Objective To explore the value of expression of carcinomaassociated antigens in early diagnosis and predicting prognosis in gallbladder carcinoma. MethodsThe expression of carcinoembryonic antigen (CEA), carbohydrate antigen (CA50), Ecadherin (ECD) and proliferating cell nuclear antigen (PCNA) in 10 cases of cholecystitis, 10 cases of gallbladder adenomas and 50 cases of gallbladder carcinomas were detected by immunohistochemistry. ResultsThe positive rate of CEA, CA50 and PCNA labeling index (LI) in gallbladder carcinomas were significantly higher than that of gallbladder adenomas and cholecystitis (P＜0.05 and P＜0.01). The positive rate of ECD in gallbladder carcinomas, especially with metastasis, was significantly lower than that of gallbladder adenomas and cholecystitis (P＜0.05). The 3year survival rate was significantly lower in gallbladder carcinomas with CEA and PCNA overexpression (P＜0.05), the 3year survival rate in patients with ECD positive tumors was higher than that of those with negative tumors (P＜0.05). Conclusion The detection of CEA, CA50 and PCNA is useful for early diagnosis of malignant change in gallbladder adenomas and gallbladder carcinomas. Therefore, the CEA, PCNA and ECD might be useful for predicting prognosis of gallbladder carcinomas.
【Abstract】Objective To design the hammerhead ribozyme gene according to the hTR sequence in the gallbladder cancer cell, and build it into the eukaryon expression vector pTriEx-4. Methods According to the hTR cDNA sequence, the authors designed the primers and take the hTR template area gene from the gallbladder cancer cells by RT-PCR.The hammerhead ribozyme gene was synthesize according to the result of sequencing, and combine them with eukaryon expressing vector. Identified the exactitude of recombine vector by digestion.Results The 68 bp sequence extracted from the cell through the RT-PCR had the same template sequence comparing with the hTR cDNA. The recombinant plasmid with the hammerhead ribozyme gene was correct by digestion identification. Conclusion The RT-PCR method can extract the gallbladder cancer cell’s hTR gene. We construct the eukaryon expression vector containing the hammerhead ribozyme gene successfully which is the foundation for gene therapy of gallbladder cancer.
The expression of p21, p53, bcl-2 oncoprotein was evaluated using immunohistochemistry in 40 patients with gallbladder carcinoma and 8 patients with gallbladder adenomous polyp. In the study, the positive rate of expression of p21, p53 and bcl-2 oncoprotein was 52.5%, 52.5% and 70.0% respectively in gallbladder carcinoma, while, in gallbladder polyp, they were 0%, 0% and 100% respectively. The positive rate of expression of p53 oncoprotein was significantly higher in poor-differentiated adenocarcinomas than in well-differentiated ones (Ｐ＜0.05). The converse was true for bcl-2 oncoprotein. The positive rate of expression of p21 and p53 oncoprotein was significantly higher in metastatic group than in non-metastatic one. These results suggest that the patients with the expression of p21, p53 might be of poor-prognosis.
Objective To summarize the development of gallbladder carcinoma related resistance genes and targeted therapy. Methods Domestic and international publications online involving resistance genes and targeted therapy of gallbladder carcinoma in recent years were collected and reviewed. Results Recent studies had shown that chemotherapy drug resistance of gallbladder carcinoma mainly involved lysosome protein transmembrane β4 （LAPTM4B） gene， NF-E2-related factor 2 （Nrf2） gene， and cancer stem cells （CSCs）. While the latest gene targets of treatment for gallbladder carcinoma mainly involved LAPTM4B， Nemo-like kinase （NLK）， tissue factor way inhibitor-2 （TFPI-2）， vascular endothelial growth factor-D （VEGF-D）， epidermal growth factor receptor （EGFR）， and melanoma differentiation-associated gene 7/interleukin 24 （mda-7/IL-24） gene. Conclusion The research involving resistance genes and targeted therapy of gallbladder carcinoma has make a certain progress， which broaden the concept of traditional treatment of gallbladder carcinoma.
Objective To explore the expression of tumor necrosis factor (TNF) mRNA, TNF and TNFR in the gallbladder mucosa which developed from hyperplasia, dysplasia to carcinoma, and to further discuss the relationship between TNF and pathogenesis of gallbladder carcinoma. Methods In situ hybridization and immunohistochemistry were used to determine TNF mRNA, TNF protein and TNFR protein expression in hyperplasia, dysplasia and carcinoma of gallbladder. Results ①No one of 20 cases of gallbladder hyperplasia was found to express TNF mRNA, while 4 of 20 (20%) cases of dysplasia and 18 of 20 (90%) cases of carcinoma were found to express TNF mRNA (P＜0.05). ②For the expression of TNF mRNA in mononuclear cells (MNC), positive staining was found in 15% of gallbladder hyperplasia, 85% of dysplasia and 90% of carcinoma, respectively (P＜0.05). The cell numbers of positive staining MNC were 4.85±1.50, 6.00±2.71 and 9.33±3.07, respectively (P＜0.05). ③In gallbladder carcinoma, the cell number of carcinoma and MNC with positive TNF mRNA expression was correlated with clinical stage (P＜0.05). The higher the clinical stage, the more the positive staining cell numbers. The positive staining cell numbers of carcinoma in stage Ⅰ-Ⅲ and Ⅳ-Ⅴ were 9.13±4.39 and 14.80±4.02, respectively (P＜0.01), and the positive staining cell numbers of MNC were 7.13±2.53 and 11.10±2.23, respectively (P＜0.05). ④The cell numbers of carcinoma and MNC with TNF mRNA expression increased with tumor size. In tumors with diameter over 2 cm and less than 2 cm, the positive staining cell numbers of carcinoma were 14.00±4.20 and 8.83±4.96, respectively (P＜0.05), and that of MNC were 10.50±2.54 and 7.00±2.83, respectively (P＜0.05). ⑤The region of TNF protein expression was similar to that of TNF mRNA, but TNF protein expression was more frequent and wider than that of TNF mRNA. ⑥The tumor necrosis factor receptor was expressed in tumoral vascular endothelial cells and MNC in all cases of carcinoma, but was negatively stained in mucosa epithelial cells and tumor cells of all cases. ⑦There was positive linear correlation in TNF mRNA between tumor cell and MNC (r=0.687, P＜0.01), same as that in TNF protein expression (r=0.742, P＜0.01); and there was positive linear correlation in tumor cell between TNF mRNA and TNF protein expression (r=0.847, P＜0.01), same as that in MNC (r=0.643, P＜0.01). Conclusion The TNF mRNA and TNF protein expression are increasing during the development of gallbladder mucosa epithelial from hyperplasia, dysplasia to carcinoma, and increasing with tumor stage. It suggests that TNF may contribute to carcinogenesis of gallbladder carcinoma induced by gallstone, and related to the progression of gallbladder carcinoma.
Objective To explore the effects of bile from patients with cholecystolithiasis on the growth of human gallbladder carcinoma cells GBC-SD and the potential correlation between cholecystolithiasis and gallbladder carcinoma. Methods Cholecystolithiasis bile (CB) and normal bile (NB) specimens were used for this study. The proliferative effects of bile were measured by methabenzthiazuron (MTT) assay and cell cycle and apoptosis were analyzed by flow cytometry. Results CB can significantly promote the proliferation of GBC-SD cells, GBC-SD proliferative index increased significantly after treated with 1% CB for 48 h （P＜0.05）.The Sphase fraction of CB 〔（49.26±8.07）%〕 increased remarkably (P＜0.05) compared with that of NB 〔（25.54±6.57）%〕, and the CB percentage of G0/G1 phase 〔（40.59±9.12）%〕 decreased remarkably (P＜0.05) compared with NB 〔(60.64±13.42）〕%. Conclusion CB can promote the proliferation of human gallbladder carcinoma GBC-SD cells.
【Abstract】ObjectiveTo explore the relationship between anomalous pancreaticobiliary ductal junction(APBDJ) and gallbladder carcinoma. MethodsThe current related literatures were reviewed.ResultsAPBDJ was associated with gallbladder carcinoma development. A proposed mechanism was free reflux of pancreatic juice into the gallbladder and molecular alterations of gallbladder epithelial cells.ConclusionAPBDJ is a high risk factor for gallbladder carcinoma. Prophylactic cholecystectomy is recommended for patients with APBDJ.
【Abstract】Objective To investigate the features of gallbladder carcinoma in two-phase spiral CT, and to analysis the values of two-phase spiral CT for the differential diagnosis between gallbladder carcinoma and chronic cholecystitis. Methods The two-phase spiral CT manifestations of 30 cases of gallbladder carcinoma, proved by surgery and pathology, and 30 cases of chronic cholecystitis were analyzed. Results According to the CT findings, the gallbladder carcinoma was categorized into 3 types: intraluminal mass of gallbladder in 6 out of 30 (20.0%）， thickening of the gallbladder wall in 11 (33.7%), and mass replacing the normal gallbladder in 13(43.4%). The most common enhancement patterns of the wall in gallbladder carcinoma were hyperattenuation during the arterial phase, while isoattenuation with the adjacent hepatic parenchyma during the venous phase; or hyperattenuation during both phases. The most common enhancement pattern of the wall in chronic cholecystitis was isoattenuation during both phases, with clear hypoattenuation linear shadow in the gallbladder fossa. Other ancillary features of gallbladder carcinomas included: infiltration of the adjacent parenchyma, local lymphadenopathy and intrahepatic metastasis. Conclusion Two-phase spiral CT scan can identify the features of the gallbladder carcinoma and is helpful for the differential diagnosis of these two different disease entities.
ObjectiveTo evaluate the diagnostic value of ultrasound for gallbladder carcinoma (GA), in order to improve the ability of early ultrasonic and clinical diagnosis of GA.
MethodsWe analyzed and compared the clinical data and ultrasonic results of 42 GA cases confirmed by surgery and pathology between January 2008 and December 2013, and summarized the classification, ultrasonographic features, and diagnosis of GA.
ResultsAmong the 42 cases, 25 were correctly diagnosed by ultrasound (59.5%), among which 9 were thick-wall type, 11 were protrusion type and 5 were solid type. Seventeen cases were misdiagnosed (40.5%). Pathological results showed 14 cases of highly-differentiated adenocarcinoma, 16 of moderately differentiaed adenocarcinoma, 9 of poorly-differentiated adenocarcinoma, 2 of squamous adenocarcinoma and 1 of neuroendocrine carcinoma.
ConclusionUltrasound is the preferred method for the diagnosis of GA because of its convenience, although the diagnostic accuracy is still not good and more efforts should be done.
Objective To study the relation between expressions of transforming growth factor β1 （TGF-β1）, transforming growth factor receptor type Ⅰ (TβRⅠ) and cell proliferation, cell cycle in gallbladder carcinomas, to disclose the mechanism of TGF-β1 and TβRⅠin the gallbladder carcinogenesis，and to evaluate their values in the prognosis of gallbladder carcinomas. Methods Thirty five gallbladder carcinomas 〔age （57.94± 4.61） years, 14 male cases and 21 female cases〕 comprised 32 adenocarcinomas, 2 adenosquamous carcinoma and 1 squamous cell carcinomas. Formalin fixed, paraffin embedded sections from gallbladder carcinomas were immunostained with TGF-β1, TβRⅠ, PCNA, cyclin E antibodies by immunochemical assays. Gallbladder adenoma and chronic cholecystitis were collected as non-malignant controls. Patients of gallbladder carcinomas were followed up. Results Positive immunostaining rate of TGF-β1 was 57.14% in gallbladder carcinomas, which was significantly higher than that in gallbladder adenomas and chronic cholecystitis (P＜0.01, respectively). Expression of TGF-β1 was associated with Nevin stage, lymph nodes and distant metastasis (P＜0.05, P＜0.01, respectively). Expression of TGF-β1 was positively correlated with expression of PCNA LI and cyclin E (r=0.523 2, P=0.001 3; r=0.406 5, P=0.015 4), and 34.29% of gallbladder carcinomas were immunostained positively for TβRⅠ. Expression of TβRⅠwas significantly lower in gallbladder carcinomas than that in gallbladder adenomas and cholecystitis (P＜0.05, respectively). It was significantly lower in gallbladder carcinomas patients with lymph nodes and distant metastases than in those without (P＜0.05). Expression of TβRⅠwas negatively correlated with PCNA LI (r=-0.402 4, P=0.016 6). Patients with negative expression of TGF-β1 and/or positive expression of TβRⅠ had significant longer survival rates than those with positive expression of TGF-β1 and/or negative expression of TβRⅠ(P＜0.01, P＜0.05, respectively). Expressions of TGF-β1 and TβRⅠ correlated with prognosis of gallbladder carcinomas closely. Conclusion TGF-β1 and TβRⅠ have close correlation with cell proliferation, cell cycle of gallbladder carcinomas and are important biological markers of carcinogenesis and progress of gallbladder carcinomas. The escape of growth inhibition of TGF-β1 due to low expression of TβRⅠand carcinogenesis of TGF-β1 may play an important role in gallbladder carcinogenesis. TGF-β1 and TβRⅠare valuable indices for judging the prognosis of gallbladder carcinoma.
