Abstract:
:Cellular mechanisms that account for tumour osteolysis associated with Ewing's sarcoma are uncertain. Osteoclasts are marrow-derived multinucleated cells (MNCs) that effect tumour osteolysis. Osteoclasts are known to form from macrophages by both receptor activator for nuclear factor-kappaB (RANK) ligand (RANKL)-dependent and -independent mechanisms. In this study, our aim has been to determine whether tumour-associated macrophages (TAMs) isolated from Ewing's sarcoma are capable of differentiating into osteoclasts and to characterise the cellular and humoral mechanisms whereby this occurs. Tumour-associated macrophages were isolated from two Ewing's sarcomas and cultured on both coverslips and dentine slices for up to 21 days with soluble RANKL and macrophage colony stimulating factor (M-CSF). Osteoclast formation from TAMs (CD14+) was evidenced by the formation of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR)-positive MNCs, which were capable of carrying out lacunar resorption. This osteoclast formation was inhibited by the addition of bisphosphonates. Both Ewing's sarcoma-derived fibroblasts and some bone stromal cells expressed RANKL and supported osteoclast formation by a contact-dependent mechanism. We also found that osteoclast differentiation occurred when Ewing's TAMs were cultured with tumour necrosis factor (TNF)-alpha in the presence of M-CSF and that TC71 Ewing's sarcoma cells stimulated osteoclast formation through the release of a soluble factor, the action of which was abolished by an antibody to TNF-alpha. These results indicate that TAMs in Ewing's sarcoma are capable of osteoclast differentiation by both RANKL-dependent and TNF-alpha-dependent mechanisms and that Ewing's sarcoma cells produce osteoclastogenic factor(s). Our findings suggest that anti-resorptive and anti-osteoclastogenic therapies may be useful in inhibiting the osteolysis of Ewing's sarcoma.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Lau YS,Adamopoulos IE,Sabokbar A,Giele H,Gibbons CL,Athanasou NAdoi
10.1038/sj.bjc.6603774subject
Has Abstractpub_date
2007-06-04 00:00:00pages
1716-22issue
11eissn
0007-0920issn
1532-1827pii
6603774journal_volume
96pub_type
杂志文章abstract::The binding of ring-labelled and side-chain labelled misonidazole to hypoxic cells in monolayer and spheroid cultures of mammalian cells has been compared. The kinetics and patterns of binding for the two labelled compounds are indistinguishable. This finding has implications for the mechanism of binding and for the d...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1985.33
更新日期:1985-02-01 00:00:00
abstract::Forty-three children with malignant soft tissue sarcomas (IRS Groups II-IV) were treated with rapid dose delivery chemotherapy protocol comprising six courses of vincristine, adriamycin and cyclophosphamide, given in most cases within 8 weeks (Rapid VAC). This was followed in 36 patients by high dose melphalan with au...
journal_title:British journal of cancer
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.375
更新日期:2015-12-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.127
更新日期:1989-04-01 00:00:00
abstract:BACKGROUND:Anti-EGFR antibody, cetuximab, improves overall survival (OS) in K-ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor receptor ligand epiregulin (EREG) gene expression may further predict cetuximab benefit. METHODS:Tumour samples from a phase III clinical trial of cetuximab plu...
journal_title:British journal of cancer
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doi:10.1038/bjc.2013.753
更新日期:2014-02-04 00:00:00
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journal_title:British journal of cancer
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doi:10.1038/bjc.1992.389
更新日期:1992-11-01 00:00:00
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journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1994.372
更新日期:1994-10-01 00:00:00
abstract::We screened 50 glioblastomas for P53 mutations. Five glioblastomas showed heterozygous mutations, while three were putatively heterozygous. Six of these eight glioblastomas showed elimination of wild-type P53 mRNA. These results strongly suggest that some sort of mechanism(s) favouring mutated over wild-type P53 mRNA ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604258
更新日期:2008-04-22 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.459
更新日期:1995-10-01 00:00:00
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journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,评审
doi:10.1038/sj.bjc.6690715
更新日期:1999-10-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.366
更新日期:2014-08-26 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.363
更新日期:1995-08-01 00:00:00
abstract::This study was undertaken to investigate the intracellular induction of reactive oxygen species (ROS) by cis-dichlorodiammineplatinum (CDDP) and the augmentation of their cytotoxicity in bladder cancer cells (KU7) by enhancement of ROS generation by the glutathione (GSH) depletors buthionine sulphoximine (BSO) and die...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.363
更新日期:1997-01-01 00:00:00
abstract::Detailed data were provided by the Oxford Survey of Childhood Cancer OSCC on deaths from childhood cancer in Britain after irradiation of the fetus during diagnostic radiology of the mother. In each age group at death, 0-5, 6-9 and 10-15 years, excess cancer deaths decreased suddenly for births in and after 1958. A ma...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/bjc.1990.249
更新日期:1990-07-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.528
更新日期:1998-08-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.198
更新日期:1989-06-01 00:00:00
abstract:BACKGROUND:For patients with locally advanced rectal cancer (LARC), it is unclear whether neoadjuvant chemoradiotherapy-induced pathologic complete response (pCR) individuals would further benefit from adjuvant chemotherapy (ACT). METHODS:The pCR individuals who received different ACT cycles were paired by propensity ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0989-1
更新日期:2020-10-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.bjc.6602220
更新日期:2004-11-29 00:00:00
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pub_type: 杂志文章
doi:10.1038/bjc.1971.53
更新日期:1971-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2013-05-28 00:00:00
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pub_type: 杂志文章
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更新日期:1989-12-01 00:00:00
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doi:10.1038/sj.bjc.6605236
更新日期:2009-09-15 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1995-10-01 00:00:00
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journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,多中心研究
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pub_type: 临床试验,杂志文章
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更新日期:2004-11-15 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.275
更新日期:2016-10-11 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.389
更新日期:2017-01-03 00:00:00