ABSTRACT
Glioblastoma (GBM) is the most common primary brain tumor, which is prone to recurrence and metastasis with poor prognosis. In recent years, immunotherapy has prolonged the survival of patients with GBM, providing a new option for the treatment of GBM. Target selection is very important for immunotherapy. Epidermal growth factor receptor variant III (EGFRvIII) is highly expressed on the surface of GBM cells in some patients, and EGFRvIII was not expressed in normal tissues. EGFRvIII are pivotal for the occurrence and progression of GBM, various targeted therapy including immunotherapy is promising to improve the efficacy of GBM. Currently, there are various approaches to target EGFRvIII, including humanized monoclonal antibodies, adoptive cell therapies and therapeutic vaccines. In this review, we focus on the preclinical and clinical findings of targeting EGFRvIII for GBM.
ABSTRACT
@#[Abstract] EGFRvIII (epidermal growth factor receptor variant Ⅲ) is the most common mutant of epidermal growth factor receptor, which expresses in over 30% glioblastoma multiforme (GBM). EGFRvIII results from deletion of exon 2-7, leading to its constitutive activation, which is closely related to tumorigenesis, development and poor prognosis of GBM. The unique glycine site on EGFRvIII provides ideal molecular target for immunotherapy, which possess great potential value of killing GBM cell, inhibiting progress and invasion. Encouraging progress has been achieved in peptide/DC vaccine, therapeutic antibody, small molecular inhibitor and adoptive immunotherapy experimentally and clinically. The characteristics of EGFRvIII and the development in its oriented immunotherapy were summarized in this review.
ABSTRACT
Background and purpose: It has been reported that epidermal growth factor receptor (EGFR) and epidermal growth factor receptor variant Ⅲ (EGFRv Ⅲ) play important roles in the progression of various cancers. This research was to detect the expression and relation of EGFR and epidermal growth factor receptor variant Ⅲ (EGFRv Ⅲ) to human esophageal carcinoma. Methods: In 66 human esophageal carcinoma tissues, the expression of EGFR and EGFRv Ⅲ were detected by imrnunohistochemistry and western-blot. The expression of EGFR and EGFRv Ⅲ along with the patients' clinicopathologic factors was retrospectively analyzed. Correlation analysis between EGFRv Ⅲ and EGFR was analyzed by Pearson correlation coefficient. Results: The average gray scale values of EGFR in esophageal carcinoma and normal tissues by immunohistochemistry were 25.4±3.2 and 5.0±3.5, which showed a significant difference (t=5.574, P=0.000). And the average gray scale values of EGFRv Ⅲ in esophageal carcinoma and normal tissues were 22.5±4.2 and 5.5±3.0, which also showed a significant difference (t=6.701,P=0.000). The average gray scale values of EGFR in esophageal carcinoma and normal tissues respectively by western-blot were 1.37±0.41 and 0.21±0.09, which showed a significant difference (t=10.704, P=0.000) And the average gray scale values of EGFRv Ⅲ respectively were 0.828±0.15 and 0.083±0.049, which had a significant difference (t=9.362, P=0.000). Significant differences were observed in TNM-stage, lymphatic metastasis and tumor classification in both the expression of EGFR (P<0.05) and EGFRv Ⅲ (P<0.05), and but there were no obvious differences in gender, age, minor size, growth pattern in both the expression of EGFR (P<0.05) and EGFRvⅢ (P<0.05). Correlation analysis showed that there was strong association of the expression between EGFR and EGFRv Ⅲ both detected by immunohistochemistry (r=0.701,P<0.0001) and western-blot respectively(r=0.556, P=0.031). Conclusion: Our data suggests that EGFRvⅢ is over-expressed in human esophageal carcinoma. Combination of EGFR and EGFRvⅢ could be useful markers for tumorgenesis and differentiation of human esophageal carcinoma.
ABSTRACT
Objective To detect expression of epidermal growth factor receptor variant Ⅲ (EGFRvⅢ) in human suprarenal epithelioma to explore its relation with the genesis and development of suprarenal epithelioma.Methods Immunohistochemistry and pathologic image analysis were used to semiquantitatively detect the expression of EGFRvⅢ protein in eighty human suprarenal epithelioma tissues and twenty-four normal renal tissues.Results Positive expression rate of EGFRvⅢ was 46% in human suprarenal epithelioma tissues and 8% in normal renal tissues.Their average gray scale values were 148.49?13.05 and 155.65?14.86,respectively,which showed a significant difference (t=2.13,P=0.04).There was no obvious difference between males and females (149.01?13.70 and 147.40?11.76,t=0.54,P=0.59).No significant association was observed between EGFRvⅢ expression and age (r=0.01,P=0.92).Conclusion Many human suprarenal epithelioma tissues express EGFRvⅢ.EGFRvⅢ may play certain role in the genesis and development of human suprarenal epithelioma.