cholecystokinin and Gallbladder-Neoplasms

Cholecystokinin is present in abundance in gallbladder tissue and mediates function through two structurally related receptors, CCK1R and CCK2R. Heterodimerization of these receptors is known to impact cell growth in vitro. However, the significance of these heterodimers in gallbladder carcinogenesis is relatively unknown.. Therefore, we evaluated the expression and the dimerization status of CCK1 and CCK2 receptors in human gallbladder carcinoma cell line (GBC-SD) and resected gallbladder tissue from normal (n = 10), cholelithiasis (n = 25) and gallbladder cancer (n = 25) by immunofluorescence/immunohistochemistry and western blot. The dimerization status of CCK1R and CCK2R was evaluated by co-immunoprecipitation. To understand the effect of heterodimerization of these receptors on growth-related signaling pathways, the expression of p-AKT, rictor, raptor and p-ERK was evaluated by western blot.. We demonstrated the expression and heterodimerization of CCK1 and CCK2 receptor in GBC-SD gall bladder carcinoma cell line. Knockdown of CCK1R and CCK2R in the cell line led to significant reduction in p-AKT (P = 0.005; P = 0.0001) and rictor (P < 0.001; P < 0.001) levels. In tissue samples, significantly higher expression of CCK1R and CCK2R was observed in gallbladder cancer when compared to other groups both by immunohistochemistry (P = 0.008 and P = 0.013) and western blot (P = 0.009 and P = 0.003). An increase in heterodimer formation of CCK1R with CCK2R was observed in gallbladder cancer when compared to normal and cholelithiasis tissues. No significant difference in the expression of p-AKT and p-ERK was observed between the three groups.. Our results provide the first evidence of heterodimerization of CCK1R and CCK2R in gallbladder tissue, and its association with development of gallbladder cancer. This finding has potential clinical and therapeutic significance.

Topics: Carcinogenesis; Carcinoma in Situ; Cholecystokinin; Dimerization; Gallbladder Neoplasms; Humans; Proto-Oncogene Proteins c-akt; Receptor, Cholecystokinin B

The aim of this study was to examine whether the type of bilioenterostomy enhances biliary carcinogenesis in the hamster model. Syrian hamsters were divided into the following groups; simple laparotomy (control group), cholecystoduodenostomy with dissection of the extrahepatic bile duct on the distal end of the common duct (CDDB group) and cholecystoileostomy with dissection of the extrahepatic bile duct on the distal end of the common duct (CIDB group). Following these procedures, all hamsters received N-nitrosobis(2-oxopropyl)amine. The diameter of the extrahepatic bile duct and plasma levels of cholecystokinin (CCK) were measured and the number of neoplastic lesions was counted microscopically. Proliferative effect of the procedures on the biliary epithelium was examined by proliferative cell nuclear antigen. In the CDDB group the extrahepatic bile duct was significantly dilated and carcinogenesis of the gall-bladder and extrahepatic bile ducts was enhanced. In the CIDB group the CCK bioactivity was stimulated and intrahepatic biliary duct, but not gall bladder and extrahepatic bile duct, carcinogenesis was promoted more than that observed in the CDDB group. Proliferation of the biliary duct epithelium was enhanced in both the CDDB and CIDB groups. Cholecystoduodenostomy enhanced intra- and extrahepatic bile duct carcinoma, whereas cholecystoileostomy promoted only intrahepatic bile duct carcinoma. Some factors in the intestinal juice seem to play a role in the promotion of biliary tract carcinoma.

Topics: Animals; Bile Duct Neoplasms; Bile Ducts; Bile Ducts, Extrahepatic; Biliary Tract; Biliary Tract Neoplasms; Carcinogens; Carcinoma, Papillary; Cell Division; Cholecystokinin; Cricetinae; Epithelium; Female; Gallbladder; Gallbladder Neoplasms; Ileum; Mesocricetus; Nitrosamines; Proliferating Cell Nuclear Antigen

The influence of intraduodenal bile deficiency due to chronic bile duct obstruction and acute exogenous administration of bile acids on plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) was investigated. Fourteen patients with tumor-induced bile duct stenosis and five healthy volunteers were given a liquid test meal. Four of the patients had a simultaneous pancreatic duct stenosis. On another day 4 g chenodeoxycholic acid were administered concomitantly with the liquid test meal in six of the patients and all controls. Basal and meal-stimulated plasma CCK did not differ between patients and controls. A pancreatic duct stenosis, which was associated with diminished plasma PP concentrations, had no influence on plasma CCK release. Exogenous bile acids significantly reduced the postprandial CCK response in both groups. Bile-induced inhibition was significantly greater in patients than in controls (75 +/- 7% and 44 +/- 11%, respectively; p less than 0.05). It is concluded that intraduodenal bile is an important modulator of the postprandial secretory activity of the CCK cell. Although chronic intraduodenal bile acid reduction in tumor-induced biliary duct stenosis did not influence plasma CCK levels, a negative feedback control of plasma CCK by acute bile acid administration could be demonstrated.

Topics: Adult; Aged; Bile Acids and Salts; Biliary Tract Neoplasms; Cholecystokinin; Cholestasis; Feedback; Gallbladder Neoplasms; Humans; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide

The cholecystokinin cholescintigraphic findings of fundal adenomyomatosis in a 29-yr-old male with severe post-prandial pain are presented. Planar cholescintigraphy demonstrated a trilobed gallbladder contour. Following the administration of 0.02 micrograms/kg of cholecystokinin at maximal gallbladder filling, fundal dyskinesia was observed. Regional gallbladder ejection fractions were: whole gallbladder, 43%; proximal two-thirds of the gallbladder, 70%; and gallbladder fundus, 32%. First harmonic Fourier phase and amplitude images demonstrated: (a) decreased fundal amplitude values, and (b) a phase shift of the pixels in the gallbladder fundus.

Topics: Adult; Cholecystokinin; Endometriosis; Gallbladder; Gallbladder Neoplasms; Humans; Imino Acids; Male; Organometallic Compounds; Peristalsis; Radionuclide Imaging; Technetium Tc 99m Disofenin

Topics: Angiography; Bile Duct Neoplasms; Celiac Artery; Cholecystokinin; Gallbladder Neoplasms; Hepatic Artery; Humans; Mesenteric Arteries; Pancreatic Neoplasms

Topics: Adolescent; Cholecystectomy; Cholecystokinin; Endometriosis; Female; Gallbladder Neoplasms; Humans