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52. Teaching and Learning Faulkner in the Digital Age

Author

Albert-Tate, Haley, Bryant, Taylor, Hayes, Jonathan, Mills, Nikki Magaziner, Towner, Theresa, Albert-Tate, Haley, Bryant, Taylor, Hayes, Jonathan, Mills, Nikki Magaziner, and Towner, Theresa

53. Teaching and Learning Faulkner in the Digital Age

Author

Albert-Tate, Haley, Bryant, Taylor, Hayes, Jonathan, Mills, Nikki Magaziner, Towner, Theresa, Albert-Tate, Haley, Bryant, Taylor, Hayes, Jonathan, Mills, Nikki Magaziner, and Towner, Theresa

56. EXIT WEST.

Author

BRYANT, TAYLOR

Published
2017

57. Loss of natural killer T cells promotes pancreatic cancer in LSL-Kras G12D/+ mice.

Author

Janakiram NB, Mohammed A, Bryant T, Ritchie R, Stratton N, Jackson L, Lightfoot S, Benbrook DM, Asch AS, Lang ML, and Rao CV

Subjects
Animals, Antigens, CD1d genetics, Arachidonate 5-Lipoxygenase immunology, Arachidonate 5-Lipoxygenase metabolism, CD8 Antigens immunology, CD8 Antigens metabolism, Carcinoma in Situ genetics, Carcinoma in Situ metabolism, Carcinoma in Situ prevention & control, Cell Proliferation, Disease Progression, Genes, ras, Genetic Predisposition to Disease, Humans, Lipoxygenase Inhibitors pharmacology, Macrophages drug effects, Macrophages metabolism, Mice, Inbred C57BL, Mice, Knockout, Natural Killer T-Cells metabolism, Neoplastic Stem Cells immunology, Neoplastic Stem Cells pathology, Pancreatic Neoplasms genetics, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms prevention & control, Phenotype, Prostaglandin-E Synthases antagonists & inhibitors, Prostaglandin-E Synthases immunology, Prostaglandin-E Synthases metabolism, Signal Transduction, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Time Factors, Carcinoma in Situ immunology, Macrophages immunology, Natural Killer T-Cells immunology, Pancreatic Neoplasms immunology
Abstract

The role of the unique T-cell population, natural killer T (NKT) cells, which have similar functions to NK cells in pancreatic cancer (PC), is not yet evaluated. To address the regulatory roles of NKT cells on tumour progression through tumour-associated macrophages (TAM) and their production of microsomal prostaglandin E synthase-1 (mPGES-1) and 5-lipoxygenase (5-LOX) in (Kras)-driven pancreatic tumour (KPT) progression, we crossed CD1d -/- mice deficient in both invariant and variant NKT cells with the Kras G12D mice. Loss of NKT cells significantly increased pancreatic intraepithelial neoplasia (PanIN) lesions and also increased 5-LOX and mPGES-1 expression in M2-type macrophages and cancer stem-like cells in pancreatic tumours. Pharmacological inhibition of mPGES-1 and 5-LOX in M2 macrophages with specific inhibitor YS-121 in KPT-CD1d -/- mice decreased PanIN lesions and suppressed tumour growth in association with elevated levels of active CD8a cells. Hence, NKT cells regulate PC by modulating TAMs (M2) through mPGES-1 and 5-LOX; and the absence of NKT cells leads to aggressive development of PC., (© 2017 John Wiley & Sons Ltd.)

Published
2017
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