Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secretin plays an important role in the growth regulation of certain cancers in vitro. The nude mouse is a suitable model for evaluation of the effects of this hormone on tumor xenografts in vivo, but little is known about long-term actions of secretin in this species. We investigated the impact of chronically administered synthetic porcine secretin in the nude mouse. Six groups of mice (eight animals each) received twice-daily intraperitoneal injections of saline or secretin at 0.5, 5, 50, 500, or 5,000 micrograms/kg for 14 days. Body weight and general health were unaffected by exogenous secretin, and no apparent behavioral effects were observed. Seven abdominal organs were examined at necropsy and all were histologically normal. The only organ that showed a weight change was the pancreas (13% decrease at the highest secretin dose). This was accompanied by decreases in DNA and RNA content, indicating pancreatic hypoplasia. Secretin administration caused changes in DNA and/or RNA content (but not protein content or weight) in liver, small bowel, cecum, and large bowel. No effect of secretin on stomach or kidney was observed. Our work demonstrates the safety of frequent injections of pharmacologic doses of secretin in this frail animal and suggests that the nude mouse is an appropriate model for the in vivo study of tumor growth regulation by secretin.
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PMID:Effect of chronically-administered secretin on the nude mouse. 245 59

We have examined the ability of a number of neuropeptides to increase tyrosine hydroxylase (TH) activity in the superior cervical ganglion in vitro. Secretin and vasoactive intestinal peptide (VIP) both increased TH activity, whereas angiotensin II, bombesin, bradykinin, cholecystokinin octapeptide, insulin, luteinizing hormone-releasing hormone, [D-Ala2, Met5]enkephalinamide, motilin, neurotensin, somatostatin, and substance P produced no effects. Secretin and VIP increased TH activity with an EC50 of 5 nM and 0.5 microM, respectively. The effects of these peptides were not altered by prior decentralization of the ganglia, by addition of hexamethonium (3 mM) and atropine (6 microM), or by lowering the concentration of calcium in the medium to 0.1 mM. Addition of carbachol (3 microM) potentiated the effects of both secretin and VIP on TH activity. Several gastrointestinal peptides with structural similarities to secretin and VIP were examined for their ability to increase TH activity. Glucagon, gastric inhibitory peptide and human pancreatic tumor growth hormone-releasing factor produced no effect at a concentration of 10 microM, while PHI increased enzyme activity.
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PMID:Acute stimulation of ganglionic tyrosine hydroxylase activity by secretin, VIP and PHI. 614 16

Secretin receptors that are key for regulation of healthy pancreatic ductal epithelial cells have been reported to be functionally absent on ductal pancreatic adenocarcinomas. Here, we examine the possible presence and function of molecular forms of the secretin receptor in pancreatic cancer cell lines and in primary tumors. Surprisingly, reverse transcription-PCR and sequencing demonstrated wild-type secretin receptor mRNA in each of four cell lines and three primary tumors. Lack of biological response to nanomolar concentrations of secretin was best explained by the demonstrated coexpression of a second and predominant transcript in each of the cell lines and tumors. This represented a variant of the secretin receptor in which the third exon was spliced out to eliminate residues 44-79 from the NH(2)-terminal tail. This spliceoform has only recently been recognized in a rare gastrinoma, where it was incapable of binding secretin or signaling, and possessed dominant-negative activity to suppress hormone action at the wild-type secretin receptor (1). Overexpression of wild-type secretin receptor in Panc-1 cells driven by transfection of fully processed cDNA resulted in normal responsiveness to low concentrations of secretin, establishing the ability of these cells to produce a receptor capable of normal biosynthesis, trafficking, and signaling. Bioluminescence resonance energy transfer demonstrated that the variant receptor could form a heterodimer with wild-type receptor, providing a molecular mechanism for its dominant-negative activity. This suggests that missplicing is responsible for expression of a secretin receptor variant having the ability to suppress the function of wild-type receptor by a direct interaction. In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays in receptor-bearing Chinese hamster ovary cells, the secretin receptor was shown to have growth-inhibitory effects. Suppression of this activity in pancreatic carcinoma might, therefore, facilitate tumor growth and progression of this aggressive neoplasm.
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PMID:Silencing of secretin receptor function by dimerization with a misspliced variant secretin receptor in ductal pancreatic adenocarcinoma. 1223 88