• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.7
• /
• pp.3233-3238
• /
• 2012

Esophageal carcinoma (EC) is one of the most aggressive cancers with a poor prognosis. Understanding the molecular mechanisms underlying esophageal cancer progression is a high priority for improved EC diagnosis and prognosis. Recently, MSP58 was shown to behave as an oncogene in colorectal carcinomas and gliomas. However, little is known about its function in esophageal carcinomas. We therefore examined the effects of MSP58 knockdown on the growth of esophageal squamous cell carcinoma (ESCC) cells in vitro and in vivo in order to gain a better understanding of its potential as a tumor therapeutic target. We employed lentiviral-mediated small hairpin RNA (shRNA) to knock down the expression of MSP58 in the ESCC cell lines Eca-109 and EC9706 and demonstrated inhibition of ESCC cell proliferation and colony formation in vitro. Furthermore, flow cytometry and western blot analyses revealed that MSP58 depletion induced cell cycle arrest by regulating the expression of P21, CDK4 and cyclin D1. Notably, the downregulation of MSP58 significantly inhibited the growth of ESCC xenografts in nude mice. Our results suggest that MSP58 may play an important role in ESCC progression.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.3
• /
• pp.1803-1806
• /
• 2013

Purpose: Carbohydrate antigen (CA) 242 is inversely related to prognosis in many cancers. However, few data regarding CA 242 in esophageal cancer (EC) are available. The aim of this study was to determine the prognostic value of CA 242 and propose an optimum cut-off point in predicting survival difference in patients with esophageal squamous cell carcinoma (ESCC). Methods: A retrospective analysis was conducted of 192 cases. A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimum cuf-off point. Univariate and multivariate analyses were performed to evaluate prognostic parameters for survival. Results: The positive rate for CA 242 was 7.3% (14/192). The ROC curve for survival prediction gave an optimum cut-off of 2.15 (U/ml). Patients with CA 242 ${\leq}$ 2.15 U/ml had significantly better 5-year survival than patients with CA 242 >2.15 U/ml (45.4% versus 22.6%; P=0.003). Multivariate analysis showed that differentiation (P=0.033), CA 242 (P=0.017), T grade (P=0.004) and N staging (P<0.001) were independent prognostic factors. Conclusions: Preoperative CA 242 is a predictive factor for long-term survival in ESCC, especially in nodal-negative patients. We conclude that 2.15 U/ml may be the optimum cuf-off point for CA 242 in predicting survival in ESCC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.11
• /
• pp.5587-5591
• /
• 2012

Objective: This study was performed to evaluated the efficacy and safety of continuous infusional paclitaxel and 5-Fu as first-line chemotherapy in patients with advanced esophageal squamous cell cancer (ESCC). Methods: A total of 22 patients with advanced esophageal squamous cell cancer with no indications for surgery and radiation therapy, or recurrent patients were enrolled from October 2008 to November 2010. All were treated with PTX 20 $mg/m^2$ was administered through a 16 hours continuous intravenous infusion on days 1 to 3, 8 and 9. DDP 3.75 $mg/m^2$ was given on days 1 to 4 and 8 to 11, continuous infusional 5-FU over 24-hours on days 1 to 5 and 8 to 12 at a dose of 375 $mg/m^2$, and folacin 60 mg orally synchronized with 5-Fu. The treatment was repeated every 21 days for at least two cycles. Results: 22 cases of all enrolled patients could be evaluated for the effect of treatment: 2 cases were CR, 9 cases PR, 5 cases SD and 2 cases PD, giving an overall response rate of 68.2%(15/22). The median time to progression was 7.0 months. The adverse reactions related to chemotherapy were tolerable; the most common toxic effects were marrow depression, alopecia, and fatigue. Conclusion: Low-dose continuous infusional PTX over 16-hours and 5-fu over 24-hours is a promising regimen with good tolerability in treating patients with advanced esophageal squamous cell cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.9
• /
• pp.4217-4222
• /
• 2016

Purpose: To compare the expression level of CK 15 in normal esophageal and esophageal squamous-cell carcinoma (ESCC) tissues and analyse possible functions of CK15 in occurrence and development. Materials and Methods: Immunohistochemistry was used to compare CK14, CK15 and proliferating cell nuclear antigen (PCNA) expression levels in ESCCs. Expression level of CK15 was also assessed by Western blotting. In addition, levels of CK15, cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and PCNA were detected in serum by enzymelinked immunosorbent assay (ELISA) and chemiluminescence methods. Relationships between clinicopathological parameters and CK14 and CK15 expression were then analyzed. Results: According to immunohistochemistry, in esophageal and intraepithelial neoplasia (SIN) tissues, the expression of CK14, CK15 and PCNA localized to basal layer of the epithelium. CK14 and CK15 levels were higher in normal esophageal squamous epithelial tissue than in SIN and ESCC, and greater in highly differentiated than poorly differentiated carcinoma tissue. By Western blotting, we found more pronounced expression of CK15 in normal esophageal tissue, compared with carcinoma tissue. The specificity of changed CK15 and CYFRA21-1 expression was respectively 90.0% and 96.7% in serum of ESCC patients. Joint detection could improve the sensitivity of esophageal carcinoma diagnosis. Relationships between CK14, CK15 expression and clinical parameters were not statistically significant (P>0.05). Postoperative survival in patients of CK14, CK15 positive expression was longer than with negative expression ($x^2=4.35$, P=0.037; $x^2=9.852$, P=0.002). Conclusions: CK15 expression decreased in esophageal squamous cell carcinoma tissue and serum of esophageal squamous carcinoma patients. We infer that CK15 may play an important role for the occurrence and development of esophageal squamous-cell carcinoma. In the future, CK15 may be used for the diagnosis, treatment and prognostic evaluation of esophageal squamous-cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.10
• /
• pp.5303-5306
• /
• 2012

Aim: The present case-control study was conducted to explore the association of MTHFR gene polymorphism and relations of P16, MGMT and HMLH1 to MTHFR and folate intake. Methods: A total of 257 cases of esophageal squamous cell carcinoma confirmed by histopathological examination were collected. Genotyping of P16, MGMT and HMLH1 was accomplished by methylation-specific polymerase chain reaction (PCR) after sodium bisulfate modification of DNA and the MTHFR C677T genetic polymorphism was detected by PCR-restriction fragment-length polymorphism (PCR-RFLP). Results: The proportions of DNA hypermethylation in P16, MGMT and hMLH1 in cancer tissues were significantly higher than in paracancerous normal tissue. The proportion of hypermethylation in at least one gene was 88.5% in cancer tissue, and was also significantly higher than that in paracancerous normal tissue. Our finding showed individuals with homozygotes (TT) of MTHFR C677T had significant risk of DNA hypermethylation of MGMT in cancer tissues, with an OR (95% CI) of 3.15 (1.12-6.87). Similarly, patients with high intake of folate also showed a slight high risk of DNA methylation of MGMT, with OR (95% CI) of 2.03 (1.05-4.57). Conclusion: Our study found the P16, MGMT and hMLH1 demonstrate a high proportion of hypermethylation in esophageal squamous cell cancer cancer tissues, which might be used as biomarkers for cancer detection.

• Journal of Microbiology and Biotechnology
• /
• v.32 no.6
• /
• pp.718-729
• /
• 2022

Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy with poor prognosis. Here, due to the necessity for exploring potential therapies against ESCC, we obtained the gene expression data on ESCC from the TCGA and GEO databases. Venn diagram analysis was applied to identify common targets. The protein-protein interaction network was constructed by Cytoscape software, and the hub targets were extracted from the network via cytoHubba. The potential hub nodes as drug targets were found by pharmacophore-based virtual screening and molecular modeling, and the antitumor activity was evaluated through in vitro studies. A total of 364 differentially expressed genes (DEGs) in ESCC were identified. Pathway enrichment analyses suggested that most DEGs were mainly involved in the cell cycle. Three hub targets were retrieved, including CENPF, CCNA2 (cyclin A), and CCNB1 (cyclin B1), which were highly expressed in esophageal cancer and associated with prognosis. Moreover, amentoflavone, a promising drug candidate found by pharmacophore-based virtual screening, showed antiproliferative and proapoptotic effects and induced G1 in esophageal squamous carcinoma cells. Taken together, our findings suggested that amentoflavone could be a potential cell cycle inhibitor targeting cyclin B1, and is therefore expected to serve as a great therapeutic agent for treating esophageal squamous cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.20
• /
• pp.8679-8684
• /
• 2014

CD133 was recently reported to be a cancer stem cell and prognostic marker. Quercetin is considered as a potential chemopreventive agent due to its involvement in suppression of oxidative stress, proliferation and metastasis. In this study, the expression of CD133/CD44 in esophageal carcinomas and Eca109/9706 cells was explored. In immunoflurorescence the locations of $CD133^+$ and multidrug resistance 1 $(MDR1)^+$ in the same E-cancer cells were coincident, mainly in cytomembranes. In esophageal squamous cell carcinomas detected by double/single immunocytochemistry, small $CD133^+$ cells were located in the basal layer of stratified squamous epithelium, determined as CSLC (cancer stem like cells); $CD44^+$ surrounding the cells appeared in diffuse pattern, and the larger $CD44^+$ (hi) cells were mainly located in the prickle cell layer of the epithelium, as progenitor cells. In E-cancer cells exposed to nanoliposomal quercetin (nLQ with cytomembrane permeability), down-regulation of NF-${\kappa}Bp65$, histone deacetylase 1 (HDAC1) and cyclin D1 and up-regulation of caspase-3 were shown by immunoblotting, and attenuated HDAC1 with nuclear translocation and promoted E-cadherin expression were demonstrated by immunocytochemistry. In particular, enhanced E-cadherin expression reflected the reversed epithelial mesenchymal transition (EMT) capacity of nLQ, acting as cancer attenuator/preventive agent. nLQ acting as an HDAC inhibitor induced apoptotic cells detected by TUNEL assay mediated via HDAC-NF-${\kappa}B$ signaling. Apoptotic effects of liposomal quercetin (LQ, with cytomembrane-philia) combined with CD133 antiserum were also detected by CD133 immunocytochemistry combined with TUNEL assay. The combination could induce greater apoptotic effects than nLQ induced alone, suggesting a novel anti-CSC treatment strategy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.8
• /
• pp.3519-3524
• /
• 2014

Background: Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. It has been hypothesized that Oct4 positive radioresistant stem cells may be responsible for tumor recurrence. Hence, we evaluated Oct4 expression in ESCC in pre-treatment, post neo-adjuvant residual and post-surgical recurrent tumours. Materials and Methods: Endoscopic mucosal biopsies were used to study Oct4 expression and the observations were correlated with histological tumor grades, patient data and clinical background. Results: All patients presented with dysphagia with male predominance and a wide age range. Majority of the patients had intake of mixed diet, history of alcohol and tobacco intake was documented in less than half of the patients. Oct 4 expression was significantly higher in poorly differentiated (PDSCC) and basaloid (BSCC) subtypes than the other better differentiated tumor morphology. Oct4 was also expressed by adjoining esophageal mucosa showing low grade dysplasia and basal cell hyperplasia (BCH). Biopsies in PDSCC and BSCC groups were more likely to show a positive band for Oct4 by polymerase chain reaction (PCR). Dysplasia and BCH mucosa also showed Oct4 positivity by PCR. All mucosal biopsies with normal morphology were negative for Oct4. Number of tissue samples showing Oct4 positivity by PCR was higher than that by the conventional immunohistochemistry (p>0.05). Oct4 expression pattern correlated only with tumor grading, not with other parameters including the clinical background or patient data. Conclusions: Our observations highlighted a possible role of Oct4 in identifying putative cancer stem cells in ESCC pathobiology and response to treatment. The implications are either in vivo existence of Oct4 positive putative cancer stem cells in ESCC or acquisition of cancer stem cell properties by tumor cells as a response to treatment given, resulting ultimately an uncontrolled cell proliferation and treatment failure.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.13
• /
• pp.5169-5173
• /
• 2015

To determine the efficacy of postoperative adjuvant chemotherapy with paclitaxel plus cisplatin (Taxol + DDP, TP therapy) for stage IIA esophageal squamous cell carcinoma (ESCC) and to investigate the expression of RUNX3 in lymph node metastasis-negative esophageal cancer and its relationship with medical prognosis, a retrospective summary of clinical treatment of 143 cases of stage IIA esophageal squamous cell carcinoma patients was made. The patients were divided into two groups, a surgery alone control group (52 patients) and a chemotherapy group that received postoperative TP therapy (91 patients). The disease-free and 5 year survival rates were compared between the groups and a multivariate analysis of prognostic factors was performed. The same analysis was performed for cases classified as RUNX3 positive and negative, with post-operative specimens assessed by immunohistochemistry. Although the disease-free and 5 year survival rates in control and chemotherapy groups did not significantly differ and there was no significance in RUNX3 negative cases, postoperative adjuvant chemotherapy in the chemotherapy group was shown to improve disease-free and 5 year survival rate compared to the control group in RUNX3 positive cases. On Cox regression multivariate analysis, postoperative adjuvant chemotherapy (P<0.01) was an independent prognostic factor for RUNX3 positive cases, suggesting that postoperative TP may be effective as adjuvant chemotherapy for stage IIA esophageal cancer patients with RUNX3 positive lesions.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.2919-2923
• /
• 2013

Esophageal cancer (EC) is one of the most common malignant tumors, and the incidence of esophageal squamous cell carcinoma (ESCC) is highest in China. Early diagnosis and effective monitoring are keys to comprehensive treatment and discovering tumor metastases and recurrence in time. The aim of this study was to confirm serum peptidome pattern utility for diagnosis of ESCC, and assessment of operation success, postoperative chemotherapy results, tumor metastasis and recurrence. Serum samples were collected from 61 patients treated with surgery and chemotherapy and 20 healthy individuals. Spectral data generated with weak cationic-exchanger magnetic beads (WCX-MB) and MALDI-TOF MS by a support vector machine (SVM), were used to construct diagnostic models and system training as potential biomarkers. A pattern consisting of 11 protein peaks, separated ESCC (m/z 650.75), operated (m/z 676.61, 786.1, 786.58), postoperative chemotherapy (m/z 622.77, 650.66, 676.46) and tumor metastasis and recurrence (m/z 622.63, 650.56, 690.77, 676.12) from the healthy individuals with a sensitivity of 100.0% and a specificity of 100.0%. These results suggested that MALDITOF MS combined with MB separation yields significantly higher sensitivity and specificity for the detection of serum protein in patients with EC patients treated with surgery and chemotherapy.