Esophageal Squamous Cell Carcinoma
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2021 ◽  
Vol 19 (1) ◽  
Xiang Li ◽  
Li Zhang ◽  
Xiamei Guo ◽  
Fei Xie ◽  
Cheng Shen ◽  

Abstract Background Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and have weak off-tumor targeting effects. Thus, they are among the most preferred carriers for mediating the targeted delivery of anti-tumor drugs. miR-375 was found to be significantly down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and its overexpression effectively inhibits the proliferation, migration, and invasion of ESCC cells. Moreover, epidermal growth factor receptor (EGFR) was overexpressed in ESCC cells, and accumulation of RNA nanoparticles in ESCC tumors was enhanced by EGFR-specific aptamer (EGFRapt) modification. Results Herein, a novel four-way junction RNA nanocarrier, 4WJ-EGFRapt-miR-375-PTX simultaneously loaded with miR-375, PTX and decorated with EGFRapt, was developed. In vitro analysis demonstrated that 4WJ-EGFRapt-miR-375-PTX possesses strong thermal and pH stabilities. EGFRapt decoration facilitated tumor cell endocytosis and promoted deep penetration into 3D-ESCC spheroids. Xenograft mouse model for ESCC confirmed that 4WJ-EGFRapt-miR-375-PTX was selectively distributed in tumor sites via EGFRapt-mediating active targeting and targeted co-delivery of miR-375 and PTX exhibited more effective therapeutic efficacy with low systemic toxicity. Conclusion This strategy may provide a practical approach for targeted therapy of ESCC. Graphical Abstract

2021 ◽  
Fangchao Zhao ◽  
Ren Niu ◽  
Yishuai Li ◽  
Zefang Dong ◽  
Xuebo Qin ◽  

Abstract Background: As the major type of esophageal cancer (ESCA), esophageal squamous cell carcinoma (ESCC) is also related to the highest malignant level and low survival rates across the world. Increasing people recognize long non-coding RNAs (lncRNAs) as significant mediators in regulating ferroptosis and iron-metabolism. Determining the prognostic value of ferroptosis and iron-metabolism related lncRNAs (FIRLs) in ESCC is thus critical. Methods: Pearson’s correlation analysis was carried out between ferroptosis and iron-metabolism-related genes (FIRGs) and all lncRNAs to derive the FIRLs. Based on weighted gene co-expression network exploration (WCGNA), least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis, a risk stratification system was established. According to Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis, and univariate and multivariate Cox regression analyses, the predictive ability and clinical relevance of the risk stratification system were evaluated. The validity of the established prognostic signature was further examined in TCGA (training set) and GEO (validation set) cohorts. A nomogram with enhanced precision for forecasting OS was set up on basis of the independent prognostic elements. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied for the identification of pathways in which FIRLs significantly enriched. we used cell culture, transfection, CCK-8, and qRT-PCR as in vitro assays. Results: An 3-FIRLs risk stratification system was developed by multivariate Cox regression analysis to divide patients into two risk groups. Patients in the high-risk group had worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed the risk stratification system was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The area under time-dependent ROC curve (AUC) reached 0.853 at 1 year, 0.802 at 2 years, 0.740 at 5 years in the training cohort and 0.712 at 1 year, 0.822 at 2 years, 0.883 at 5 years in the validation cohort. Functional enrichment analysis predicted potential associations of 49 possible upstream regulated FIRGs with ferroptosis and iron-metabolism processes and oncological signatures. Analysis of the immune cell infiltration landscape showed that ESCC in the high-risk group tended be immunologically “cold”. In vitro experiments suggested that LINC01068 promoted ESCC cell proliferation. Conclusion: The risk stratification system based on FIRLs could serve as a reliable tool for forecasting the survival of patients with ESCC.

2021 ◽  
Vol 19 (1) ◽  
Peng Yang ◽  
Xiao Zhou ◽  
Xuefeng Yang ◽  
Yuefeng Wang ◽  
Tao Sun ◽  

Abstract Background Camrelizumab (a PD-1 inhibitor) has been used as a potential therapy in unresectable advanced esophageal squamous cell carcinoma (ESCC) along with adjuvant treatment in locally advanced ESCC, exhibiting an acceptable efficacy and safety profile. This pilot study was designed to further investigate the clinical value and tolerance of neoadjuvant camrelizumab plus chemotherapy in locally advanced ESCC. Methods A total of 16 patients with locally advanced ESCC were recruited. Patients received 2 cycles of neoadjuvant therapy including 2 doses of camrelizumab concurrent with 2 cycles of paclitaxel plus carboplatin followed by surgery 4 weeks afterward. Then, the treatment response after neoadjuvant therapy, R0 resection rate, tumor regression grade (TRG), and pathological complete remission (pCR) rate were measured. Besides, adverse events were documented. At last, progression-free survival (PFS) and overall survival (OS) were assessed. Results Generally, objective remission rate (ORR) was 81.3% whereas disease control rate (DCR) was 100% after neoadjuvant therapy. Concerning TRG grade, 31.3, 37.5, 18.8, and 12.5% patients reached TRG0, TRG1, TRG2, and TRG3, respectively. Then, pCR rate and R0 resection rate were 31.3 and 93.8%, respectively. Besides, mean PFS and OS were 18.3 months (95%CI: (16.2–20.5) months) and 19.2 months (95%CI: (17.7–20.7) months), respectively, with a 1-year PFS of 83% and OS of 90.9%. Adverse events included white blood cell decrease (37.5%), neutrophil decrease (31.3%), reactive cutaneous capillary endothelial proliferation (37.5%), and nausea or vomiting (25.0%), which were relatively mild and manageable. Conclusion Neoadjuvant camrelizumab plus chemotherapy exhibits good efficacy and acceptable tolerance in patients with locally advanced ESCC.

2021 ◽  
Vol 11 ◽  
Tian Zeng ◽  
Lei Zhang ◽  
Can Chen ◽  
Xiang Zhao ◽  
Xiaoqing Liu ◽  

Microsatellite instability-high (MSI-H) is widely believed to be a biomarker for immune checkpoint inhibitors (ICIs) such as pembrolizumab in solid tumors. However, due to the low prevalence of MSI-H in most cancers, it tends to be insufficient to identify whether patients should receive ICIs according to this biomarker alone. Here, we report a Chinese esophageal squamous cell carcinoma (ESCC) patient with unusual divergent MSI status between the primary lesion (MSS) and metastatic lesion (MSI-H) which developed after platinum-based therapy and radiotherapy. Both his primary and metastatic tumors responded well to pembrolizumab-containing therapies or pembrolizumab monotherapy and maintained a complete response for over 24 months. Whole-exome sequencing and multiplex immunohistochemistry were used to examine his tissue specimens. Notably, there were multiple high-frequency mutations of DDR (DNA damage repair) genes shared in the primary lesion and metastatic lesion, especially in the latter. Besides, we observed considerable degrees of infiltrating CD3+/CD8+ lymphocytes in both of his primary tumor and metastatic tumor without obvious difference, suggesting that the conversion of microsatellite status had little effect on the infiltration of lymphocytes. Collectively, given the predictive role of DDR alterations for ICIs in other malignancies, the alterations of DDR genes might also be promising biomarkers in ESCC individuals receiving ICIs.

2022 ◽  
Vol 12 (2) ◽  
pp. 293-298
Wenxiu Qian ◽  
Guomin Li

Angiogenesis is a prerequisite for tumor development and metastasis. Emerging evidence shows that tumor-derived extracellular vesicles (EVs) are an important component of tumor microenvironment, which participate in the communication between normal cells and tumor cells. In this study, we aimed to investigate the role of EVs derived from esophageal squamous cell carcinoma (ESCC) on tumor angiogenesis. We found that ESCC cell-derived EVs promoted the proliferation, migration, and tubule formation of human umbilical vein endothelial cells in vitro, and enhanced angiogenesis and tumor growth in vivo. Our results suggest that ESCC cell-derived EVs could promote angio-genesis and tumor growth, which also indicated the application of EVs as a valuable therapeutic strategy of ESCC.

2021 ◽  
Vol 11 ◽  
Chuangzhen Chen ◽  
Jianzhou Chen ◽  
Ting Luo ◽  
Siyan Wang ◽  
Hong Guo ◽  

PurposeWe aimed to evaluate the long-term outcomes of concurrent chemoradiotherapy (CCRT) with a simultaneous integrated boost (SIB) of radiotherapy for esophageal squamous cell carcinoma (ESCC).Methods and MaterialsEighty-seven patients with primary ESCC enrolled in this phase II trial. The majority (92.0%) had locoregionally advanced disease. They underwent definitive chemoradiotherapy. The radiotherapy doses were 66 Gy for the gross tumor and 54 Gy for the subclinical disease. Doses were simultaneously administered in 30 fractions over 6 weeks. The patients also underwent concurrent and adjuvant chemotherapy, which comprised cisplatin and fluorouracil. The study end points were acute and late toxicities, first site of failure, locoregional tumor control, and overall survival rates.ResultsThe median follow-up time was 65.7 (range, 2.2-97.5) months for all patients and 81.5 (range, 19.4-97.5) months for those alive. There were 17 cases (19.5%) of severe late toxicities, including four cases (4.6%) of grade 5 and seven (8.0%) of grade 3 esophageal ulceration, four (4.6%) of grade 3 esophageal stricture, and two (2.3%) of grade 3 radiation-induced pneumonia. Twenty-three (26.4%) patients had locoregional disease progression. Most (86.7%) locally progressive lesions were within the dose-escalation region in the initial radiation plan, while majority of the recurrent lymph nodes were found out-of-field (83.3%) and in the supraclavicular region (75.0%). The 1-, 2-, 3-, and 5-year locoregional tumor control and overall survival rates were 79.2%, 72.4%, 72.4%, 70.8%, and 82.8%, 66.6%, 61.9%, 58.4%, respectively. Incomplete tumor response, which was assessed immediately after CCRT was an independent risk predictor of disease progression and death in ESCC patients.ConclusionsCCRT with SIB was well tolerated in ESCC patients during treatment and long-term follow-up. Moreover, patients who underwent CCRT with SIB exhibited improved local tumor control and had better survival outcomes compared to historical data of those who had standard-dose radiotherapy.

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