RRecent studies show that gastrointestinal hormones/growth factors may stimulate cell growth by stimulating multiple intracellular tyrosine phosphorylation (TyrP) signaling cascades. However at present little is known about the ability of many gastrointestinal hormones/growth factors to activate these cascades in GI tissues. Our studies have been in two general areas, which include studies of intracellular signaling cascades primarily by tyrosine kinases and studies of tumoral growth attempting to develop novel agents for growth inhibition. Recent studies show that gastrointestinal hormones, similar to growth factors, may stimulate cell growth/cell signaling by stimulating multiple intracellular tyrosine phosphorylation (TyrP) cascades. Whereas these cascades have been extensively investigated with growth factors, little is known in this area with may gastrointestinal hormones. The goal of these studies is to clarify this area primarily concentrating on cholecystokinin receptor cascades and bombesin receptor activation using primarily pancreatic acini as a model natural cell system. Studies involving phosphorylation of PKD1 and GAB1 have been recently completed and during this year a detailed study of the ability of gastrointestinal hormones and growth factors to activate AKT was completed. Studies of PKC theta activation were reported in abstract form and will be completed later this year. The ability of novel cytotoxic sulfur NSAID to alter growth of lung cancer cells was also studied this year.

Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
2009
Total Cost
$457,402
Indirect Cost
City
State
Country
Zip Code
Ramos-Alvarez, Irene; Jensen, R T (2018) P21-activated kinase 4 in pancreatic acinar cells is activated by numerous gastrointestinal hormones/neurotransmitters and growth factors by novel signaling, and its activation stimulates secretory/growth cascades. Am J Physiol Gastrointest Liver Physiol 315:G302-G317
Moreno, Paola; Mantey, Samuel A; Lee, Suk H et al. (2018) A possible new target in lung-cancer cells: The orphan receptor, bombesin receptor subtype-3. Peptides 101:213-226
Moody, Terry W; Ramos-Alvarez, Irene; Jensen, Robert T (2018) Neuropeptide G Protein-Coupled Receptors as Oncotargets. Front Endocrinol (Lausanne) 9:345
Moreno-Villegas, Zaida; Martín-Duce, Antonio; Aparicio, César et al. (2018) Activation of bombesin receptor Subtype-3 by [D-Tyr6,?-Ala11,Phe13,Nle14]bombesin6-14 increased glucose uptake and lipogenesis in human and rat adipocytes. Mol Cell Endocrinol 474:10-19
Moody, Terry W; Ramos-Alvarez, Irene; Moreno, Paula et al. (2017) Endothelin causes transactivation of the EGFR and HER2 in non-small cell lung cancer cells. Peptides 90:90-99
Lee, Lingaku; Ito, Tetsuhide; Nakamura, Taichi et al. (2017) Antifibrotic Effect of Saturated Fatty Acids via Endoplasmic Reticulum Stress Response in Rat Pancreatic Stellate Cells. Pancreas 46:385-394
Ito, Tetsuhide; Jensen, Robert T (2017) Molecular imaging in neuroendocrine tumors: recent advances, controversies, unresolved issues, and roles in management. Curr Opin Endocrinol Diabetes Obes 24:15-24
Moreno, Paola; Ramos-Álvarez, Irene; Moody, Terry W et al. (2016) Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment. Expert Opin Ther Targets 20:1055-73
Moody, Terry W; Nuche-Berenguer, Bernardo; Jensen, Robert T (2016) Vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer. Curr Opin Endocrinol Diabetes Obes 23:38-47
Nakamura, Taichi; Ramos-Álvarez, Irene; Iordanskaia, Tatiana et al. (2016) Molecular basis for high affinity and selectivity of peptide antagonist, Bantag-1, for the orphan BB3 receptor. Biochem Pharmacol 115:64-76

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