Publications by authors named "Christina E Destefano Shields"
Colorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced by inflammation, mutagens, and/or microbiota. Colorectal cancers with activating mutations in are associated with distinct clinical characteristics, although the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (Min) enterotoxigenic (ETBF) murine model is characterized by IL17-dependent, distal colon adenomas.
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- Polyamines like putrescine, spermidine, and spermine play key roles in biological processes such as inflammation and cancer development, with spermine oxidase (SMOX) helping to regulate their levels.
- Research using SMOX-deficient mice revealed its involvement in both gastric inflammation and colitis models, showing that SMOX deficiency reduces histological damage and inflammation in infected mice but worsens outcomes in DSS-induced colitis.
- In summary, SMOX exhibits complex effects on immune responses depending on the type of colitis, highlighting its role in both promoting and protecting against inflammation linked to polyamine metabolism.
Individuals with sporadic colorectal cancer (CRC) frequently harbor abnormalities in the composition of the gut microbiome; however, the microbiota associated with precancerous lesions in hereditary CRC remains largely unknown. We studied colonic mucosa of patients with familial adenomatous polyposis (FAP), who develop benign precursor lesions (polyps) early in life. We identified patchy bacterial biofilms composed predominately of and Genes for colibactin () and toxin (), encoding secreted oncotoxins, were highly enriched in FAP patients' colonic mucosa compared to healthy individuals.
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- Pro-carcinogenic bacteria, specifically enterotoxigenic Bacteroides fragilis (ETBF), are linked to the onset and promotion of colon cancer through complex immune responses.
- The Bacteroides fragilis toxin (BFT) initiates an inflammatory response in colonic epithelial cells (CECs) involving signaling pathways like IL-17R, NF-κB, and Stat3.
- IL-17-driven NF-κB activation creates a gradient of chemokines that attract immune cell types, facilitating the progression of tumorigenesis in the distal colon.
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- Combining DNA-demethylating agents (DNMTis) with histone deacetylase inhibitors (HDACis) shows potential for improving cancer immunotherapy, specifically for non-small-cell lung cancer (NSCLC).
- The study investigates the effects and specificities of different HDACis to create an effective low-dose sequential treatment that enhances anti-tumor responses.
- Findings include increased antigen presentation through interferon signaling, reduced MYC signaling, and improved T cell responses in mouse models, supporting a future clinical trial to boost immune checkpoint therapy for NSCLC.
Aberrant silencing of genes by DNA methylation contributes to cancer, yet how this process is initiated remains unclear. Using a murine model of inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment of epigenetic proteins to chromatin, initiating methylation and gene silencing in tumors. Compared with normal epithelium and noninflammation-induced tumors, inflammation-induced tumors gained DNA methylation at CpG islands, some of which are associated with putative tumor suppressor genes.
View Article and Find Full Text PDFBackground: Chronic inflammation and composition of the colon microbiota have been associated with colorectal cancer in humans. The human commensal enterotoxigenic Bacteroides fragilis (ETBF) is linked to both inflammatory bowel disease and colorectal cancer and, in our murine model, causes interleukin 17A (IL-17A)-dependent colon tumors. In these studies, we hypothesized that persistent colonization by ETBF is required for tumorigenesis.
View Article and Find Full Text PDFIt is estimated that the etiology of 20-30% of epithelial cancers is directly associated with inflammation, although the direct molecular events linking inflammation and carcinogenesis are poorly defined. In the context of gastrointestinal disease, the bacterium enterotoxigenic Bacteroides fragilis (ETBF) is a significant source of chronic inflammation and has been implicated as a risk factor for colorectal cancer. Spermine oxidase (SMO) is a polyamine catabolic enzyme that is highly inducible by inflammatory stimuli resulting in increased reactive oxygen species (ROS) and DNA damage.
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