• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7221-7227
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• 2013

Background: Fascin, an actin-bundling protein forming actin bundles including filopodia and stress fibers, is overexpressed in multiple human epithelial cancers including esophageal squamous cell carcinoma (ESCC). Previously we conducted a microarray experiment to analyze fascin knockdown by RNAi in ESCC. Method: In this study, the differentially expressed genes from mRNA expression profilomg of fascin knockdown were analyzed by multiple bioinformatics methods for a comprehensive understanding of the role of fascin. Results: Gene Ontology enrichment found terms associated with cytoskeleton organization, including cell adhesion, actin filament binding and actin cytoskeleton, which might be related to fascin function. Except GO categories, the differentially expressed genes were annotated by 45 functional categories from the Functional Annotation Chart of DAVID. Subpathway analysis showed thirty-nine pathways were disturbed by the differentially expressed genes, providing more detailed information than traditional pathway enrichment analysis. Two subpathways derivated from regulation of the actin cytoskeleton were shown. Promoter analysis results indicated distinguishing sequence patterns and transcription factors in response to the co-expression of downregulated or upregulated differentially expressed genes. MNB1A, c-ETS, GATA2 and Prrx2 potentially regulate the transcription of the downregulated gene set, while Arnt-Ahr, ZNF42, Ubx and TCF11-MafG might co-regulate the upregulated genes. Conclusions: This multiple bioinformatic analysis helps provide a comprehensive understanding of the roles of fascin after its knockdown in ESCC.

• Journal of Chest Surgery
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• v.51 no.3
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• pp.187-194
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• 2018

Background: Death domain-associated protein (DAXX), originally identified as a pro-apoptotic protein, is now understood to be either a pro-apoptotic or an anti-apoptotic factor with a chromatin remodeler, depending on the cell type and context. This study evaluated DAXX expression and its clinical implications in squamous cell carcinoma of the esophagus. Methods: Paraffin-embedded tissues from 60 cases of esophageal squamous carcinoma were analyzed immunohistochemically. An immune reaction with more than 10% of tumor cells was interpreted as positive. Positive reactions were sorted into 2 groups: reactions in 11%-50% of tumor cells and reactions in more than 51% of tumor cells, and the correlations between expression and survival and clinical prognosticators were analyzed. Results: Forty-three of the 60 cases (71.7%) showed strong nuclear DAXX expression, among which 19 cases showed a positive reaction (31.7%) in 11%-50% of tumor cells, and 24 cases (40.0%) showed a positive reaction in more than 51% of tumor cells. A negative reaction was found in 17 cases (28.3%). These patterns of immunostaining were significantly associated with the N stage (p=0.005) and American Joint Committee on Cancer stage (p=0.001), but overall survival showed no significant difference. There were no correlations of DAXX expression with age, gender, or T stage. However, in stage IIB (p=0.046) and stage IV (p=0.014) disease, DAXX expression was significantly correlated with survival. Conclusion: This investigation found upregulation of DAXX in esophageal cancer, with a 71.7% expression rate. DAXX immunostaining could be used in clinical practice to predict aggressive tumors with lymph node metastasis in advanced-stage disease, especially in stages IIB and IV.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5445-5451
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• 2015

Fascin-1 (FSCN1) is an actin-bundling protein that induces cell membrane protrusions, increases cell motility, and is overexpressed in various human epithelial cancers, including esophageal squamous cell carcinoma (ESCC). We analyzed various protein-protein interactions (PPI) of differentially-expressed genes (DEGs), in fascin knockdown ESCC cells, to explore the role of fascin overexpression. The node-degree distributions indicated these PPI sub-networks to be characterized as scale-free. Subcellular localization analysis revealed DEGs to interact with other proteins directly or indirectly, distributed in multiple layers of extracellular membrane-cytoskeleton/ cytoplasm-nucleus. The functional annotation map revealed hundreds of significant gene ontology (GO) terms, especially those associated with cytoskeleton organization of FSCN1. The Random Walk with Restart algorithm was applied to identify the prioritizations of these DEGs when considering their relationship with FSCN1. These analyses based on PPI network have greatly expanded our comprehension of the mRNA expression profile following fascin knockdown to future examine the roles and mechanisms of fascin action.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3075-3079
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• 2014

Background: The relationship between body mass index(BMI) and outcomes after chemoradiotherapy(CRT) has not been systematically addressed. The purpose of this study was to evaluate the effect of BMI on survival in patients with esophageal squamous cell carcinoma (ESCC). Materials and Methods: Sixty ESCC cases were retrospectively reviewed in this study. Patient overall survival(OS) and disease-free survival (DFS) were compared between two groups (BMI< $24.00kg/m^2$ and $BMI{\geq}24.00kg/m^2$). Results: There were 41 patients in the low/normal BMI group (BMI< $24.00kg/m^2$) and 19 in the high BMI group ($BMI{\geq}24.00kg/m^2$). No significant differences were observed in patient characteristics between these. We found no difference in 2-year OS and DFS associated with BMI (p=0.763 for OS; p=0.818 for DFS) using the Kaplan-Meier method. Univariate analysis revealed that higher clinical stage was prognostic for worse 2-year OS and DFS, metastasis for 2-year OS, lymph node status for 2-year DFS, while age, gender, smoking, drinking, tumor location and BMI were not prognostic. There were no differences in the 2-year OS (hazard ratio=1.117; p=0.789) and DFS(hazard ratio=1.161; p=0.708) between BMI groups in multivariate analysis, whereas we found statistical differences in the 2-year OS and DFS associated with clinical stage, gender and tumor infiltration (p<0.04), independent of age, smoking, drinking, tumor location, the status of lymph node metastases and BMI. Conclusions: BMI was not associated with survival in patients with ESCC treated with CRT as primary therapy. BMI should not be considered a prognostic factor for patients undergoing CRT for ESCC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.767-773
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• 2012

The esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with a poor prognosis. Understanding molecular changes in ESCC should improve identification of risk factors with different molecular subtypes and provide potential targets for early detection and therapy. Our study aimed to obtain a molecular signature of ESCC through the regulation network based on differentially expressed genes (DEGs). We used the GSE23400 series to identify potential genes related to ESCC. Based on bioinformatics we constructed a regulation network. From the results, we could establish that many transcription factors and pathways closely related with ESCC were linked by our method. STAT1 also arose as a hub node in our transcriptome network, along with some transcription factors like CCNB1, TAP1, RARG and IFITM1 proven to be related with ESCC by previous studies. In conclusion, our regulation network provided information on important genes which might be useful in investigating the complex interacting mechanisms underlying the disease.

• Journal of Pharmacopuncture
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• v.22 no.2
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• pp.102-108
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• 2019

Objectives: Esophageal squamous cell carcinoma (ESCC) is considered as a deadly medical condition that affects a growing number of people worldwide. Targeted therapy of ESCC has been suggested recently and required extensive research. With cyclin D1 as a therapeutic target, the present study aimed at evaluating the anticancer effects of doxorubicin (Dox) or Hypericum perforatum L. (HP) extract encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on the ESCC cell line KYSE30. Methods: Nanoparticles were prepared using double emulsion method. Cytotoxicity assay was carried out to measure the anti-proliferation activity of Dox-loaded (Dox NPs) and HP-loaded nanoparticles (HP NPs) against both cancer and normal cell lines. The mRNA gene expression of cyclin D1 was evaluated to validate the cytotoxicity studies at molecular level. Results: Free drugs and nanoparticles significantly inhibited KYSE30 cells by 55-73% and slightly affected normal cells up to 29%. The IC50 of Dox NPs and HP NPs was ~ 0.04-0.06 mg/mL and ~ 0.6-0.7 mg/mL, respectively. Significant decrease occurred in cyclin D1 expression by Dox NPs and HP NPs (P < 0.05). Exposure of KYSE-30 cells to combined treatments including both Dox and HP extract significantly increased the level of cyclin D1 expression as compared to those with individual treatments (P < 0.05). Conclusion: Dox NPs and HP NPs can successfully and specifically target ESCC cells through downregulation of cyclin D1. The simultaneous use of Dox and HP extract should be avoided for the treatment of ESCC.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.61-73
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• 2023

Esophageal squamous cell carcinoma (ESCC) is a kind of malignant tumor with high incidence and mortality in the digestive system. The aim of this study is to explore the function of lnc-ABCA12-3 in the development of ESCC and its unique mechanisms. RT-PCR was applied to detect gene transcription levels in tissues or cell lines like TE-1, EC9706, and HEEC cells. Western blot was conducted to identify protein expression levels of mitochondrial apoptosis and toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway. CCK-8 and EdU assays were carried out to measure cell proliferation, and cell apoptosis was examined by flow cytometry. ELISA was used for checking the changes in glycolysis-related indicators. Lnc-ABCA12-3 was highly expressed in ESCC tissues and cells, which preferred it to be a candidate target. The TE-1 and EC9706 cells proliferation and glycolysis were obviously inhibited with the downregulation of lnc-ABCA12-3, while apoptosis was promoted. TLR4 activator could largely reverse the apoptosis acceleration and relieved the proliferation and glycolysis suppression caused by lnc-ABCA12-3 downregulation. Moreover, the effect of lnc-ABCA12-3 on ESCC cells was actualized by activating the TLR4/NF-κB signaling pathway under the mediation of exosome. Taken together, the lnc-ABCA12-3 could promote the proliferation and glycolysis of ESCC, while repressing its apoptosis probably by regulating the TLR4/NF-κB signaling pathway under the mediation of exosome.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5437-5442
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• 2014

Esophageal squamous cell carcinoma (ESCC) is one of the most malignancies with a poor prognosis. The phospholipase $C{\varepsilon}$ gene (PLCE1) encodes a novel ras-related protein effector mediating the effects of R-Ras on the actin cytoskeleton and membrane protrusion. However, molecular mechanisms pertinent to ESCC are unclear. We therefore designed PLCE1-special small interfering RNA and transfected to esophageal squamous cell (EC) 9706 cells to investigat the effects of PLCE1 gene silencing on the cell cycle and apoptosis of ESCC and indicate its important role in the development of ESCC. Esophageal cancer tissue specimens and normal esophageal mucosa were obtained and assayed by immunohistochemical staining to confirm overexpression of PLCE1 in neoplasias. Fluorescence microscopy was used to examine transfection efficiency, while the result of PLCE1 silencing was examined by reverse transcription (RT-PCR). Flow cytometry and annexin V apoptosis assays were used to assess the cell cycle and apoptosis, respectively. Expression of cyclin D1 and caspase-3 was detected by Western-blotting. The level of PLCE1 protein in esophageal cancer tissue was significantly higher than that in normal tissue. After transfection, the expression of PLCE1 mRNA in EC 9706 was significantly reduced, compared with the control group. Furthermore, flow cytometry results suggested that the PLCE1 gene silencing arrested the cell cycle in the G0/G1 phase; apoptosis was significantly higher than in the negative control group and mock group. PLCE1 gene silencing by RNAi resulted in decreased expression of cyclin D1 and increased expression of caspase-3. Our study suggests that PLCE1 may be an oncogene and play an important role in esophageal carcinogenesis through regulating proteins which control cell cycling and apoptosis.

• Journal of Digestive Cancer Research
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• v.1 no.1
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• pp.53-57
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• 2013

There is no established treatment for esophageal carcinoma with metastasis. For the metastatic esophageal squamous cell carcinoma, chemotherapy or best supportive care according to patient's performance status are accepted as an available treatment. We report a case of complete remission after concurrent chemoradiotherapy for esophageal squamous cell carcinoma with metastatic lesion in 5th thoracic vertebrae. A 57-year-old man with ongoing dysphagia and weight loss was admitted to our hospital. On the endoscopic and radiologic imaging evaluation,the patient was diagnosed as a squamous cell carcinoma of esophagus with solitary metastatic lesion in 5th thoracic vertebrae. The patient was treated with combination chemotherapy (5-fluorouracil (5-FU) and cisplatin) and concurrent radiotherapy for two months to relieve dysphagia. Because metastatic lesion in thoracic vertebrae was located near the primary esophageal tumor, the metastatic lesion could be included within the radiation field. After concurrent chemoradiotherapy, consecutive 4 cycles of chemotherapy had been carried out. Primary esophageal tumor with metastatic lymph nodes and metastatic lesion in 5th thoracic vertebrae disappeared on follow up computed tomography (CT) and positron emission tomography-CT (PET-CT). Follow up endoscopic biopsy revealed no remnant malignant cells at previous primary cancer lesion.

• Journal of Life Science
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• v.21 no.3
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• pp.417-423
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• 2011

Thymosin ${\beta}4$ (TB-4) has been reported to play a key role in tumor growth, metastasis and angiogenesis. In addition, TB-4 induced the expression of vascular endothelial growth factor (VEGF) and stabilized the hypoxia-inducible factor (HIF)-$1{\alpha}$ in melanoma cells. Although the importance of thymosin ${\beta}4$ in angiogenesis and metastasis has been proven, there are few studies that show the expression patterns of TB-4, VEGF and HIF-$1{\alpha}$. This study was conducted to analyze the relationship among these proteins in various tumors. Using tissue microarray analysis, we investigated the expression patterns of TB-4, VEGF and HIF-$1{\alpha}$ in various tumors to identify the expression patterns and relationships of these proteins in certain tumors. TB-4 was highly expressed in osteosarcoma, colon adenocarcinoma, esophageal squamous cell carcinoma, kidney and urinary bladder transitional carcinoma, lung cancer, and liver cancer. HIF-$1{\alpha}$ was highly expressed in nasal cavity inverted papilloma, lung cancer, and esophageal squamous cell carcinoma. The expression patterns of TB-4 and HIF-$1{\alpha}$ were almost similar and co-localized. VEGF expression was high in the blood vessels in tumors, but usually not high in the tumors themselves. VEGF was moderately expressed in stomach cancer, liver angiosarcoma, gall bladder adenocarcinoma, and uterus endometrial adenocarcinoma. The expression patterns of VEGF shows similarities in certain tumors including stomach cancer, osteosarcoma, liposarcoma, lung cancer, liver cancer, gall bladder adenocarcinoma, esophageal squamous cell carcinoma, stomach cancer, colorectal carcinoma and renal cell carcinoma. These results suggest that the expression patterns of TB-4, HIF-$1{\alpha}$ and VEGF were co-localized and related to tumorigenesis and angiogenesis of certain tumors.