Esophageal carcinoma is one of the most virulent malignant diseases and a major cause of cancer-related deaths worldwide. Despite improvements in surgical techniques and perioperative management and surgery combined with chemotherapy and/or radiotherapy, the prognosis of esophageal squamous cell carcinoma (ESCC) at an advanced stage remains poor. ESCC shows a relatively high incidence of EGFR (50% - 70%), and the humanized monoclonal antibody (mAb) cetuximab against EGFR has been undergoing clinical development. However, all responding patients eventually developed acquired resistance to cetuximab. In the current study, we described a cetuximab-sensitive ESCC xeongraft model that developed resistance to cetuximab as a result of FGFR2 gene amplification and overexpression. Inhibition of FGFR2 signaling in this xenograft model restored its sensitivity to cetuximab. The antitumor effect may be induced by inhibition of AKT phosphorylation. These findings suggest that combination therapyincluding cetuximab and FGFR2 inhibition may be a promising strategy to treat ESCC.
A consistent positive association between cigarette smoking and the human esophageal cancer has been confirmed all over the world. However, details in the association need to be more focused on and be identified. Recently, aberrantly expressed microRNAs (miRNAs) have been shown to be promising biomarkers for understanding the tumorigenesis of a wide array of human cancers, including the esophageal cancer, and the deregulation on the epithelial to mesenchymal transition (EMT) by miRNAs is involved in the tumorigenesis. In present study, we were going to identify the role of nicotine-induced miR-21 in the EMT of esophageal cells. We found that there was an overexpression of miR-21 in esophageal specimens, having an association with cigarette smoking, and the upregulation of miR-21 was also induced by nicotine in esophageal carcinoma cell line, EC9706. Moreover, the upregulated miR-21 by nicotine promoted EMT transforming growth factor beta (TGF-?) dependently. Thus, the present study reveals a novel oncogenic role of nicotine in human esophageal cancer.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.