BACKGROUND:Regulatory peptide receptors have attracted the interest of oncologists as a new promising approach for cancer pathology,imaging and therapy.Although cholecystokinin (CCK) is a potent modulator of gallbladd...BACKGROUND:Regulatory peptide receptors have attracted the interest of oncologists as a new promising approach for cancer pathology,imaging and therapy.Although cholecystokinin (CCK) is a potent modulator of gallbladder contractility and plays a potential role in pancreatic carcinogenesis through CCK type-A receptor (CCKAR),its role in gallbladder cancer (GBC) is still unknown and immunohistochemical detection of CCKAR in the gallbladder has not yet been reported.This novel case-control study aimed to investigate the expression profile of CCKAR in GBC and gallstone disease (GSD).METHODS:This study included 162 samples of gallbladder:94 from GBC and 68 from GSD.Expression of CCKAR was analyzed by immunohistochemistry and immunoblotting.The results were statistically correlated with disease history including age,sex,presence of gallstone,stage and differentiation.RESULTS:CCKAR was positive in 30/68 (44.1%) of GSD and 72/94 (76.6%) of GBC samples.Fifty-one of the 72 (70.8%) CCKAR-positive GBC samples showed over-expression.Interestingly,consistent results also appeared in the immunoblotting study.CONCLUSIONS:CCKAR expression was significantly increased in GBC compared to GSD.Moreover,CCKAR expression was associated with the degree of tumor differentiation,i.e.,less expression in poorly-differentiated tumors.Thus,it has future prognostic and therapeutic implications in the management of GBC.展开更多
AIM:To investigate the role of caveolin-3(CAV3)and cholecystokinin A receptor(CCKAR)in cholesterol gallstone disease(CGD).METHODS:To establish a mouse model of CGD,male C57BL/6 mice were fed with a lithogenic diet con...AIM:To investigate the role of caveolin-3(CAV3)and cholecystokinin A receptor(CCKAR)in cholesterol gallstone disease(CGD).METHODS:To establish a mouse model of CGD,male C57BL/6 mice were fed with a lithogenic diet containing 1.0%cholic acid,1.25%cholesterol and 15%fat;a similar control group was given a normal diet.The fresh liver weights and liver-to-body weight ratio were compared between the two groups after one month.Serum lipid profile and bile composition were determined with an autoanalyzer.The Cav3 and Cckar mRNA and CAV3and CCKAR protein levels in the liver and gallbladder were determined via real-time polymerase chain reaction and Western blot,respectively.RESULTS:Establishment of the mouse CGD model was verified by the presence of cholesterol gallstones in mice fed the lithogenic diet.Compared with mice maintained on a normal diet,those fed the lithogenic diet had significantly higher mean liver-to-body weight ratio(0.067±0.007 vs 0.039±0.007,P<0.01),serum total cholesterol(4.22±0.46 mmol/L vs 2.21±0.11 mmol/L,P<0.001),bile total cholesterol(1.33±0.33 mmol/L vs 0.21±0.11 mmol/L,P<0.001),and bile phospholipid concentrations(3.55±1.40 mmol/L vs 1.55±0.63 mmol/L,P=0.04),but lower total bile acid concentrations(726.48±51.83μmol/L vs 839.83±23.74μmol/L,P=0.007).The lithogenic diet was also associated with significantly lower CAV3 in the liver and lower CAV3 and CCKAR in the gallbladder compared with the control mice(all P<0.05).CONCLUSION:CAV3 and CCKAR may be involved in cholesterol gallstone disease.展开更多
AIM: To study the interactive relationship of gallbladder motor function, plasma cholecystokinin (CCK) and cholecystokinin A receptor (CCK-R) of gallbladder in patients with cholesterol stone disease.METHODS: Gallblad...AIM: To study the interactive relationship of gallbladder motor function, plasma cholecystokinin (CCK) and cholecystokinin A receptor (CCK-R) of gallbladder in patients with cholesterol stone disease.METHODS: Gallbladder motility was studied by ultrasonography in 33 patients with gallbladder stone and 10 health subjects as controls. Plasma CCK concentration was measured by radioimmunoassay in fasting status (CCK-f) and in 30 min after lipid test meal (CCK-30).Radioligand method was employed to analyze the amount and activity of CCK-R from 33 gallstone patients having cholecystectomy and 8 persons without gallstone died of severe trauma as controls.RESULTS: The percentage of cholesterol in the gallstone composition was more than 70%. The cholesterol stone type was indicated for the patients with gallbladder stone in this study. Based on the criterion of gallbladder residual fraction of the control group, 33 gallstone patients were divided into two subgroups, contractor group (14 cases)and non-contractor group (19 cases), The concentration of CCK-30 was significantly higher in non-contractor group than that in both contractor group and control group (55.86±3.86 pmol/l vs 37.85±0.88 pmol/l and 37.95±0.74 pmol/L, P＜0.01), but there was no difference between contractor group and control group. Meanwhile no significant difference of the concentration of CCK-f could be observed among three groups. The amount of CCK-R was lower in non-contractor group than those in both control group and contractor group (10.27±0.94 fmol/mg vs24.59±2.39 fmol/mg and 22.66±0.55 fmol/mg, P＜0.01).The activity of CCK-R shown as KD in non-contractor group decreased compared to that in control group and contractor group. Only was the activity of CCK-R lower in contractor group than that in control group. The ejection fraction correlated closely with the amount of CCK-R (r = 0.9683,P＜0.01), and the concentration of CCK-30 correlated negatively with the amount of CCK-R closely (r = -0.9627,P＜0.01).CONCLUSION: The distinctive interactive relationship of gallbladder emptying, plasma CCK and CCK-R in gallbladder from this study suggested that the defect of CCK-R may be a key point leading to the impairment of gallbladder motor function and the pathogenesis of cholesterol gallstoneformation may differ in two subgroups of gallstone patient,gallbladder non-contractor group or contractor group.展开更多
with a complex and multifactorial etiology.Declined gallbladder motility reportedly contributes to CG pathogenesis.Furthermore,interstitial Cajal-like cells(ICLCs)are reportedly present in human and guinea pig gallbla...with a complex and multifactorial etiology.Declined gallbladder motility reportedly contributes to CG pathogenesis.Furthermore,interstitial Cajal-like cells(ICLCs)are reportedly present in human and guinea pig gallbladder tissue.ICLCs potentially contribute to the regulation of gallbladder motility,and aberrant conditions involving the loss of ICLCs and/or a reduction in its pacing potential and reactivity to cholecystokinin may promote CG pathogenesis.This review discusses the association between ICLCs and CG pathogenesis and provides a basis for further studies on the functions of ICLCs and the etiologies of CG.展开更多
基金supported by a grant from the Indian Council of Medical Research(ICMR Project Ref No.3/2/2/187/2009/NCD-Ⅲ)
文摘BACKGROUND:Regulatory peptide receptors have attracted the interest of oncologists as a new promising approach for cancer pathology,imaging and therapy.Although cholecystokinin (CCK) is a potent modulator of gallbladder contractility and plays a potential role in pancreatic carcinogenesis through CCK type-A receptor (CCKAR),its role in gallbladder cancer (GBC) is still unknown and immunohistochemical detection of CCKAR in the gallbladder has not yet been reported.This novel case-control study aimed to investigate the expression profile of CCKAR in GBC and gallstone disease (GSD).METHODS:This study included 162 samples of gallbladder:94 from GBC and 68 from GSD.Expression of CCKAR was analyzed by immunohistochemistry and immunoblotting.The results were statistically correlated with disease history including age,sex,presence of gallstone,stage and differentiation.RESULTS:CCKAR was positive in 30/68 (44.1%) of GSD and 72/94 (76.6%) of GBC samples.Fifty-one of the 72 (70.8%) CCKAR-positive GBC samples showed over-expression.Interestingly,consistent results also appeared in the immunoblotting study.CONCLUSIONS:CCKAR expression was significantly increased in GBC compared to GSD.Moreover,CCKAR expression was associated with the degree of tumor differentiation,i.e.,less expression in poorly-differentiated tumors.Thus,it has future prognostic and therapeutic implications in the management of GBC.
基金Supported by National Natural Science Foundation of China,No.81070366
文摘AIM:To investigate the role of caveolin-3(CAV3)and cholecystokinin A receptor(CCKAR)in cholesterol gallstone disease(CGD).METHODS:To establish a mouse model of CGD,male C57BL/6 mice were fed with a lithogenic diet containing 1.0%cholic acid,1.25%cholesterol and 15%fat;a similar control group was given a normal diet.The fresh liver weights and liver-to-body weight ratio were compared between the two groups after one month.Serum lipid profile and bile composition were determined with an autoanalyzer.The Cav3 and Cckar mRNA and CAV3and CCKAR protein levels in the liver and gallbladder were determined via real-time polymerase chain reaction and Western blot,respectively.RESULTS:Establishment of the mouse CGD model was verified by the presence of cholesterol gallstones in mice fed the lithogenic diet.Compared with mice maintained on a normal diet,those fed the lithogenic diet had significantly higher mean liver-to-body weight ratio(0.067±0.007 vs 0.039±0.007,P<0.01),serum total cholesterol(4.22±0.46 mmol/L vs 2.21±0.11 mmol/L,P<0.001),bile total cholesterol(1.33±0.33 mmol/L vs 0.21±0.11 mmol/L,P<0.001),and bile phospholipid concentrations(3.55±1.40 mmol/L vs 1.55±0.63 mmol/L,P=0.04),but lower total bile acid concentrations(726.48±51.83μmol/L vs 839.83±23.74μmol/L,P=0.007).The lithogenic diet was also associated with significantly lower CAV3 in the liver and lower CAV3 and CCKAR in the gallbladder compared with the control mice(all P<0.05).CONCLUSION:CAV3 and CCKAR may be involved in cholesterol gallstone disease.
基金Supported by the Science Development Foundation of Shanghai,No. 95411902
文摘AIM: To study the interactive relationship of gallbladder motor function, plasma cholecystokinin (CCK) and cholecystokinin A receptor (CCK-R) of gallbladder in patients with cholesterol stone disease.METHODS: Gallbladder motility was studied by ultrasonography in 33 patients with gallbladder stone and 10 health subjects as controls. Plasma CCK concentration was measured by radioimmunoassay in fasting status (CCK-f) and in 30 min after lipid test meal (CCK-30).Radioligand method was employed to analyze the amount and activity of CCK-R from 33 gallstone patients having cholecystectomy and 8 persons without gallstone died of severe trauma as controls.RESULTS: The percentage of cholesterol in the gallstone composition was more than 70%. The cholesterol stone type was indicated for the patients with gallbladder stone in this study. Based on the criterion of gallbladder residual fraction of the control group, 33 gallstone patients were divided into two subgroups, contractor group (14 cases)and non-contractor group (19 cases), The concentration of CCK-30 was significantly higher in non-contractor group than that in both contractor group and control group (55.86±3.86 pmol/l vs 37.85±0.88 pmol/l and 37.95±0.74 pmol/L, P＜0.01), but there was no difference between contractor group and control group. Meanwhile no significant difference of the concentration of CCK-f could be observed among three groups. The amount of CCK-R was lower in non-contractor group than those in both control group and contractor group (10.27±0.94 fmol/mg vs24.59±2.39 fmol/mg and 22.66±0.55 fmol/mg, P＜0.01).The activity of CCK-R shown as KD in non-contractor group decreased compared to that in control group and contractor group. Only was the activity of CCK-R lower in contractor group than that in control group. The ejection fraction correlated closely with the amount of CCK-R (r = 0.9683,P＜0.01), and the concentration of CCK-30 correlated negatively with the amount of CCK-R closely (r = -0.9627,P＜0.01).CONCLUSION: The distinctive interactive relationship of gallbladder emptying, plasma CCK and CCK-R in gallbladder from this study suggested that the defect of CCK-R may be a key point leading to the impairment of gallbladder motor function and the pathogenesis of cholesterol gallstoneformation may differ in two subgroups of gallstone patient,gallbladder non-contractor group or contractor group.
基金National Natural Science Foundation of China,No.81000183and Natural Science Foundation of Liaoning Province,No.20180550125.
文摘with a complex and multifactorial etiology.Declined gallbladder motility reportedly contributes to CG pathogenesis.Furthermore,interstitial Cajal-like cells(ICLCs)are reportedly present in human and guinea pig gallbladder tissue.ICLCs potentially contribute to the regulation of gallbladder motility,and aberrant conditions involving the loss of ICLCs and/or a reduction in its pacing potential and reactivity to cholecystokinin may promote CG pathogenesis.This review discusses the association between ICLCs and CG pathogenesis and provides a basis for further studies on the functions of ICLCs and the etiologies of CG.
