Gallbladder cancer(GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment op...Gallbladder cancer(GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment options. These necessitate development of early prognostic/predictive markers and novel therapeutic interventions. Micro RNAs(mi RNAs) are small, noncoding RNA molecules that play a key role in tumor biology by functioning like tumor suppressor- or oncogenes and their aberrant expression are associated with the pathogenesis of several neoplasms with overwhelming clinical implications. Since mi RNA signature is tissue specific, here, we focused on current data concerning the mi RNAs abberations in GBC pathogenesis. In GBC, mi RNAs with tumor suppressor activity(mi R-135-5p, mi R-335, mi R-34 a, mi R-26 a, mi R-146b-5p, Mir-218-5p, mi R-1, mi R-145, mir-130a) were found downregulated, while those with oncogenic property(mi R-20 a, mi R-182, mir-155) were upregulated. The expression profile of mi RNAs was significantly associated with GBC prognosis and prediction, and forced over-expression/ inhibition of these mi RNAs was shown to affect tumor growth and development. Further, differential expression of mi RNAs in the blood samples of GBC patients suggest mi RNAs as promising noninvasive biomarker. Thus, mi RNAs represent potential candidate for GBC management, though many hurdles need to be overcome before mi RNAs therapy can be clinically applied to GBC prevention and treatment.展开更多
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
文摘Gallbladder cancer(GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment options. These necessitate development of early prognostic/predictive markers and novel therapeutic interventions. Micro RNAs(mi RNAs) are small, noncoding RNA molecules that play a key role in tumor biology by functioning like tumor suppressor- or oncogenes and their aberrant expression are associated with the pathogenesis of several neoplasms with overwhelming clinical implications. Since mi RNA signature is tissue specific, here, we focused on current data concerning the mi RNAs abberations in GBC pathogenesis. In GBC, mi RNAs with tumor suppressor activity(mi R-135-5p, mi R-335, mi R-34 a, mi R-26 a, mi R-146b-5p, Mir-218-5p, mi R-1, mi R-145, mir-130a) were found downregulated, while those with oncogenic property(mi R-20 a, mi R-182, mir-155) were upregulated. The expression profile of mi RNAs was significantly associated with GBC prognosis and prediction, and forced over-expression/ inhibition of these mi RNAs was shown to affect tumor growth and development. Further, differential expression of mi RNAs in the blood samples of GBC patients suggest mi RNAs as promising noninvasive biomarker. Thus, mi RNAs represent potential candidate for GBC management, though many hurdles need to be overcome before mi RNAs therapy can be clinically applied to GBC prevention and treatment.
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.
