gastrin-17 and Liver-Neoplasms

To determine whether human liver cells respond to gastrin peptides by reducing their secretion of triacylglycerols, as recently observed in rat hepatocytes.. Cells of the human hepatoblastoma cell line Hep G2 were incubated with pentagastrin and heptadeca gastrin, followed by lipid analysis of media and cells.. Cultivation of cells; analyses of triacylglycerols, cholesterol and protein; statistical analysis.. As the secretion of triacylglycerols in Hep G2 cells incubated with basal medium (Eagle's minimum essential medium with non-essential amino acids, penicillin, streptomycin and glutamine) is only about 20% of the triacylglycerol secretion reported for human liver cells, the possibility of detecting statistically significant effects of gastrin peptides on lipid secretion is reduced compared to the situation in normal hepatocytes. However, by a combined addition of 0.1 mmol/l albumin-bound oleate, 10 mmol/l sodium butyrate and 0.1 mg/ml dextran sulphate to the basal medium, the triacylglycerol secretion in Hep G2 cells was found to be more than twice as high as in cells incubated with basal medium alone. With this supplemented medium a biphasic concentration-dependent statistically significant inhibitory effect of both pentagastrin and heptadeca gastrin on triacylglycerol secretion in Hep G2 cells was demonstrated.. These results indicate that gastrin peptides may play a role in the regulation of lipoprotein secretion in human liver cells.

Topics: Culture Media; Gastrins; Hormones; Humans; Liver; Liver Neoplasms; Pentagastrin; Triglycerides; Tumor Cells, Cultured

Forty-six patients with the gastrinoma syndrome were divided into 2 categories: 1) benign sporadic gastrinoma (n = 30), and 2) gastrinoma with metastases to liver (n = 16). Thirteen of the 46 patients had multiple endocrine neoplasia type I syndrome. Serum gastrin levels in patients fasted overnight were determined by RIA using antisera directed toward the NH2- and COOH-terminals of heptadecapeptide gastrin (G17) and the NH2-terminus of the triacontatetrapeptide (G34). These results were compared with findings in 50 normal subjects. In the normal subjects, the mean COOH-terminal gastrin-17 level was higher [65 +/- 8 (+/- SEM) pg/ml] than the NH2-terminal gastrin-17 level (11 +/- 0.2 pg/ml) and lower than the NH2-terminal gastrin-34 level (134 +/- 20 pg/ml). The levels of NH2-terminal gastrin-17 were higher in patients with metastatic disease than in those with benign gastrinoma, whereas the COOH-terminal gastrin-17 and the NH2-terminal gastrin-34 levels were similarly high in both groups. The mean ratio of NH2-terminal gastrin-17 to COOH-terminal gastrin-17 was less than 1 in normal subjects (0.22 +/- 0.02) and benign gastrinoma patients (0.2 +/- 0.04), and it was 2.2 +/- 0.41 in the patients with metastatic gastrinoma. An NH2 to COOH gastrin-17 ratio greater than 1 was found in 13 of 16 patients with metastatic gastrinoma, but in none of the patients with benign gastrinoma or normal subjects. Similar results were found in multiple endocrine neoplasia type I patients with benign and metastatic disease. A high NH2 to COOH gastrin-17 ratio is suggestive of metastatic gastrinoma. In 4 patients with metastatic gastrinoma, the NH2 to COOH gastrin-17 ratio fell in parallel with the response to chemotherapy.

Topics: Chromatography, Gel; Gastrins; Humans; Liver Neoplasms; Multiple Endocrine Neoplasia; Protein Precursors; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Chromatography, Ion Exchange; Gastrins; Humans; Liver Neoplasms; Prognosis; Radioimmunoassay; Zollinger-Ellison Syndrome