin cells are so variable that they may completely obscure any inverse correlation between culture lifespans and donor age.

  15. Oncologic outcome after local recurrence of chondrosarcoma: Analysis of prognostic factors.

    Science.gov (United States)

    Kim, Han-Soo; Bindiganavile, Srimanth S; Han, Ilkyu

    2015-06-01

    Literature on outcome after local recurrence (LR) in chondrosarcoma is scarce and better appreciation of prognostic factors is needed. (1) To evaluate post-LR oncologic outcomes of disease-specific survival and subsequent LR and (2) to identify prognostic factors for post-LR oncologic outcomes. Review of 28 patients with locally recurrent chondrosarcoma from the original cohort of 150 patients, who were treated surgically with or without adjuvants between 1982 and 2011, was performed. Mean age was 46 years (range, 21-73) which included 20 males and 8 females with mean follow up of 8.4 ± 7.5 years (range, 1.2-31.0). Post-LR survival at 5 years was 58.6 ± 10.3%. Age greater than 50 years (P = 0.011) and LR occurring within 1 year of primary surgery (P = 0.011) independently predicted poor survival. Seven patients suffered subsequent LR, which was significantly affected by surgical margin for LR (P = 0.038). Long-term survival of locally recurrent chondrosarcoma is achievable in a substantial number of patients. Older age at onset of LR and shorter interval from primary surgery to LR identifies high risk patients for poor post-LR survival while, wide surgical margins at LR surgery reduces the risk of subsequent LR. © 2015 Wiley Periodicals, Inc.

  16. Human Stem Cell Derived Cardiomyocytes: An Alternative ...

    Science.gov (United States)

    Chemical spills and associated deaths in the US has increased 2.6-fold and 16-fold from 1983 to 2012, respectfully. In addition, the number of chemicals to which humans are exposed to in the environment has increased almost 10-fold from 2001 to 2013 within the US. Internationally, a WHO report on the global composite impact of chemicals on health reported that 16% of the total burden of cardiovascular disease was attributed to environmental chemical exposure with 2.5 million deaths per year. Clearly, the cardiovascular system, at all its various developmental and life stages, represents a critical target organ system that can be adversely affected by existing and emerging chemicals (e.g., engineered nanomaterials) in a variety of environmental media. The ability to assess chemical cardiac risk and safety is critically needed but extremely challenging due to the number and categories of chemicals in commerce, as indicated. This presentation\\session will evaluate the use of adult human stem cell derived cardiomyocytes, and existing platforms, as an alternative model to evaluate environmental chemical cardiac toxicity as well as provide key information for the development of predictive adverse outcomes pathways associated with environmental chemical exposures. (This abstract does not represent EPA policy) Rapid and translatable chemical safety screening models for cardiotoxicity current status for informing regulatory decisions, a workshop sponsored by the Society

  17. Efficient and Fast Differentiation of Human Neural Stem Cells from Human Embryonic Stem Cells for Cell Therapy

    Directory of Open Access Journals (Sweden)

    Xinxin Han

    2017-01-01

    Full Text Available Stem cell-based therapies have been used for repairing damaged brain tissue and helping functional recovery after brain injury. Aberrance neurogenesis is related with brain injury, and multipotential neural stem cells from human embryonic stem (hES cells provide a great promise for cell replacement therapies. Optimized protocols for neural differentiation are necessary to produce functional human neural stem cells (hNSCs for cell therapy. However, the qualified procedure is scarce and detailed features of hNSCs originated from hES cells are still unclear. In this study, we developed a method to obtain hNSCs from hES cells, by which we could harvest abundant hNSCs in a relatively short time. Then, we examined the expression of pluripotent and multipotent marker genes through immunostaining and confirmed differentiation potential of the differentiated hNSCs. Furthermore, we analyzed the mitotic activity of these hNSCs. In this report, we provided comprehensive features of hNSCs and delivered the knowledge about how to obtain more high-quality hNSCs from hES cells which may help to accelerate the NSC-based therapies in brain injury treatment.

  18. New frontiers in human cell biology and medicine: can pluripotent stem cells deliver?

    Science.gov (United States)

    Goldstein, Lawrence S B

    2012-11-12

    Human pluripotent stem cells provide enormous opportunities to treat disease using cell therapy. But human stem cells can also drive biomedical and cell biological discoveries in a human model system, which can be directly linked to understanding disease or developing new therapies. Finally, rigorous scientific studies of these cells can and should inform the many science and medical policy issues that confront the translation of these technologies to medicine. In this paper, I discuss these issues using amyotrophic lateral sclerosis as an example.

  19. Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

    Directory of Open Access Journals (Sweden)

    Yajing Huang

    2016-01-01

    Full Text Available Trophoblast cell dysfunction is involved in many disorders during pregnancy such as preeclampsia and intrauterine growth restriction. Few treatments exist, however, that target improving trophoblast cell function. Human umbilical cord mesenchymal stem cells (hUCMSCs are capable of self-renewing, can undergo multilineage differentiation, and have homing abilities; in addition, they have immunomodulatory effects and paracrine properties and thus are a prospective source for cell therapy. To identify whether hUCMSCs can regulate trophoblast cell functions, we treated trophoblast cells with hUCMSC supernatant or cocultured them with hUCMSCs. Both treatments remarkably enhanced the migration and invasion abilities of trophoblast cells and upregulated their proliferation ability. At a certain concentration, hUCMSCs also modulated hCG, PIGF, and sEndoglin levels in the trophoblast culture medium. Thus, hUCMSCs have a positive effect on trophoblast cellular functions, which may provide a new avenue for treatment of placenta-related diseases during pregnancy.

  20. CD56 marks human dendritic cell subsets with cytotoxic potential

    NARCIS (Netherlands)

    Roothans, D.; Smits, E.; Lion, E.; Tel, J.; Anguille, S.

    2013-01-01

    Human plasmacytoid and myeloid dendritic cells (DCs), when appropriately stimulated, can express the archetypal natural killer (NK)-cell surface marker CD56. In addition to classical DC functions, CD56(+) DCs are endowed with an unconventional cytotoxic capacity.

  1. Bacteria, fungi, and viruses outnumber human cells 10:1

    Indian Academy of Sciences (India)

    Karen Nelson

    Fig 2. The distribution of the number of human cells by cell type. Sender R ... Type 2 diabetes ... Development of new predictive biomarkers so that preventive ... Microbiome, irrespective of lifestyle and age, which is distinct from races and.

  2. Microspectroscopy of spectral biomarkers associated with human corneal stem cells

    OpenAIRE

    Nakamura, Takahiro; Kelly, Jemma G.; Trevisan, J?lio; Cooper, Leanne J.; Bentley, Adam J.; Carmichael, Paul L.; Scott, Andrew D.; Cotte, Marine; Susini, Jean; Martin-Hirsch, Pierre L.; Kinoshita, Shigeru; Fullwood, Nigel J.; Martin, Francis L.

    2010-01-01

    Purpose Synchrotron-based radiation (SRS) Fourier-transform infrared (FTIR) microspectroscopy potentially provides novel biomarkers of the cell differentiation process. Because such imaging gives a ?biochemical-cell fingerprint? through a cell-sized aperture, we set out to determine whether distinguishing chemical entities associated with putative stem cells (SCs), transit-amplifying (TA) cells, or terminally-differentiated (TD) cells could be identified in human corneal epithelium. Methods D...

  3. Intestinal Stem Cell Dynamics: A Story of Mice and Humans.

    Science.gov (United States)

    Hodder, Michael C; Flanagan, Dustin J; Sansom, Owen J

    2018-06-01

    Stem cell dynamics define the probability of accumulating mutations within the intestinal epithelium. In this issue of Cell Stem Cell, Nicholson et al. (2018) report that human intestinal stem cell dynamics differ significantly from those of mice and establish that oncogenic mutations are more likely to expand; therefore, "normal" epithelium may carry multiple mutations. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Comparative mutagenesis of human cells in vivo and in vitro

    International Nuclear Information System (INIS)

    Thilly, W.G.

    1992-05-01

    This report discusses measuring methods of point mutations; high density cell cultures for low dose studies; measurement and sequence determination of mutations in DNA; the mutational spectra of styrene oxide and ethlyene oxide in TK-6 cells; mutational spectrum of Cr in human lymphoblast cells; mutational spectra of radon in TK-6 cells; and the mutational spectra of smokeless tobacco

  5. Characterizing the radioresponse of pluripotent and multipotent human stem cells.

    Directory of Open Access Journals (Sweden)

    Mary L Lan

    Full Text Available The potential capability of stem cells to restore functionality to diseased or aged tissues has prompted a surge of research, but much work remains to elucidate the response of these cells to genotoxic agents. To more fully understand the impact of irradiation on different stem cell types, the present study has analyzed the radioresponse of human pluripotent and multipotent stem cells. Human embryonic stem (ES cells, human induced pluripotent (iPS cells, and iPS-derived human neural stem cells (iPS-hNSCs cells were irradiated and analyzed for cell survival parameters, differentiation, DNA damage and repair and oxidative stress at various times after exposure. While irradiation led to dose-dependent reductions in survival, the fraction of surviving cells exhibited dose-dependent increases in metabolic activity. Irradiation did not preclude germ layer commitment of ES cells, but did promote neuronal differentiation. ES cells subjected to irradiation exhibited early apoptosis and inhibition of cell cycle progression, but otherwise showed normal repair of DNA double-strand breaks. Cells surviving irradiation also showed acute and persistent increases in reactive oxygen and nitrogen species that were significant at nearly all post-irradiation times analyzed. We suggest that stem cells alter their redox homeostasis to adapt to adverse conditions and that radiation-induced oxidative stress plays a role in regulating the function and fate of stem cells within tissues compromised by radiation injury.

  6. Sequential cancer mutations in cultured human intestinal stem cells

    NARCIS (Netherlands)

    Drost, Jarno; van Jaarsveld, Richard H.; Ponsioen, Bas; Zimberlin, Cheryl; van Boxtel, Ruben; Buijs, Arjan; Sachs, Norman; Overmeer, René M.; Offerhaus, G. Johan; Begthel, Harry; Korving, Jeroen; van de Wetering, Marc; Schwank, Gerald; Logtenberg, Meike; Cuppen, Edwin; Snippert, Hugo J.; Medema, Jan Paul; Kops, Geert J. P. L.; Clevers, Hans

    2015-01-01

    Crypt stem cells represent the cells of origin for intestinal neoplasia. Both mouse and human intestinal stem cells can be cultured in medium containing the stem-cell-niche factors WNT, R-spondin, epidermal growth factor (EGF) and noggin over long time periods as epithelial organoids that remain

  7. Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics

    Directory of Open Access Journals (Sweden)

    Nigel G. Kooreman

    2017-08-01

    Full Text Available There is growing interest in using embryonic stem cell (ESC and induced pluripotent stem cell (iPSC derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an “allogenized” mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts.

  8. Chondrosarcoma of the hyoid bone - Report of a case and a literature review of the suitable treatment strategy.

    Science.gov (United States)

    Maki, Daisuke; Mori, Taisuke; Teshima, Masanori; Kobayashi, Kenya; Matsumoto, Fumihiko; Sakai, Akihiro; Okami, Kenji; Yoshimoto, Seiichi

    2017-10-01

    Chondrosarcoma is a rare malignant tumor occurring in the trunk and long bones. We present an extremely rare case of chondrosarcoma of the hyoid bone with clinical and pathological correlation and a literature review. We searched all cases of the hyoid chondrosarcoma in PubMed (MEDLINE) between 1990 and 2015. Eighteen cases were analyzed, including the present case. Most of them were low grade type. In 12 cases where intraoperative findings were recorded, no adhesion to the surrounding tissue was observed. Chondrosarcoma of the hyoid bone is usually low grade type, and there may be no invasion to the adjacent structures even if invasion is suspected by imaging findings. In order to preserve swallowing and laryngeal function, total hyoidectomy without laryngectomy should be indicated according to the intraoperative findings. Needle biopsy is an effective diagnostic technique, but open biopsy should be avoided to prevent the dissemination. To the best of our knowledge, this is the first presentation of hyoid bone chondrosarcoma with the investigation of intraoperative findings and pre-operative diagnostic modality. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Clinicopathological significance of p16, cyclin D1, Rb and MIB-1 levels in skull base chordoma and chondrosarcoma

    Directory of Open Access Journals (Sweden)

    Jun-qi Liu

    2015-09-01

    Full Text Available Objective: To investigate the expression of p16, cyclin D1, retinoblastoma tumor suppressor protein (Rb and MIB-1 in skull base chordoma and chondrosarcoma tissues, and to determine the clinicopathological significance of the above indexes in these diseases. Methods: A total of 100 skull base chordoma, 30 chondrosarcoma, and 20 normal cartilage tissue samples were analyzed by immunohistochemistry. The expression levels of p16, cyclinD1, Rb and MIB-1 proteins were assessed for potential correlation with the clinicopathological features. Results: As compared to normal cartilage specimen (control, there was decreased expression of p16, and increased expression of cyclin D1, Rb and MIB-1 proteins, in both skull base chordoma and chondrosarcoma specimens. MIB-1 LI levels were significantly increased in skull base chordoma specimens with negative expression of p16, and positive expression of cyclin D1 and Rb (P  0.05. However, p16 and MIB-1 levels correlated with the intradural invasion, and expression of p16, Rb and MIB-1 correlated with the number of tumor foci (P < 0.05. Further, the expression of p16 and MIB-1 appeared to correlate with the prognosis of patients with skull base chordoma. Conclusions: The abnormal expression of p16, cyclin D1 and Rb proteins might be associated with the tumorigenesis of skull base chordoma and chondrosarcoma. Keywords: p16, Cyclin D1, Rb, MIB-1, Skull base chordoma, Skull base chondrosarcoma

  10. Laryngeal chondrosarcoma of the arytenoid cartilage presenting as bilateral vocal fold immobility: a case report and literature review.

    Science.gov (United States)

    Hu, Rong; Xu, Wen; Liu, Honggang; Chen, Xuejun

    2014-01-01

    To describe an atypical case of laryngeal chondrosarcoma of arytenoid cartilage presenting as bilateral vocal fold immobility and to avoid potential missed diagnosis. Our case study included a detail history, physical and radiological examination, laryngeal electromyography (LEMG), and surgical treatment and pathology analysis. We compared it with the previously discussed cases of chondrosarcoma of arytenoid cartilage in the literature. Chondrosarcomas of the arytenoid cartilage is rare, and to date only approximately 10 cases have been reported. We reported a case of a 51-year-old man with 1 month of persistent dyspnea presenting with bilateral vocal fold immobility without neoplasms in larynx. The LEMG showed no obvious abnormality. The cervical-enhanced computed tomography (CT) found no significant signs of a mass except for localized high-density areas in arytenoid cartilage. Right arytenoidectomy and biopsy were performed under general anesthesia with CO2 laser with the pathological diagnosis of chondroma. A total laryngectomy was performed 2 years later, and low-grade chondrosarcoma was the final diagnosis. Laryngeal chondrosarcomas of the arytenoid cartilage are rare. It is easily neglected, especially in those cases presenting with idiopathic vocal fold immobility without any obvious signs of neoplasms. The LEMG and laryngeal CT are necessary. Sometimes, a biopsy of the arytenoid cartilage is essential. Copyright © 2014 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  11. Nanoscale Mechanical Stimulation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    H Nikukar

    2014-05-01

    We observed significant responses after 1 and 2-week stimulations in cell number, cell shapes and phenotypical markers. Microarray was performed for all groups. Cell count showed normal cell growth with stimulation. However, cell surface area, cell perimeter, and arboration after 1-week stimulation showed significant increases. Immunofluorescent studies have showed significant increase in osteocalcin production after stimulation. Conclusions: Nanoscale mechanical vibration showed significant changes in human mesenchymal stem cell behaviours. Cell morphology changed to become more polygonal and increased expression of the osteoblast markers were noted. These findings with gene regulation changes suggesting nanoscale mechanostimulation has stimulated osteoblastogenesis.  Keywords:  Mesenchymal, Nanoscale, Stem Cells.

  12. Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells.

    Science.gov (United States)

    Vieira Torquato, Heron F; Ribeiro-Filho, Antonio C; Buri, Marcus V; Araújo Júnior, Roberto T; Pimenta, Renata; de Oliveira, José Salvador R; Filho, Valdir C; Macho, Antonio; Paredes-Gamero, Edgar J; de Oliveira Martins, Domingos T

    2017-04-01

    Canthin-6-one is a natural product isolated from various plant genera and from fungi with potential antitumor activity. In the present study, we evaluate the antitumor effects of canthin-6-one in human myeloid leukemia lineages. Kasumi-1 lineage was used as a model for acute myeloid leukemia. Cells were treated with canthin-6-one and cell death, cell cycle and differentiation were evaluated in both total cells (Lin + ) and leukemia stem cell population (CD34 + CD38 - Lin -/low ). Among the human lineages tested, Kasumi-1 was the most sensitive to canthin-6-one. Canthin-6-one induced cell death with apoptotic (caspase activation, decrease of mitochondrial potential) and necrotic (lysosomal permeabilization, double labeling of annexin V/propidium iodide) characteristics. Moreover, canthin-6-one induced cell cycle arrest at G 0 /G 1 (7μM) and G 2 (45μM) evidenced by DNA content, BrdU incorporation and cyclin B1/histone 3 quantification. Canthin-6-one also promoted differentiation of Kasumi-1, evidenced by an increase in the expression of myeloid markers (CD11b and CD15) and the transcription factor PU.1. Furthermore, a reduction of the leukemic stem cell population and clonogenic capability of stem cells were observed. These results show that canthin-6-one can affect Kasumi-1 cells by promoting cell death, cell cycle arrest and cell differentiation depending on concentration used. Canthin-6-one presents an interesting cytotoxic activity against leukemic cells and represents a promising scaffold for the development of molecules for anti-leukemic applications, especially by its anti-leukemic stem cell activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Comparison of the glycosphingolipids of human-induced pluripotent stem cells and human embryonic stem cells.

    Science.gov (United States)

    Säljö, Karin; Barone, Angela; Vizlin-Hodzic, Dzeneta; Johansson, Bengt R; Breimer, Michael E; Funa, Keiko; Teneberg, Susann

    2017-04-01

    High expectations are held for human-induced pluripotent stem cells (hiPSC) since they are established from autologous tissues thus overcoming the risk of allogeneic immune rejection when used in regenerative medicine. However, little is known regarding the cell-surface carbohydrate antigen profile of hiPSC compared with human embryonic stem cells (hESC). Here, glycosphingolipids were isolated from an adipocyte-derived hiPSC line, and hiPSC and hESC glycosphingolipids were compared by concurrent characterization by binding assays with carbohydrate-recognizing ligands and mass spectrometry. A high similarity between the nonacid glycosphingolipids of hiPSC and hESC was found. The nonacid glycosphingolipids P1 pentaosylceramide, x2 pentaosylceramide and H type 1 heptaosylceramide, not previously described in human pluripotent stem cells (hPSC), were characterized in both hiPSC and hESC. The composition of acid glycosphingolipids differed, with increased levels of GM3 ganglioside, and reduced levels of GD1a/GD1b in hiPSC when compared with hESC. In addition, the hESC glycosphingolipids sulf-globopentaosylceramide and sialyl-globotetraosylceramide were lacking in hiPSC. Neural stem cells differentiating from hiPSC had a reduced expression of sialyl-lactotetra, whereas expression of the GD1a ganglioside was significantly increased. Thus, while sialyl-lactotetra is a marker of undifferentiated hPSC, GD1a is a novel marker of neural differentiation. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. A DNA Vaccine Protects Human Immune Cells against Zika Virus Infection in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Guohua Yi

    2017-11-01

    Full Text Available A DNA vaccine encoding prM and E protein has been shown to induce protection against Zika virus (ZIKV infection in mice and monkeys. However, its effectiveness in humans remains undefined. Moreover, identification of which immune cell types are specifically infected in humans is unclear. We show that human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We also show that a DNA vaccine encoding full length prM and E protein protects humanized mice from ZIKV infection. Following administration of the DNA vaccine, humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and neutralization assays. Moreover, following ZIKV challenge, vaccinated animals presented virtually no detectable virus in human cells and in serum, whereas unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our results utilizing humanized mice show potential efficacy for a targeted DNA vaccine against ZIKV in humans.

  15. Molecular aging and rejuvenation of human muscle stem cells

    DEFF Research Database (Denmark)

    Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J

    2009-01-01

    . Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth...... factor beta (TGF-beta)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular......Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans...

  16. Generation of Corneal Keratocytes from Human Embryonic Stem Cells.

    Science.gov (United States)

    Hertsenberg, Andrew J; Funderburgh, James L

    2016-01-01

    Human Embryonic Stem Cells (hESC) offer an important resource as a limitless supply of any differentiated cell type of the human body. Keratocytes, cells from the corneal stroma, may have the potential for restoration of vision in cell therapy and biomedical engineering applications, but these specialized cells are not readily expanded in vitro. Here we describe a two-part method to produce keratocytes from the H1 hESC cell line. The hESC cells, maintained and expanded in feeder-free culture medium are first differentiated to neural crest cells using the stromal-derived inducing activity (SDIA) of the PA6 mouse embryonic fibroblast cell line. The resulting neural crest cells are selected by their expression of cell-surface CD271 and subsequently cultured as 3D pellets in a defined differentiation medium to induce a keratocyte phenotype.

  17. In vitro proliferation of adult human beta-cells.

    Directory of Open Access Journals (Sweden)

    Sabine Rutti

    Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

  18. Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

    Science.gov (United States)

    Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

    2017-08-02

    The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS

  19. Identification of molecules derived from human fibroblast feeder cells that support the proliferation of human embryonic stem cells

    DEFF Research Database (Denmark)

    Anisimov, Sergey V.; Christophersen, Nicolaj S.; Correia, Ana S.

    2011-01-01

    The majority of human embryonic stem cell lines depend on a feeder cell layer for continuous growth in vitro, so that they can remain in an undifferentiated state. Limited knowledge is available concerning the molecular mechanisms that underlie the capacity of feeder cells to support both...... the proliferation and pluripotency of these cells. Importantly, feeder cells generally lose their capacity to support human embryonic stem cell proliferation in vitro following long-term culture. In this study, we performed large-scale gene expression profiles of human foreskin fibroblasts during early...... foreskin fibroblasts to serve as feeder cells for human embryonic stem cell cultures. Among these, the C-KIT, leptin and pigment epithelium-derived factor (PEDF) genes were the most interesting candidates....

  20. Nucleosome Organization in Human Embryonic Stem Cells.

    Directory of Open Access Journals (Sweden)

    Puya G Yazdi

    Full Text Available The fundamental repeating unit of eukaryotic chromatin is the nucleosome. Besides being involved in packaging DNA, nucleosome organization plays an important role in transcriptional regulation and cellular identity. Currently, there is much debate about the major determinants of the nucleosome architecture of a genome and its significance with little being known about its role in stem cells. To address these questions, we performed ultra-deep sequencing of nucleosomal DNA in two human embryonic stem cell lines and integrated our data with numerous epigenomic maps. Our analyses have revealed that the genome is a determinant of nucleosome organization with transcriptionally inactive regions characterized by a "ground state" of nucleosome profiles driven by underlying DNA sequences. DNA sequence preferences are associated with heterogeneous chromatin organization around transcription start sites. Transcription, histone modifications, and DNA methylation alter this "ground state" by having distinct effects on both nucleosome positioning and occupancy. As the transcriptional rate increases, nucleosomes become better positioned. Exons transcribed and included in the final spliced mRNA have distinct nucleosome profiles in comparison to exons not included at exon-exon junctions. Genes marked by the active modification H3K4m3 are characterized by lower nucleosome occupancy before the transcription start site compared to genes marked by the inactive modification H3K27m3, while bivalent domains, genes associated with both marks, lie exactly in the middle. Combinatorial patterns of epigenetic marks (chromatin states are associated with unique nucleosome profiles. Nucleosome organization varies around transcription factor binding in enhancers versus promoters. DNA methylation is associated with increasing nucleosome occupancy and different types of methylations have distinct location preferences within the nucleosome core particle. Finally, computational

  1. Human interleukin for DA cells or leukemia inhibitory factor is released by Vero cells in human embryo coculture.

    Science.gov (United States)

    Papaxanthos-Roche, A; Taupin, J L; Mayer, G; Daniel, J Y; Moreau, J F

    1994-09-01

    In the light of the newly discovered implications of human interleukin for DA cells and leukemia inhibitory factor in embryology, we searched for the presence of this soluble cytokine in the supernatant of Vero cell coculture systems. Using a bioassay as well as a specific ELISA, we demonstrated that Vero cells are able to release large quantities of human interleukin for DA cells and leukemia inhibitory factor in the embryo-growing medium of such cocultures.

  2. Current applications of human pluripotent stem cells: possibilities and challenges.

    Science.gov (United States)

    Ho, Pai-Jiun; Yen, Men-Luh; Yet, Shaw-Fang; Yen, B Linju

    2012-01-01

    Stem cells are self-renewable cells with the differentiation capacity to develop into somatic cells with biological functions. This ability to sustain a renewable source of multi- and/or pluripotential differentiation has brought new hope to the field of regenerative medicine in terms of cell therapy and tissue engineering. Moreover, stem cells are invaluable tools as in vitro models for studying diverse fields, from basic scientific questions such as developmental processes and lineage commitment, to practical application including drug screening and testing. The stem cells with widest differentiation potential are pluripotent stem cells (PSCs), which are rare cells with the ability to generate somatic cells from all three germ layers. PSCs are considered the most optimal choice for therapeutic potential of stem cells, bringing new impetus to the field of regenerative medicine. In this article, we discuss the therapeutic potential of human PSCs (hPSCs) including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), reviewing the current preclinical and clinical data using these stem cells. We describe the classification of different sources of hPSCs, ongoing research, and currently encountered clinical obstacles of these novel and versatile human stem cells.

  3. Sphere-forming cell subpopulations with cancer stem cell properties in human hepatoma cell lines

    Directory of Open Access Journals (Sweden)

    Chen Lei

    2011-06-01

    Full Text Available Abstract Background Cancer stem cells (CSCs are regarded as the cause of tumor formation and recurrence. The isolation and identification of CSCs could help to develop novel therapeutic strategies specifically targeting CSCs. Methods Human hepatoma cell lines were plated in stem cell conditioned culture system allowed for sphere forming. To evaluate the stemness characteristics of spheres, the self-renewal, proliferation, chemoresistance, tumorigenicity of the PLC/PRF/5 sphere-forming cells, and the expression levels of stem cell related proteins in the PLC/PRF/5 sphere-forming cells were assessed, comparing with the parental cells. The stem cell RT-PCR array was performed to further explore the biological properties of liver CSCs. Results The PLC/PRF/5, MHCC97H and HepG2 cells could form clonal nonadherent 3-D spheres and be serially passaged. The PLC/PRF/5 sphere-forming cells possessed a key criteria that define CSCs: persistent self-renewal, extensive proliferation, drug resistance, overexpression of liver CSCs related proteins (Oct3/4, OV6, EpCAM, CD133 and CD44. Even 500 sphere-forming cells were able to form tumors in NOD/SCID mice, and the tumor initiating capability was not decreased when spheres were passaged. Besides, downstream proteins DTX1 and Ep300 of the CSL (CBF1 in humans, Suppressor of hairless in Drosophila and LAG1 in C. elegans -independent Notch signaling pathway were highly expressed in the spheres, and a gamma-secretase inhibitor MRK003 could significantly inhibit the sphere formation ability. Conclusions Nonadherent tumor spheres from hepatoma cell lines cultured in stem cell conditioned medium possess liver CSC properties, and the CSL-independent Notch signaling pathway may play a role in liver CSCs.

  4. Human dental pulp stem cells: Applications in future regenerative medicine

    Science.gov (United States)

    Potdar, Pravin D; Jethmalani, Yogita D

    2015-01-01

    Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells (MSCs) from various human tissues, peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells (DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and β cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine. PMID:26131314

  5. Comprehensive evaluation of leukocyte lineage derived from human hematopoietic cells in humanized mice.

    Science.gov (United States)

    Takahashi, Masayuki; Tsujimura, Noriyuki; Otsuka, Kensuke; Yoshino, Tomoko; Mori, Tetsushi; Matsunaga, Tadashi; Nakasono, Satoshi

    2012-04-01

    Recently, humanized animals whereby a part of the animal is biologically engineered using human genes or cells have been utilized to overcome interspecific differences. Herein, we analyzed the detail of the differentiation states of various human leukocyte subpopulations in humanized mouse and evaluated comprehensively the similarity of the leukocyte lineage between humanized mice and humans. Humanized mice were established by transplanting human CD34(+) cord blood cells into irradiated severely immunodeficient NOD/Shi-scid/IL2Rγ(null) (NOG) mice, and the phenotypes of human cells contained in bone marrow, thymus, spleen and peripheral blood from the mice were analyzed at monthly intervals until 4 months after cell transplantation. The analysis revealed that transplanted human hematopoietic stem cells via the caudal vein homed and engrafted themselves successfully at the mouse bone marrow. Subsequently, the differentiated leukocytes migrated to the various tissues. Almost all of the leukocytes within the thymus were human cells. Furthermore, analysis of the differentiation states of human leukocytes in various tissues and organs indicated that it is highly likely that the human-like leukocyte lineage can be developed in mice. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  6. Wharton's Jelly Derived Mesenchymal Stem Cells: Comparing Human and Horse.

    Science.gov (United States)

    Merlo, Barbara; Teti, Gabriella; Mazzotti, Eleonora; Ingrà, Laura; Salvatore, Viviana; Buzzi, Marina; Cerqueni, Giorgia; Dicarlo, Manuela; Lanci, Aliai; Castagnetti, Carolina; Iacono, Eleonora

    2018-08-01

    Wharton's jelly (WJ) is an important source of mesenchymal stem cells (MSCs) both in human and other animals. The aim of this study was to compare human and equine WJMSCs. Human and equine WJMSCs were isolated and cultured using the same protocols and culture media. Cells were characterized by analysing morphology, growth rate, migration and adhesion capability, immunophenotype, differentiation potential and ultrastructure. Results showed that human and equine WJMSCs have similar ultrastructural details connected with intense synthetic and metabolic activity, but differ in growth, migration, adhesion capability and differentiation potential. In fact, at the scratch assay and transwell migration assay, the migration ability of human WJMSCs was higher (P cells, while the volume of spheroids obtained after 48 h of culture in hanging drop was larger than the volume of equine ones (P cell adhesion ability. This can also revealed in the lower doubling time of equine cells (3.5 ± 2.4 days) as compared to human (6.5 ± 4.3 days) (P cell doubling after 44 days of culture observed for the equine (20.3 ± 1.7) as compared to human cells (8.7 ± 2.4) (P cells showed an higher chondrogenic and osteogenic differentiation ability (P staminal phenotype in human and equine WJMSCs, they showed different properties reflecting the different sources of MSCs.

  7. induced acute cytotoxicity in human cervical epithelial carcinoma cells

    African Journals Online (AJOL)

    Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

  8. Novel human multiple myeloma cell line UHKT-893

    Czech Academy of Sciences Publication Activity Database

    Uherková, L.; Vančurová, I.; Vyhlídalová, I.; Pleschnerová, M.; Špička, I.; Mihalová, R.; Březinová, J.; Hodný, Zdeněk; Čermáková, K.; Polanská, V.; Marinov, I.; Jedelský, P.L.; Kuželová, K.; Stöckbauer, P.

    2013-01-01

    Roč. 37, č. 3 (2013), s. 320-326 ISSN 0145-2126 Institutional support: RVO:68378050 Keywords : human myeloma cell line * human multiple myeloma * plasma cell * IL-6 dependence * immunoglobulin * free light chain Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.692, year: 2013

  9. Secondary Chondrosarcoma of the Upper Thoracic Costovertebral Junction with Neural Foraminal Extension and Compressing the Spinal Cord.

    Science.gov (United States)

    Bouali, Sofiene; Bouhoula, Asma; Maatar, Nidhal; Abderrahmen, Khansa; Boubaker, Adnen; Kallel, Jalel; Jemel, Hafedh

    2016-08-01

    Chondrosarcoma is a rare malignant tumor of bone. This family of tumors can be primary malignant tumors or a secondary malignant transformation of an underlying benign cartilage tumor. Secondary chondrosarcoma arising from a benign solitary costal osteochondroma is extremely rare. Data show that the reported incidence of costal osteochondroma is very low and they are usually found in the anterior region at the costochondral junction. To our knowledge, however, there have been no previous reports, in English literature, describing osteochondroma malignant transformation located in the thoracic costovertebral junction. We report the case of a man with chondrosarcoma arising from the malignant degeneration of an osteochondroma at the right first thoracic costovertebral junction with neural foraminal extension and compressing the spinal cord. Although it is rare in solitary osteochondromas of rib, malignant transformation must always be considered. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Subglottic Chondrosarcoma Presenting Only Mild Acute-Onset Dyspnea: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Su-wei Tsai

    2014-01-01

    Full Text Available Chondrosarcoma is categorized as a malignant cartilaginous tumor, which occurs rarely in the craniofacial region. We report the case of a 68-year-old man with chondrosarcoma in the subglottic area. His chief symptoms were hoarseness and mild dysphagia. A computed tomography scan revealed a lesion with expansion of the cricoid cartilage and marked reduction of the airway. After biopsy, histological inspection showed that chondrocytes are multi-nucleus, their size does not differ much and mitosis is not obvious. These are all characteristics of a low-grade chondrosarcoma. We performed an organ-preserving operation by debulking the low-grade malignant tumor in order to keep a patent airway. No further metastasis or airway compromise was evident during the 1-year follow-up visit.

  11. Human induced pluripotent stem cells on autologous feeders.

    Directory of Open Access Journals (Sweden)

    Kazutoshi Takahashi

    Full Text Available BACKGROUND: For therapeutic usage of induced Pluripotent Stem (iPS cells, to accomplish xeno-free culture is critical. Previous reports have shown that human embryonic stem (ES cells can be maintained in feeder-free condition. However, absence of feeder cells can be a hostile environment for pluripotent cells and often results in karyotype abnormalities. Instead of animal feeders, human fibroblasts can be used as feeder cells of human ES cells. However, one still has to be concerned about the existence of unidentified pathogens, such as viruses and prions in these non-autologous feeders. METHODOLOGY/PRINCIPAL FINDINGS: This report demonstrates that human induced Pluripotent Stem (iPS cells can be established and maintained on isogenic parental feeder cells. We tested four independent human skin fibroblasts for the potential to maintain self-renewal of iPS cells. All the fibroblasts tested, as well as their conditioned medium, were capable of maintaining the undifferentiated state and normal karyotypes of iPS cells. Furthermore, human iPS cells can be generated on isogenic parental fibroblasts as feeders. These iPS cells carried on proliferation over 19 passages with undifferentiated morphologies. They expressed undifferentiated pluripotent cell markers, and could differentiate into all three germ layers via embryoid body and teratoma formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that autologous fibroblasts can be not only a source for iPS cells but also be feeder layers. Our results provide a possibility to solve the dilemma by using isogenic fibroblasts as feeder layers of iPS cells. This is an important step toward the establishment of clinical grade iPS cells.

  12. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe

    2016-01-01

    carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils...... incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack...... of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident....

  13. Freeze-Dried Human Red Blood Cells

    Science.gov (United States)

    1992-04-15

    period in the liquid state. 2. The levels of glycolytic intermediates (ATP, adenosine 5’triphosphate; 2,3-DPG 2, 3- diphosphoglycerate ) in rehydrated...8217 diphosphate, ADP; adenosine 5 monophosphate, AMP; 2,3- diphosphoglycerate . 2.3-DPG and lactate: (2) measurement of cell indices (mean cell volume (MCV), mean...monophosphate: 2,3-DPG. 2.3- diphosphoglycerate : MCV. Mean Cell Volume: MCH, Mean Cell Hemoglobin: MCHC, Mean Cell Hemoglobin Concentrations. ** Lactate levels

  14. CD1 and mycobacterial lipids activate human T cells.

    Science.gov (United States)

    Van Rhijn, Ildiko; Moody, D Branch

    2015-03-01

    For decades, proteins were thought to be the sole or at least the dominant source of antigens for T cells. Studies in the 1990s demonstrated that CD1 proteins and mycobacterial lipids form specific targets of human αβ T cells. The molecular basis by which T-cell receptors (TCRs) recognize CD1-lipid complexes is now well understood. Many types of mycobacterial lipids function as antigens in the CD1 system, and new studies done with CD1 tetramers identify T-cell populations in the blood of tuberculosis patients. In human populations, a fundamental difference between the CD1 and major histocompatibility complex systems is that all humans express nearly identical CD1 proteins. Correspondingly, human CD1 responsive T cells show evidence of conserved TCRs. In addition to natural killer T cells and mucosal-associated invariant T (MAIT cells), conserved TCRs define other subsets of human T cells, including germline-encoded mycolyl-reactive (GEM) T cells. The simple immunogenetics of the CD1 system and new investigative tools to measure T-cell responses in humans now creates a situation in which known lipid antigens can be developed as immunodiagnostic and immunotherapeutic reagents for tuberculosis disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. On the development of extragonadal and gonadal human germ cells

    Directory of Open Access Journals (Sweden)

    A. Marijne Heeren

    2016-02-01

    Full Text Available Human germ cells originate in an extragonadal location and have to migrate to colonize the gonadal primordia at around seven weeks of gestation (W7, or five weeks post conception. Many germ cells are lost along the way and should enter apoptosis, but some escape and can give rise to extragonadal germ cell tumors. Due to the common somatic origin of gonads and adrenal cortex, we investigated whether ectopic germ cells were present in the human adrenals. Germ cells expressing DDX4 and/or POU5F1 were present in male and female human adrenals in the first and second trimester. However, in contrast to what has been described in mice, where ‘adrenal’ and ‘ovarian’ germ cells seem to enter meiosis in synchrony, we were unable to observe meiotic entry in human ‘adrenal’ germ cells until W22. By contrast, ‘ovarian’ germ cells at W22 showed a pronounced asynchronous meiotic entry. Interestingly, we observed that immature POU5F1+ germ cells in both first and second trimester ovaries still expressed the neural crest marker TUBB3, reminiscent of their migratory phase. Our findings highlight species-specific differences in early gametogenesis between mice and humans. We report the presence of a population of ectopic germ cells in the human adrenals during development.

  16. Defective repair of UV-damaged DNA in human tumor and SV40-transformed human cells but not in adenovirus-transformed human cells

    International Nuclear Information System (INIS)

    Rainbow, A.J.

    1989-01-01

    The DNA repair capacities of five human tumor cell lines, one SV40-transformed human cell line and one adenovirus-transformed human cell line were compared with that of normal human fibroblasts using a sensitive host cell reactivation (HCR) technique. Unirradiated and UV-irradiated suspensions of adenovirus type 2 (Ad 2) were assayed for their ability to form viral structural antigens (Vag) in the various cell types using immunofluorescent staining. The survival of Vag formation for UV-irradiated Ad 2 was significantly reduced in all the human tumor cell lines and the SV40-transformed human line compared to the normal human fibroblasts, but was apparently normal in the adenovirus-transformed human cells. D 0 values for the UV survival of Ad 2 Vag synthesis in the tumor and virally transformed lines expressed as a percentage of that obtained on normal fibroblast strains were used as a measure of DNA repair capacity. Percent HCR values ranged from 26 to 53% in the tumor cells. These results indicate a deficiency in the repair of UV-induced DNA damage associated with human tumorigenesis and the transformation of human cells by SV40 but not the transformation of human cells by adenovirus. (author)

  17. Generation of hepatocyte- and endocrine pancreatic-like cells from human induced endodermal progenitor cells

    NARCIS (Netherlands)

    Sambathkumar, Rangarajan; Akkerman, Renate; Dastidar, Sumitava; Roelandt, Philip; Kumar, Manoj; Bajaj, Manmohan; Mestre Rosa, Ana Rita; Helsen, Nicky; Vanslembrouck, Veerle; Kalo, Eric; Khurana, Satish; Laureys, Jos; Gysemans, Conny; Faas, Marijke M; de Vos, Paul; Verfaillie, Catherine M

    2018-01-01

    Multipotent Adult Progenitor Cells (MAPCs) are one potential stem cell source to generate functional hepatocytes or β-cells. However, human MAPCs have less plasticity than pluripotent stem cells (PSCs), as their ability to generate endodermal cells is not robust. Here we studied the role of 14

  18. Proteomic analysis of human blastocoel fluid and blastocyst cells

    DEFF Research Database (Denmark)

    Jensen, Pernille; Beck, Hans Christian; Petersen, Jørgen

    2013-01-01

    Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of the blastocyst and can differentiate into any cell type in the human body. These cells hold a great potential for regenerative medicine, but to obtain enough cells needed for medical treatment, culture is required......, the blastocoel fluid, which is in contact with all the cells in the blastocyst, including hESCs. Fifty-three surplus human blastocysts were donated after informed consent, and blastocoel fluid was isolated by micromanipulation. Using highly sensitive nano-high-pressure liquid chromatography-tandem mass...... from the ICM of the human blastocyst are exposed to via the blastocoel fluid. These results can be an inspiration for the development of improved culture conditions for hESCs....

  19. Abnormal number cell division of human thyroid anaplastic carcinoma cell line, SW 1736

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2015-12-01

    Full Text Available Cell division, during which a mother cell usually divides into two daughter cells during one cell cycle, is the most important physiological event of cell biology. We observed one-to-four cell division during imaging of live SW1736 human thyroid anaplastic carcinoma cells transfected with a plasmid expressing the hybrid protein of green fluorescent protein and histone 2B (plasmid eGFP-H2B. Analysis of the images revealed a mother cell divided into four daughter cells. And one of the abnormally divided daughter cells subsequently formed a dinucleate cell.

  20. The use of human cells in biomedical research and testing.

    Science.gov (United States)

    Combes, Robert D

    2004-06-01

    The ability to use human cells in biomedical research and testing has the obvious advantage over the use of laboratory animals that the need for species extrapolation is obviated, due to the presence of more-relevant morphological, physiological and biochemical properties, including receptors. Moreover, human cells exhibit the same advantages as animal cells in culture in that different cell types can be used, from different tissues, with a wide range of techniques, to investigate a wide variety of biological phenomena in tissue culture. Human cells can also be grown as organotypic cultures to facilitate the extrapolation from cells to whole organisms. Human cell lines have been available for many years on an ad hoc basis from individual researchers, and also from recognised sources, such as the European Collection of Animal Cell Cultures (ECACC) and, in the USA, the Human Cell Culture Centre (HCCC). Such cells have usually been derived from tumours and this has restricted the variety of types of cells available. This problem has been addressed by using primary human cells that can be obtained from a variety of sources, such as cadavers, diseased tissue, skin strips, peripheral blood, buccal cavity smears, hair follicles and surgical waste from biopsy material that is unsuitable for transplantation purposes. However, primary human cells need to be obtained, processed, distributed and handled in a safe and ethical manner. They also have to be made available at the correct time to researchers very shortly after they become available. It is only comparatively recently that the safe and controlled acquisition of surgical waste and non-transplantable human tissues has become feasible with the establishment of several human tissue banks. Recently, the formation of a UK and European centralised network for human tissue supply has been initiated. The problems of short longevity and loss of specialisation in culture are being approached by: a) cell immortalisation to