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• W2810588153 abstract "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. 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. 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. 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." @default.
• W2810588153 created "2018-07-10" @default.
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• W2810588153 date "2018-07-03" @default.
• W2810588153 modified "2023-09-26" @default.
• W2810588153 title "Intestinal Inflammation and Tumor Burden as Determinants for Bone Fragility in APC-Driven Tumorigenesis" @default.
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• W2810588153 doi "https://doi.org/10.1093/ibd/izy234" @default.
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