Abstract:
Background:Colorectal cancer (CRC) is a major cause of cancer-related deaths, and tumor-related comorbidities additionally lower life quality and survival. Mutations in the tumor suppressor adenomatous polyposis coli (APC) are associated with sporadic CRC and familial adenomatous polyposis (FAP), which results in the growth of multiple intestinal cancer lesions. In some cases, inflammatory bowel diseases (IBDs) are additionally observed in CRC patients. Although APC mutations have been shown to increase bone mineral density (BMD), inflammation is associated with reduced BMD and an elevated fracture risk in IBD patients. Methods:To determine the consequences of APC-driven intestinal tumorigenesis and additional inflammation on bone parameters, we utilized an APC1638N/+ mouse model. We treated 1 cohort of APC wild-type and mutant animals with dextran sodium sulfate (DSS) to induce colorectal inflammation. All mice were killed at the same age and stratified according to their tumor burden. Results:As expected, a heterozygous APC mutation increased intestinal tumor numbers and the cortical BMD. This effect on bone was abrogated in mice with high intestinal tumor numbers. Moreover, we found that high tumor burden elevated bone fragility in APC-mutated mice. After DSS treatment, there were no significant changes in bone parameters of control mice. In contrast, in combination with inflammation, bone biomechanical properties severely deteriorated at high tumor burdens in APC1638N/+ animals. Conclusions:Together, not only were bone parameters affected by APC status and inflammation, but also high intestinal tumor numbers, especially when combined with inflammation, were associated with an osteoporotic phenotype.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Saul D,Schilling AF,Kosinsky RLdoi
10.1093/ibd/izy234subject
Has Abstractpub_date
2018-10-12 00:00:00pages
2386-2393issue
11eissn
1078-0998issn
1536-4844pii
5048409journal_volume
24pub_type
杂志文章abstract::After 20 years of successful targeting of pro-inflammatory cytokines for the treatment of IBD, an alternative therapeutic strategy has emerged, based on several decades of advances in understanding the pathogenesis of IBD. The targeting of molecules involved in leukocyte traffic has recently become a safe and effectiv...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
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更新日期:2019-01-10 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
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更新日期:2020-04-11 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,随机对照试验
doi:10.1002/ibd.20505
更新日期:2008-10-01 00:00:00
abstract:BACKGROUND:Ulcerative colitis is associated with increased colon permeability resulting in bacterial translocation into the lamina propria. We investigate the importance of the Toll-like receptor (TLR) regulating protein IL-1 receptor-associated kinase M (IRAK-M) using the erosive dextran sulfate sodium (DSS)-induced m...
journal_title:Inflammatory bowel diseases
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21196
更新日期:2010-08-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200407000-00013
更新日期:2004-07-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
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更新日期:2020-01-06 00:00:00
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pub_type: 杂志文章
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更新日期:2014-03-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
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更新日期:2017-08-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
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更新日期:2012-06-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200403000-00008
更新日期:2004-03-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21308
更新日期:2011-01-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-199911000-00005
更新日期:1999-11-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21023
更新日期:2009-12-01 00:00:00
abstract::: Patients with ulcerative colitis are at increased risk for colorectal adenocarcinoma compared with the general population. Although surveillance for colorectal malignancy and dysplasia (a premalignant lesion) has been recommended, a benefit in reducing mortality from colorectal cancer via surveillance or prophylacti...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
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更新日期:2017-10-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
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更新日期:2012-09-01 00:00:00
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更新日期:2020-01-06 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20890
更新日期:2009-08-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2021-01-02 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,随机对照试验
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更新日期:2012-02-01 00:00:00
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pub_type: 杂志文章,meta分析
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更新日期:2018-11-29 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20265
更新日期:2007-12-01 00:00:00