<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "PI3K/AKT signaling is essential for\r\ncommunication between tissue infiltrating mast\r\ncells, macrophages, and epithelial cells in colitis-induced\r\ncancer"^^ . "Colorectal cancer is one of the leading cause of mortality in USA and worldwide.\r\nColon cancer is a complex world of connective tissue epithelial, inflammatory and\r\nendothelial cell interactions. It s long known that patients with persistent colitis\r\nare at high risk of developing colon cancer, where the patients passes through a\r\nphase from colitis to colitis induced dysplasia and finally invasive cancer. Though\r\na lot of efforts have been poured into understanding the mechanisms underlying\r\nthe etiology of colon cancer, less has been known with respect to the changes\r\nhappening at genomic and proteomic levels in the inflammatory compartment of\r\nthe colon cancer with respect to interaction with the tumor epithelium and\r\nsubsequent tumor progression.\r\nIt is well known that the levels of PI3K/AKT and inflammatory cells mainly mast\r\ncells and macrophages are upregulated in the cancer. However, few efforts have\r\nbeen done to understand the pathogenesis in this direction, but they lacked in the\r\ncorrelative study of PI3K/AKT or immune infiltration in colon cancer or colitis and\r\ntheir spatial distribution with respect to cancer prognosis. Hence for the first time\r\nin this study a novel investigation was conducted where human patients were\r\nstudied in the various stages of inflammation associated colonic illness i.e. colitis\r\nto dysplasia and invasive cancer and compared it to normal amongst\r\nthemselves. The human-patient colonic tissue specimens were investigated for\r\nthe spatial distribution of mast cells, macrophages and pAKT in the histological\r\nareas of musoca and submucosa. It was observed that mast cells, macrophages\r\nand pAKT levels incrementally rise from colitis to dysplasia to cancer in the\r\nsubmucosal tissues. In mucosal tissue, pAKT levels were found atleast 10 fold\r\nhigher in the stromal cells in comparison with epithelial cells. The stromal and\r\nsubmucosal pAKT+ cells were found to be the macrophages that progressively\r\ninfiltrate from colitis to dysplasia and invasive cancer, also mast cells were found\r\nto be high in pAKT activity.\r\nTo investigate the role of PI3K/AKT in mast cells and macrophages biology and\r\n4\r\ntheir crosstalk with colonic epithelium a pan PI3K/AKT inhibitor used in clinical\r\ntrials “LY2949002” was used. PI3K/AKT in mast cells was found to be critical for\r\nperipheral blood isolated human macrophage migration. LY294002 treatment of\r\nhuman and gut-derived murine mast cells restricted their ability to degranulate in\r\ndose-dependent manner. Moreover, inhibition of PI3K/AKT in human and mouse\r\nmast cells blocked the release of growth factors from them, and attenuated tumor\r\nproliferation and invasion promoting properties of mast cells. Also, PI3K/AKT\r\ninhibition in tumor infiltrating leukocytes isolated from colitis-associated patients\r\nlowered their soluble growth factor and cell-cell contact based tumor invasion\r\npromoting properties.\r\nTreatment of LY294002 using intra-peritoneal injections lowered the incidence of\r\ncolitis associated invasive cancer development by day 56 in the Piroxicam\r\ntreated IL-10-/- mice. LY294002 displayed a striking effect on the epithelial\r\nproliferation, induced tumor apoptosis and attenuated the pAKT levels.\r\nLY294002 showed special predilection for the pAKT+ stromal cells in comparison\r\nwith pAKT+ epithelial cells. Moreover, frequencies of mast cells and granulocytebased\r\ninflammation were lowered after LY294002 treatment. Finally, the in situ\r\ndegraunulating potential of mast cells was attenuated by LY294002 treatment.\r\nIn conclusion, using in situ human patient specimen study, in vitro human and\r\nmurine assays and in vivo mouse model system this study confirms the role of\r\nPI3K/AKT pathway in mast cells and tumor infiltrating leukocytes in crosstalk with\r\nthe colonic epithelium and progression of colonic tissue from colitis."^^ . "2013" . . . . . . . "Mohammad Wasim Kayyum"^^ . "Khan"^^ . "Mohammad Wasim Kayyum Khan"^^ . . . . . . "PI3K/AKT signaling is essential for\r\ncommunication between tissue infiltrating mast\r\ncells, macrophages, and epithelial cells in colitis-induced\r\ncancer (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "PI3K/AKT signaling is essential for\r\ncommunication between tissue infiltrating mast\r\ncells, macrophages, and epithelial cells in colitis-induced\r\ncancer (PDF)"^^ . . . "PhD thesis complete.pdf"^^ . . . "PI3K/AKT signaling is essential for\r\ncommunication between tissue infiltrating mast\r\ncells, macrophages, and epithelial cells in colitis-induced\r\ncancer (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "PI3K/AKT signaling is essential for\r\ncommunication between tissue infiltrating mast\r\ncells, macrophages, and epithelial cells in colitis-induced\r\ncancer (Other)"^^ . . . . . . "preview.jpg"^^ . . . "PI3K/AKT signaling is essential for\r\ncommunication between tissue infiltrating mast\r\ncells, macrophages, and epithelial cells in colitis-induced\r\ncancer (Other)"^^ . . . . . . "medium.jpg"^^ . . . "PI3K/AKT signaling is essential for\r\ncommunication between tissue infiltrating mast\r\ncells, macrophages, and epithelial cells in colitis-induced\r\ncancer (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #14917 \n\nPI3K/AKT signaling is essential for \ncommunication between tissue infiltrating mast \ncells, macrophages, and epithelial cells in colitis-induced \ncancer\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .