The present study reports the first evidence that the gastrointestinal peptide gastrin stimulates the growth of several human pancreatic cancer cells in culture and in tumors transplanted to nude mice. Gastrin promoted growth of all cell lines tested at a dose comparable to the binding affinity, providing evidence for a physiologically relevant receptor. The stimulatory effects of gastrin were blocked by the CCK-B/gastrin receptor antagonist L-365,260 and not by the CCK-A receptor antagonist L-364,718. Growth of PANC-1 cells in culture were inhibited by L-365,260, suggesting that gastrin is tonically produced by PANC-1 cells for regulation of growth. Athymic nude mice bearing PANC-1 xenografts were treated for 24 days subcutaneously with either 1% bovine serum albumin (diluent), pentagastrin (1 mg/kg), or L-365,260 (1 mg/kg) twice daily. Tumors from the pentagastrin-treated mice were found to weigh more and have greater protein and DNA content than controls, whereas these values were all decreased in tumors of L-365,260-treated mice. Receptor binding capacity changed in tumors of animals treated with the peptide or antagonist, suggesting a regulatory process. Gastrin immunoreactivity was detected in a transplanted PANC-1 human tumor. These results identify gastrin as a potent trophic peptide that actively stimulates growth of human pancreatic cancer and does so through a CCK-B/gastrin-like receptor.
Venlafaxine hydrochloride is a novel bicyclic antidepressant which inhibits the reuptake of serotonin, norepinephrine and, to a lesser extent, dopamine. A 41-year-old female ingested 4.5 g venlafaxine, 500 mg diphenhydramine, 50 mg thiothixene and subsequently experienced severe central nervous system depression requiring intubation. She also developed elevated systolic and diastolic blood pressures and sinus tachycardia. The patient was decontaminated with gastric lavage and activated charcoal. She regained consciousness within a few hours and was extubated nine hours after ingestion. This case demonstrates that severe central nervous system depression may follow venlafaxine overdose.
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