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.
【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.
【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.
Objective To study the relation between retinoblastoma (Rb) gene expression and biological characteristics of gallbladder carcinoma. Methods The expression of Rb protein in tissues of 41 cases of gallbladder carcinoma, 7 cases of gallbladder papilloma, and 14 cases of cholecystitis were detected by immunohistochemical staining of SP with polyclonal antibody. Results The rate of positive staining was 58.7% in gallbladder carcinoma which was significantly lower than that in cholecystitis and gallbladder papilloma (100%). There was a significant difference of Rb protein expression among the low, moderate and high differentiations and so was between S5, S4, S1, S2 and S3 stage (Ｐ＜0.05). Conclusion It sugests that expression or non-expression of Rb gene is closely related to the malignant potential invasiveness and prognosis of gallbladder carcinoma.
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.
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.
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 evaluate the expression of cyclin E and p27kip1 protein and their significance in gallbladder carcinoma. Methods SP immunohistochemistry was used to detect the expression of cyclin E and p27kip1 protein in 41 cases gallbladder carcinomas,15 cases chronic cholecystitis tissues. Results The positive rate of cyclin E in gallbladder carcinoma was 61.0%（25/41）,which was significantly higher than that in chronic cholecystitis (20.0%，3/15)，P＜0.05; The expression of cyclin E positively correlated with tumor TNM staging (r=0.314,P＜0.05). The positive rate of p27kip1 in gallbladder carcinoma was 53.7%(22/41),which was lower than that in chronic cholecystitis (100%). The positive rate of p27kip1 was decreased with the poor differentiation and progression of TNM staging. There was negative correlation between cyclin E and p27kip1 expression (r=-0.342,P＜0.05). Conclusion The high expression of cyclin E and the decreased expression of p27kip1 result in abnomal regulation of cell cycle,which may be associated with gallbladder carcinogenesis and progression.
ObjectiveTo study the relationship between mutation of the p53 gene, p21 gene and bacteria Lform in gallbladder carcinoma. MethodsForty cases of gallbladder carcinoma and 40 cases of chronic cholecystitis were studied by using Gram staining and immunohistochemistry (SP method) to detect the positive rate of Lforms antigen, p21 and p53 protein overpression. And the relationship between the expression of p21 and p53 in Lform infection positive group and that in Lform infection negative group was discussed. ResultsThere was no statistical difference between the Lform positive rate in patients with gallbladder carcinoma with Gram staining and immunohistochemistry (Pgt;0.05). The positive expression rate of p21 and p53 in gallbladder carcinoma was 62.5%(25/40) and 65.0%(26/40) respectively. The expression values of p21 and p53 in chronic cholecystitis was 2.5%(1/40) and 5.0%(2/40) respectively, which was significantly different from that of gallbladder carcinoma (P＜0.05). The expression of p21 and p53 was significantly higher in Lform infection positive group than in that with Lform infection negative group (P＜0.05). ConclusionBacteria Lform may be one of the direct factor leading to mutation of p53 and p21 during gallbladder oncogenesis.
【Abstract】Objective To investigate the expression of tumor growth tactor β1 (TGFβ1) and p27 in gallbladder carcinoma and their relation to the development of the carcinoma. Methods The expression of TGF-β1 and p27 in 36 cases of gallbladder carcinoma was detected by SP immunohistochemical staining. Twenty cases of chronic cholecystitis were collected as control. Results The positive rate of TGF-β1 （63.9%） was higher than that of the control （10.0%），P＜0.05， and the positive rate of p27 (47.2%) was lower than that of the control 100%(P＜0.05). The positive rate of TGF-β1 was significantly higher in metastasis or Nevin Ⅳ～Ⅴ stage cases than that of non-metastasis or Nevin Ⅰ～Ⅲ stage cases 33.3% (P＜0.05). The positive rate of p27 was statistically higher in moderate and highly differentiation (60.9%), nonmetastasis (75.0%) or Nevin’s Ⅰ～Ⅲ stage (75.0%) cases than those of poor differentiation (23.0%), metastasis (33.3%) and Nevin Ⅳ～Ⅴ stage (33.3%) cases (P＜0.05). The expression of p27 was negatively correlated with that of TGF-β1(r=-0.4473，P＜0.05). There was significant difference in survival time between patients with TGF-β1 positive and TGF-β1 negative（P＜0.05）. The difference was also found between patients with p27 positive and p27 negative. Conclusion The upregulation of TGF-β1 and downregulation of p27 in gallbladder carcinoma indicates the imbalance of TGF-β1/p27 system, which may play a role in the carcinogenesis and predict the malignant behaviors of the carcinoma.