gastrins and Wilms-Tumor

The role of gastrin in the control of growth of renal G401 cells isolated from a human nephroblastoma (Wilms' tumour) was investigated. G401 cell growth was enhanced in the presence of exogenous gastrin. Addition of anti-gastrin antibodies to serum-free medium significantly inhibited the growth of G401 cells. G401 cells contained the equivalent of 4.3 pg/10(6) cells of gastrin, and serum-free medium collected over 48 hr from G401 cells contained the equivalent of 38 ng/10(6) cells of gastrin, as determined by radioimmunoassay. Growth of G401 cells was inhibited in a concentration-related way by a variety of gastrin/CCK receptor antagonists. Devazepide and proglumide were, respectively, the most and the least potent inhibitors of G401 cell growth (potency order devazepide > L-365,260 = lorglumide > loxiglumide > benzotript > proglumide). These gastrin/CCK receptor antagonists had similar growth-inhibitory activities in human colonic adenocarcinoma HCT-116 cells. Growth of HCT-116 cells was stimulated to a lesser extent, as compared with G401 cells, by exogenous gastrin, and endogenous gastrin was not detectable in HCT-116 cells. The results are consistent with a role for a gastrin-like peptide in the control of growth of a renal cell line. The data suggest that gastrin/CCK receptor antagonists warrant further investigation as therapeutic agents for the control of gastrin-responsive tumours derived from outside, as well as inside, the gastrointestinal tract, including tumours derived from the kidney.

Topics: Benzamides; Benzodiazepinones; Cell Division; Devazepide; Gastrins; Humans; Indoles; Kidney Neoplasms; Meglumine; Phenylurea Compounds; Proglumide; Receptors, Cholecystokinin; Tumor Cells, Cultured; Wilms Tumor

Genitourinary anomalies were looked for in patients with congenital hypertrophic pyloric stenosis. In a prospective series of 64 patients investigated by intravenous pyelography, 13 were abnormal (20.6%). In a retrospective series of 232 patients, 6 had anomalies of the upper urinary tract (2.7%). In this latter series the incidence of inguinal hernia (3.4%), undescended testes (3.0%), and hypospadias (0.9%) was determined. In another 10 patients urinary tract anomalies (5), urinary infection (2), and a significant family history (3) were found associated with congenital pyloric stenosis. As the incidence of these anomalies is greater than expected, which suggests an interrelationship, a hypothesis has been proposed linking genetic factors and the metabolism of gastrin with the etiology of congenital hypertrophic pyloric stenosis.

Topics: Female; Gastrins; Hernia, Inguinal; Humans; Hypertrophy; Kidney Neoplasms; Male; Prospective Studies; Pyloric Stenosis; Retrospective Studies; Urogenital Abnormalities; Wilms Tumor