scholarly journals Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

2014 ◽  
pp. 1083 ◽  
Author(s):  
Dongxi Xiang ◽  
Sarah Shigdar ◽  
Wenrong Yang ◽  
Wei Duan ◽  
Qiong Li ◽  
...  
2016 ◽  
Vol 23 (3) ◽  
pp. 171 ◽  
Author(s):  
A. Wang ◽  
R. Ramjeesingh ◽  
C.H. Chen ◽  
D. Hurlbut ◽  
N. Hammad ◽  
...  

Background Epithelial cell adhesion molecule (EpCAM) is a multifunctional transmembrane glycoprotein expressed on both normal epithelium and epithelial neoplasms such as gastric, breast, and renal carcinomas. Recent studies have proposed that the proteolytic cleavage of the intracellular domain of EpCAM (EpCAM-ICD) can trigger signalling cascades leading to aggressive tumour behavior. The expression profile of EpCAM-ICD has not been elucidated for primary colorectal carcinoma. In the present study, we examined EpCAM-ICD immunohistochemical staining in a large cohort of patients with primary colorectal adenocarcinoma and assessed its performance as a potential prognostic marker.MethodsImmunohistochemical staining for EpCAM-ICD was assessed on tissue microarrays consisting of 137 primary colorectal adenocarcinoma samples. Intensity of staining for each core was scored by 3 independent pathologists. The membranous EpCAM-ICD staining score was calculated as a weighted average from 3 core samples per tumour. Univariate analysis of the average scores and clinical outcome measures was performed.Results The level of membranous EpCAM-ICD staining was positively associated with well-differentiated tumours (p = 0.01); low preoperative carcinoembryonic antigen (p = 0.001); and several measures of survival, including 2-year (p = 0.02) and 5-year survival (p = 0.05), and length of time post-diagnosis (p = 0.03). A number of other variables — including stage, grade, and lymph node status—showed correlations with EpCAM staining and markers of poor outcome, but did not reach statistical significance.ConclusionsLow membranous EpCAM-ICD staining might be a useful marker to identify tumours with aggressive clinical behavior and potential poor prognosis and might help to select candidates who could potentially benefit from treatment targeting EpCAM.


Author(s):  
Fatemeh Sadat Javadian ◽  
Majid Basafa ◽  
Aidin Behravan ◽  
Atieh Hashemi

Abstract Background Overexpression of the EpCAM (epithelial cell adhesion molecule) in malignancies makes it an attractive target for passive immunotherapy in a wide range of carcinomas. In comparison with full-length antibodies, due to the small size, the scFvs (single-chain variable fragments) are more suitable for recombinant expression in E. coli (Escherichia coli). However, the proteins expressed in large amounts in E. coli tend to form inclusion bodies that need to be refolded which may result in poor recovery of bioactive proteins. Various engineered strains were shown to be able to alleviate the insolubility problem. Here, we studied the impact of four E. coli strains on the soluble level of anti-EpEX-scFv (anti-EpCAM extracellular domain-scFv) protein. Results Although results showed that the amount of soluble anti-EpEX-scFv obtained in BL21TM (DE3) (114.22 ± 3.47 mg/L) was significantly higher to those produced in the same condition in E. coli RosettaTM (DE3) (71.39 ± 0.31 mg/L), and OrigamiTM T7 (58.99 ± 0.44 mg/L) strains, it was not significantly different from that produced by E. coli SHuffleTM T7 (108.87 ± 2.71 mg/L). Furthermore, the highest volumetric productivity of protein reached 318.29 ± 26.38 mg/L in BL21TM (DE3). Conclusions Although BL21TM (DE3) can be a suitable strain for high-level production of anti-EpEX-scFv protein, due to higher solubility yield (about 55%), E. coli SHuffleTM T7 seems to be better candidate for soluble production of scfv compared to BL21TM (DE3) (solubility yield of about 30%).


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