Guangdong Esophageal Cancer Institute

Guangzhou, China

Guangdong Esophageal Cancer Institute

Guangzhou, China
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Deng H.,South China Normal University | Liu Q.,Sun Yat Sen University | Liu Q.,Guangdong Esophageal Cancer Institute | Liu Q.,State Key Laboratory of Oncology in South China | And 8 more authors.
Biosensors and Bioelectronics | Year: 2017

MicroRNAs (miRNAs) have been proved to be potential biomarkers in early cancer diagnosis. It is of great significance for rapid and sensitive detection of miRNAs, particularly with point-of-care (POC) diagnosis. Herein, it is the first time to construct quantum dots (QDs)-labeled strip biosensor based on target-recycled nonenzymatic amplification strategy for miRNA detection. In the system, QDs were served as bright, photostable signal labels, which endow this biosensor with good detection efficiency. Moreover, a target-recycled amplification strategy relies on sequence-specific hairpins strand displacement process without the assistance of enzymes, was introduced to further improve the sensitivity. Meanwhile eliminating the requirement of environment-susceptible enzyme protein makes it easy to preserve and enhances the stability and reproducibility of this sensor. Benefiting from these outstanding characteristics, this platform exhibited a good detection sensitivity range from 2 fmol to 200 fmol with a limit of 200 amol, using only 20 μL of sample within 80 min. The assay was also 10-fold more sensitive than that with a conventional colloidal gold-based test strip for miRNA detection. Additionally, the analysis of miRNA in various tumor cell extracts was in accordance with the performance of quantitative realtime polymerase chain reaction (qRT-PCR). Clinical tumor samples were also tested, and 16 of 20 samples gave out positive signals, which demonstrated the practical application capacity of the biosensor. Therefore, the proposed biosensor holds great promise for potential POC applications and early cancer diagnosis. © 2016 Elsevier B.V.

Hou X.,Sun Yat Sen University | Hou X.,State Key Laboratory of Oncology in South China | Wei J.-C.,Linzhou Esophageal Cancer Hospital | Fu J.-H.,State Key Laboratory of Oncology in South China | And 10 more authors.
Annals of Surgical Oncology | Year: 2015

Background: The correlation between vascular endothelial growth factor (VEGF) and prognosis for patients with esophageal squamous cell carcinoma (ESCC) is controversial. This study investigated the correlation of VEGF expression with distant metastases and prognosis in resectable ESCC to improve the identification of patients with increased risk of postoperative metastases. Methods: Data from two centers were used to establish a training cohort (n = 319) and a validation cohort (n = 164). Tissue microarrays were generated for immunohistochemical evaluation. The correlations among VEGF expression, clinicopathologic variables, and prognosis were analyzed. The outcomes generated from the training cohort then were tested using the validation cohort. Multivariate analyses were used to test the independent factors that had an impact on postoperative distant metastases, overall survival (OS), and distant metastasis-free survival (DMFS). Results: Tumor stages, tumor cell grade, and VEGF expression were prognostic factors independent of ESCC outcome. The data indicated that high levels of VEGF expression were correlated with a high risk of postoperative distant metastases (p = 0.013) in the training cohort. This result was confirmed by the validation cohort (p < 0.01) and logistic regression analyses. A high level of VEGF expression also was correlated with poor DMFS (p = 0.011) and OS (p = 0.033) in the training cohort, which also was confirmed by the validation cohort and Cox regression analyses. Conclusions: Expression of VEGF is a predictor of distant metastasis, OS, and DMFS in resectable ESCC patients. Using a combination of VEGF expression, tumor stages, and tumor cell grade, identification of patients with increased risk of postoperative metastases may become possible. © 2015, Society of Surgical Oncology.

Yang H.,Sun Yat Sen University | Yang H.,Guangdong Esophageal Cancer Institute | Wang J.,Sun Yat Sen University | Huang Q.,Sun Yat Sen University | And 10 more authors.
Diseases of the Esophagus | Year: 2016

The rate of vocal cord palsy following resection for esophageal carcinoma has increased due to lymphadenectomy around the recurrent laryngeal nerves (RLN). The aim of this pilot study was to assess the ability of intraoperative ultrasonography to detect thoracic RLN node metastases in patients with esophageal cancer. Intraoperative ultrasonography was performed during esophagectomy to assess whether RLN lymph nodes were metastatic in 10 patients with esophageal squamous cell cancer. All patients underwent RLN lymphadenectomy, and the nodes were assessed for metastasis. Three patients had pathological RLN lymph node metastases, of which one had right RLN node metastasis, and three had left RLN node metastases. For detecting right RLN lymph node metastasis, the sensitivity, specificity, and positive and negative predictive values of intraoperative ultrasonography were 100%, 33.3%, 14.3%, and 100%, respectively. For the detection of left RLN lymph node, these values were 100%, 85.7%, 75%, and 100%, respectively. This study suggests that intraoperative ultrasonography is feasible and safe to detect RLN lymph node metastases for patients with esophageal cancer. Further study will be performed to evaluate the validity and utility of this diagnostic technique. © 2016 International Society for Diseases of the Esophagus.

Chen J.,Sun Yat Sen University | Chen J.,Guangdong Esophageal Cancer Institute | Yang H.,Sun Yat Sen University | Yang H.,Guangdong Esophageal Cancer Institute | And 15 more authors.
Oncotarget | Year: 2015

Recently, we found that NHE9 mRNA was upregulated in chemoradiotherapy (CRT)-resistant esophageal squamous cell carcinoma (ESCC); however, the underlying mechanisms were unclear. Here, we aimed to clarify the functional contribution of NHE9 to CRT resistance, understand the molecular basis of NHE9-dependent resistance in ESCC, and identify potential therapeutic targets. Our results showed that NHE9 prevented CRT-induced apoptosis. Importantly, we found that RACK1 is a novel binding partner of NHE9 and that NHE9-dependent induction of CRT resistance requires the activation of RACK1-associated Src/Akt/β-catenin signaling. Moreover, upregulated Bcl-2 protein was also observed in cells exhibiting NHE9-induced CRT resistance. A higher NHE9 level was associated with a poor response to CRT and less decrease in T and N stage in ESCC patients. Furthermore, combining either Dasatinib or ABT-737 with CRT significantly reduced tumor volume, and the response to CRT was restored when these inhibitors were used together with CRT in a xenograft nude mouse model with NHE9 overexpression. Taken together, our findings demonstrate that NHE9 can be an effective predictor of CRT response and may be useful in the development of targeted therapies for CRT-resistant ESCC.

Chen Z.,Sun Yat Sen University | Chen Z.,Guangdong Esophageal Cancer Institute | Chen Y.,Sun Yat Sen University | Xu M.,Sun Yat Sen University | And 10 more authors.
Molecular Cancer Therapeutics | Year: 2016

The overexpression of ATP-binding cassette (ABC) transporters has been proved to be a major trigger for multidrug resistance (MDR) in certain types of cancer. In our study, we investigated whether osimertinib (AZD9291), a third-generation irreversible tyrosine kinase inhibitor of both activating EGFR mutations and resistance-associated T790M point mutation, could reverse MDR induced by ABCB1 and ABCG2 in vitro, in vivo, and ex vivo. Our results showed that osimertinib significantly increased the sensitivity of ABCB1- and ABCG2-overexpressing cells to their substrate chemotherapeutic agents in vitro and in the model of ABCB1-overexpressing KBv200 cell xenograft in nude mice. Mechanistically, osimertinib increased the intracellular accumulations of doxorubicin (DOX) and Rhodamine 123 (Rho 123) by inhibiting the efflux function of the transporters in ABCB1- or ABCG2-overexpressing cells but not in their parental sensitive cells. Furthermore, osimertinib stimulated the ATPase activity of both ABCB1 and ABCG2 and competed with the [125 I] iodoarylazidoprazosin photolabeling bound to ABCB1 or ABCG2, but did not alter the localization and expression of ABCB1 or ABCG2 in mRNA and protein levels nor the phosphorylations of EGFR, AKT, and ERK. Importantly, osimertinib also enhanced the cytotoxicity of DOX and intracellular accumulation of Rho 123 in ABCB1-overexpressing primary leukemia cells. Overall, these findings suggest osimertinib reverses ABCB1- and ABCG2-mediated MDR via inhibiting ABCB1 and ABCG2 from pumping out chemotherapeutic agents and provide possibility for cancer combinational therapy with osimertinib in the clinic. ©2016 American Association for Cancer Research.

Wang X.-P.,Sun Yat Sen University | Li X.-H.,Sun Yat Sen University | Zhang L.,Sun Yat Sen University | Zhang L.,Guangdong Esophageal Cancer Institute | And 6 more authors.
BMC Cancer | Year: 2016

Background: Noninvasive prognostic tools for esophageal squamous cell carcinoma (ESCC) are urgently needed. Serum lipids and lipoproteins are used for the prognosis of certain diseases; however, the prognostic value of serum apolipoprotein A-I (ApoA-I) in ESCC has not been described. Methods: Pre-treatment serum lipids and lipoprotein concentrations (including ApoA-I, Apo-B, HDL-C, LDL-C, TC and TG) were analyzed retrospectively and compared between 210 patients with ESCC and 219 healthy controls. The prognostic significance of serum lipids and lipoproteins was determined by univariate and multivariate Cox hazard models in ESCC. Results: Clinical characteristics (age, sex, pT status, pN status, pM status, pTNM status, histological differentiation or alcohol index) had no influence on baseline ApoA-I level. Serum ApoA-I, HDL-C, LDL-C, and TC levels were significantly lower and Apo-B was significantly higher in ESCC patients than in normal controls. On univariate analysis, ApoA-I, alcohol index, pT status, pN status and pTNM status were associated with significantly poor survival, and ApoA-I (p = 0.039), alcohol index (p = 0.037) and pTNM status (p = 0.000) were identified as prognostic factors associated with shorter survival in the multivariate analysis. Conclusions: Overall survival was shorter in ESCC patients with decreased pre-treatment ApoA-I levels. Our findings suggest that serum ApoA-I level should be evaluated as a predictor of survival in patients with ESCC. © 2016 Wang et al.

Wen J.,Collaborative Innovation Center for Cancer Medicine | Wen J.,Guangdong Esophageal Cancer Institute | Yang H.,Collaborative Innovation Center for Cancer Medicine | Yang H.,Guangdong Esophageal Cancer Institute | And 25 more authors.
Annals of Oncology | Year: 2014

Background: Neoadjuvant chemoradiotherapy (neo-CRT) followed by surgery has been shown to improve esophageal squamous cell carcinoma (ESCC) patients' survival compared with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method can currently predict CRT response. In this study, we aim to identify mRNA markers useful for ESCC CRT-response prediction. Patients and methods: Gene expression analyses were carried out on pretreated cancer biopsies from 28 ESCCs who received neo-CRT and surgery. Surgical specimens were assessed for pathological response to CRT. The differentially expressed genes identified by expression profiling were validated by real-time quantitative polymerase chain reaction (qPCR), and a classifying model was built from qPCR data using Fisher's linear discriminant analysis. The predictive power of this model was further assessed in a second set of 32 ESCCs. Results: The profiling of the 28 ESCCs identified 10 differentially expressed genes with more than a twofold change between patients with pathological complete response (pCR) and less than pCR (

Yang H.,Sun Yat Sen University | Yang H.,Guangdong Esophageal Cancer Institute | Li X.-d.,Sun Yat Sen University | Li X.-d.,Guangdong Esophageal Cancer Institute | And 10 more authors.
Oncotarget | Year: 2015

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies of the digestive tract in East Asian countries. Multimodal therapies, including adjuvant chemotherapy and neo-adjuvant chemotherapy, have become more often used for patients with advanced ESCC. However, the chemotherapy effect is often limited by patients' drug resistance. This study demonstrated that EIF5A2 (eukaryotic translation initiation factor 5A2) overexpression induced stemness and chemoresistance in ESCC cells. We showed that EIF5A2 overexpression in ESCC cells resulted in increased chemoresistance to 5-fluorouracil (5-FU), docetaxel and taxol. In contrast, shRNAs suppressing eIF5A2 increased tumor sensitivity to these chemotherapeutic drugs. In addition, EIF5A2 overexpression was correlated with a poorer overall survival in patients with ESCC who underwent taxane-based chemotherapy after esophagectomy (P > 0.05). Based on these results, we suggest that EIF5A2 could be a predictive biomarker for selecting appropriate chemo-treatment for ESCC patients and EIF5A2 inhibitors might be considered as combination therapy to enhance chemosensitivity in patients with ESCC.

PubMed | Indiana University, Guangdong Esophageal Cancer Institute and Sun Yat Sen University
Type: | Journal: Molecular cancer research : MCR | Year: 2017

14-3-3sigma has been implicated in the development of chemo and radiation resistance and in poor prognosis of multiple human cancers. While it has been postulated that 14-3-3sigma contributes to these resistances via inhibiting apoptosis and arresting cells in G2/M phase of the cell cycle, the molecular basis of this regulation is currently unknown. In this study, we tested the hypothesis that 14-3-3sigma causes resistance to DNA-damaging treatments by enhancing DNA repair in cells arrested in G2/M phase following DNA-damaging treatments. We showed that 14-3-3sigma contributed to ionizing radiation (IR) resistance by arresting cancer cells in G2/M phase following IR and by increasing non-homologous end joining (NHEJ) repair of the IR-induced DNA double strand breaks (DSBs). The increased NHEJ repair activity was due to 14-3-3sigma-mediated up-regulation of Poly(ADP-ribose) polymerase 1 (PARP1) expression that promoted the recruitment of DNA-PKcs to the DNA damage sites for repair of DSBs. On the other hand, the increased G2/M arrest following IR was due to 14-3-3sigma-induced Chk2 expression.These findings reveal an important molecular basis of 14-3-3sigma function in cancer cell resistance to chemo/radiation therapy and in poor prognosis of human cancers.

PubMed | Guangdong Esophageal Cancer Institute and Sun Yat Sen University
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

The migration and invasion inhibitory protein (MIIP) was shown to function as a tumor suppressor gene in gliomas by inhibiting tumor cell growth, migration, and invasion. However, its role and clinical significance in esophageal squamous cell carcinoma (ESCC) have not been elucidated. We investigated the correlation of MIIP expression and clinical outcome in a group of surgically resected ESCCs. Tissue microarrays constructed of 253 surgically resected ESCC primary tumors and paired paracancerous normal esophageal epithelia were used for MIIP evaluation by immunohistochemistry. The clinical and prognostic significance of MIIP expression was analyzed statistically. The expression of MIIP expression in cancer tissues was increased significantly in comparison with the paired paracancerous normal epithelia (P<0.001). And, MIIP expression was associated with ESCC cells differentiation (P<0.001). By Kaplan-Meier analysis, patients with low MIIP expression exhibited significantly improved overall survival (OS, P=0.039) and a tendency of improved disease-free survival (DFS, P=0.086) than those with high MIIP expression. In addition, MIIP expression could distinguish OS or DFS of patients with tumors in stage T3-4 (P=0.020, 0.028), N0 (P=0.008, 0.032), and stage II (P=0.004, 0.019), as well as at lower thoracic esophagus (P=0.024, 0.090). Multivariate analysis showed that MIIP expression was an independent prognostic factor in ESCC OS and DFS. In conclusion, MIIP expressed higher in ESCCs than in paracancerous normal esophageal epithelia and was a positive, independent prognostic factor in resected ESCCs.

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