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1.  Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer 
The Indian Journal of Medical Research  2016;143(Suppl 1):S82-S90.
Background & objectives:
Loss of function of adenomatous polyposis coli (APC) has been reported in cancer. The two promoters of APC, 1A and 1B also have roles in cancer. But, the epigenetic role of APC promoters is not yet clear in gallbladder cancer (GBC) and gallstone diseases (GSD). We undertook this study to determine the epigenetic role of APC in GBC and GSD.
Methods:
Methylation-specific (MS)-PCR was used to analyze the methylation of APC gene. The expression of APC gene was studied by semi-quantitative PCR, real-time PCR and immunohistochemistry (IHC) in GBC, GSD and adjacent normal tissues.
Results:
Of the two promoters, APC 1A promoter was found methylated in 96 per cent GBC (P=0.0155) and 80 per cent GSD (P=0.015). Exon 1 was downregulated in grade II (P=0.002) and grade III (P=0.0001) of GBC, while exon 2 was normally expressed. Scoring analysis of IHC revealed 0 or negativity in 34.48 per cent (P=0.057) and 1+ in 24.14 per cent (P=0.005) GBC cases suggesting loss of APC expression.
Interpretation & conclusions:
The present findings indicate epigenetic silencing of APC in advanced GBC. The methylation pattern, followed by expression analysis of APC may be suggested for diagnostic, prognostic and therapeutic purposes in GBC in future.
doi:10.4103/0971-5916.191792
PMCID: PMC5080933  PMID: 27748282
Adenomatous polyposis coli; epigenetics; gallbladder cancer; gallstone disease; tissue microarray
3.  Quantitative Assessment of Expression of Lactate Dehydrogenase and its Isoforms 3 and 4 may Serve as Useful Indicators of Progression of Gallbladder Cancer: A Pilot Study 
We have studied the expression of lactate dehydrogenase and its isoforms in gall bladder cancer, cholelithiasis and chronic cholecystitis. Quantitative and qualitative assays of lactate dehydrogenase and its various isoforms were carried out in the blood sera of patients and healthy controls along with parallel estimation of various liver function test enzymes. Statistical analysis was done using the software Graph Pad Prism. Significantly high expression of lactate dehydrogenase along with alkaline phosphatase and total bilirubin (P ≤ 0.05) was observed in all the three clinical conditions as compared to controls. LDH showed an increasing trend from stage I to stage IV of GBC indicating a significant positive association with the disease progression. The levels of LDH 3 and 4 isoforms appeared significantly more elevated in GBC than cholelithiasis or chronic cholecystitis. We suggest that a careful estimation of total LDH and its isoforms 3 and 4 alone or along with alkaline phosphatase and total bilirubin during different clinical stages, like chronic cholecystitis, cholelithiasis and GBC, may prove to be a potentially useful biomarker in the prognostic management of gall bladder diseases, specifically GBC.
doi:10.1007/s12291-011-0117-3
PMCID: PMC3107415  PMID: 22468041
Gallbladder cancer; Lactate dehydrogenase; Cholelithiasis; Chronic cholecystitis

Results 1-3 (3)