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Combination Oral Immunotherapy With Il-10 And Il-12 Effectively Treats Colon Tumors Via Synergistic Effects On Il-17 Producing T Cells And Colon Epithelial Barrier Integrity., Neal Bhutiani Aug 2018

Combination Oral Immunotherapy With Il-10 And Il-12 Effectively Treats Colon Tumors Via Synergistic Effects On Il-17 Producing T Cells And Colon Epithelial Barrier Integrity., Neal Bhutiani

Electronic Theses and Dissertations

In this dissertation, the relationship between colon cancer and inflammation, the utility of novel imaging modalities for diagnosis of colitis and cancer, and the therapeutic efficacy of orally delivered, particle-based immunotherapy for the treatment of colon cancer are evaluated. In Chapters One and Two, multispectral optoacoustic tomography (MSOT) is demonstrated to effectively detect colon inflammation without the use of exogenous contrast prior to detection using conventional colonoscopy. Oral particle uptake is demonstrated in the distal small intestine and proximal colon, confirming site-specific delivery. In Chapter Three, administration of IL-10 and IL-12 containing particles is shown to act synergistically to significantly …


Inflammasome Independent Leukotriene-B4 Production Drives Crystalline Silica Induced Sterile Inflammation., Bindu Hegde May 2018

Inflammasome Independent Leukotriene-B4 Production Drives Crystalline Silica Induced Sterile Inflammation., Bindu Hegde

Electronic Theses and Dissertations

Silicosis is an irreversible lung inflammatory disease caused by chronic exposure to crystalline silica (CS) and is one of the most prevalent occupational diseases worldwide. Lipid chemoattractant Leukotriene B4 (LTB4) plays an important role in neutrophilic inflammation that drives silicosis and promotes lung cancer. Previous studies in our laboratory have demonstrated that CS-induced neutrophilic inflammation and lung tumor burden in K-rasLA1 mice is abrogated in the LTB4-receptor deficient mice. Another pathway whose importance is well studied in the progression of silicosis is the Nalp3 inflammasome pathway. Studies have shown inflammasome- dependent IL-1b to be …