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GSE72780
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Inflammatory Bowel Diseases are associated with marked alterations of IECs with a subsequent loss of barrier function.
Publication Title
Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Prenylation is a post-translational modification of proteins consisting on the attachment of a lipid residue (isoprenoid). GGTase-I is one of the prenyltransferases catalyzing prenylation.
Publication Title
Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
To uncover molecular mechanisms specifically involved in the pathogenesis of colitis-associated colon cancer (CAC), we studied tumorigenesis in experimental models of CAC and sporadic CRC that mimic characteristics of human CRC. Using comparative whole genome expression profiling, we observed differential expression of epiregulin (Ereg) in mouse models of colitis-associated, but not sporadic colorectal cancer. Similarly, highly significant upregulation of Ereg expression was found in cohorts of patients with colitis-associated cancer in inflammatory bowel disease but not in sporadic colorectal cancer. Furthermore, tumor-associated fibroblasts were identified as major source of Ereg in colitis-associated neoplasias. Functional studies showed that Ereg-deficient mice, although more prone to colitis, are strongly protected from colitis-associated tumors, and data from serial endoscopic studies revealed that Ereg promotes growth rather than initiation of tumors.
Publication Title
Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaHiSeq2000
Description
Anti-angiogenic therapy is commonly used for the treatment of CRC. Although patients derive some clinical benefit, treatment resistance inevitably occurs. The MET signaling pathway has been proposed to be a major contributor of resistance to anti-angiogenic therapy. MET is upregulated in response to VEGF pathway inhibition and plays an essential role in tumorigenesis and progression of tumors. In this study we set out to determine the efficacy of cabozantinib in a preclinical CRC PDTX model. We demonstrate potent inhibitory effects on tumor growth in 80% of tumors treated. The greatest antitumor effects were observed in tumors that possess a mutation in the PIK3CA gene. The underlying antitumor mechanisms of cabozantinib consisted of inhibition of angiogenesis and Akt activation and significantly decreased expression of genes involved in the PI3K pathway. These findings support further evaluation of cabozantinib in patients with CRC. PIK3CA mutation as a predictive biomarker of sensitivity is intriguing and warrants further elucidation. A clinical trial of cabozantinib in refractory metastatic CRC is being activated. Overall design: CRC PDTX Model treated with cabozantinib
Publication Title
Potent antitumor activity of cabozantinib, a c-MET and VEGFR2 inhibitor, in a colorectal cancer patient-derived tumor explant model.
Sample Metadata Fields
No sample metadata fields
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