Effects of Down-regulation of HDAC6 Expression on Proliferation, Cell Cycling and Migration of Esophageal Squamous Cell Carcinoma Cells and Related Molecular Mechanisms

Li, Ning,Tie, Xiao-Jing,Liu, Pei-Jie,Zhang, Yan,Ren, Hong-Zheng,Gao, Xin,Xu, Zhi-Qiao Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Objective: To study the effects of down-regulation of HDAC6 expression on proliferation, cell cycling and migration of esophageal squamous cell carcinoma (ESCC) cells and related molecular mechanisms. Methods: ESCC cell line EC9706 cells were randomly divided into untreated (with no transfection), control siRNA (transfected with control siRNA) and HDAC6 siRNA (transfected with HDAC6 small interfering RNA) groups. Effects of HDAC6 siRNA interference on expression of HDAC6 mRNA and protein in EC9706 cells were investigated by semi-quantitative RT-PCR, Western blotting and immunocytochemistry methods. Effects of down-regulation of HDAC6 expression on cell proliferation, cell cycle, and cell migration were studied using a CCK-8 kit, flow cytometry and Boyden chambers, respectively. Changes of mRNA and protein expression levels of cell cycle related factor (p21) and cell migration related factor (E-cadherin) were investigated by semi-quantitative RT-PCR and Western blotting methods. Results: After transfection of HDAC6 siRNA, the expression of HDAC6 mRNA and protein in EC9706 cells was significantly downregulated. In the HDAC6 siRNA group, cell proliferation was markedly inhibited, the percentage of cells in G0/G1 phase evidently increased and the percentage of cells in S phase decreased, and the number of migrating cells significantly and obviously decreased. The mRNA and protein expression levels of p21 and E-cadherin in the HDAC6 siRNA group were significantly higher than those in the untreated group and the control siRNA group, respectively. Conclusions: HDAC6 siRNA can effectively downregulate the expression of HDAC6 mRNA and protein in EC9706 cells. Down-regulation of HDAC6 expression can obviously inhibit cell proliferation, arrest cell cycling in the G0/G1 phase and reduce cell migration. The latter two functions may be closely related with the elevation of mRNA and protein expression of p21 and E-cadherin.

식도 암육종 환자에서 이시적으로 발생한 식도 편평상피세포암

차라리 ( Ra Ri Cha ),정운태 ( Woon Tae Jung ),오혜원 ( Hye Won Oh ),김희진 ( Hee Jin Kim ),하창윤 ( Chang Yoon Ha ),김홍준 ( Hong Jun Kim ),김태효 ( Tae Hyo Kim ),고경혁 ( Gyung Hyuck Ko ) 대한소화기학회 2014 대한소화기학회지 Vol.64 No.6

Esophageal carcinosarcoma is a rare malignant esophageal neoplasm consisting of both carcinomatous and sarcomatous elements, with an incidence of 0.5%. There have been only a few case reports of carcinosarcoma and squamous cell carcinoma coexisting in the esophagus. However, all of these are cases of synchronous or metachronous development of carcinosarcoma after chemoradiotherapy in patients of esophageal squamous cell carcinoma. A 53-year-old man underwent esophagogastroduodenoscopy because of chest pain for several months. Endoscopic examination revealed a huge pedunculated esophageal polypoid mass. Endoscopic submucosal dissection (ESD) was performed and histopathologic examination confirmed spindle cell carcinoma (carcinosarcoma). He refused additional esophagectomy. After 21 months, third follow-up endoscopy showed poorly-demarcated flat, faint discolored lesions at different location from the previous ESD site and endoscopic biopsies confirmed squamous cell carcinoma. To the best of our knowledge, this is the first case of metachronous development of esophageal squamous cell carcinoma in a patient with esophageal carcinosarcoma. (Korean J Gastroenterol 2014;64:364-369)

식도암에서 전이된 편평상피세포암 1예

김철우,김영진,김수영,남상호,이종주 대한피부과학회 2002 대한피부과학회지 Vol.40 No.8

We report a case of squamous cell carcinoma originating from esophageal carcinoma. 2×3㎝ sized, flesh-colored, soft, movable nodules were detected on the scalp in a 59-year-old man. He was made a diagnosis of squamous cell carcinoma in the distal esophagus a year ago. Histopathologic examination showed that the tumor had multiple mitoses and horn pearls, but there was no connection between the epidermis and the tumor nests. In immunohistochemical stains, cytokeratin-high molecular weight and EMA was positive, but CEA was negative.

The Current Evidence on Neoadjuvant Therapy for Locally Advanced Esophageal Squamous Cell Carcinoma

오동렬,김종훈 대한흉부외과학회 2020 Journal of Chest Surgery (J Chest Surg) Vol.53 No.4

Surgical resection is the mainstay of treatment for locally advanced esophageal cancer. Neoadjuvant therapy is recommended to improve survival, based on the results of several randomized trials and meta-analyses. However, controversy remains regarding how to combine surgery, radiotherapy, and chemotherapy. Moreover, in East Asia, the pre- dominant histological type is esophageal squamous cell carcinoma, which has a different epidemiology and tumor biology from esophageal or gastroesophageal junctional adenocarcinoma. As such, the management of esophageal cancer in East Asia seems to be different from that in Western countries. Thus, this article reviews the current evidence on neoadjuvant therapy and considers the optimal combinations and ongoing strategies of multimodal therapy for esophageal squamous cell carcinoma.

Long-Term Outcome after Endoscopic Submucosal Dissection in Patients with Superficial Esophageal Squamous Cell Carcinoma: A Single-Center Study

( Dong Chan Joo ),( Gwang Ha Kim ),( Do Youn Park ),( Joon Hyung Jhi ),( Geun Am Song ) 대한소화기학회 2014 Gut and Liver Vol.8 No.6

Background/Aims: Superficial esophageal squamous cell carcinoma (SESCC) is being increasingly detected during screening endoscopy. Endoscopic submucosal dissection (ESD) allows for en bloc and histologically complete resection of lesions. This study assessed the technical feasibility and long-term outcomes of ESD for SESCCs. Methods: Between January 2005 and August 2012, 27 patients with 28 SESCCs underwent ESD at Pusan National University Hospital. The en bloc and pathologically complete resection rates, complication (perforation and bleeding) rate, incidence of esophageal stricture after ESD, and overall and disease-specific survival rates were evaluated. Results: The en bloc and pathologically complete resection rates were 93% and 83%, respectively. No significant bleeding occurred, and perforation with mediastinal emphysema was observed in two patients (7%). Post- ESD stricture occurred in two patients (7%) who had mucosal defects involving more than three-fourths of the esophageal circumference. During a mean follow-up of 23 months, local tumor recurrence was seen in two of four lesions with pathologically incomplete resection; one was treated by re-ESD, and the other was treated by surgical esophagectomy. The 5-year overall and disease-specific survival rates were 84% and 100%, respectively. Conclusions: ESD seems to be a feasible, effective curative treatment for SESCCs. All patients should be closely followed after ESD. (Gut Liver 2014;8:612- 618)

MSP58 Knockdown Inhibits the Proliferation of Esophageal Squamous Cell Carcinoma in Vitro and in Vivo

Xu, Chun-Sheng,Zheng, Jian-Yong,Zhang, Hai-Long,Zhao, Hua-Dong,Zhang, Jing,Wu, Guo-Qiang,Wu, Lin,Wang, Qing,Wang, Wei-Zhong,Zhang, Jian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

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.

Downregulation of HuR Inhibits the Progression of Esophageal Cancer through Interleukin-18

Xu Xiaohui,Song Cheng,Chen Zhihua,Yu Chenxiao,Wang Yi,Tang Yiting,Luo Judong 대한암학회 2018 Cancer Research and Treatment Vol.50 No.1

Purpose The purpose of this study was to investigate the effect of human antigen R (HuR) downregulation and the potential target genes of HuR on the progression of esophageal squamous cell carcinoma (ESCC). Materials and Methods In this study, a proteomics assay was used to detect the expression of proteins after HuR downregulation, and a luciferase assay was used to detect the potential presence of a HuR binding site on the 3’-untranslated region (3'-UTR) of interleukin 18 (IL-18). In addition, colony formation assay, MTT, EdU incorporation assay, Western blot, flow cytometry, immunohistochemistry, transwell invasion assay, and wound healing assay were used. Results In the present study, we found that the expression of both HuR protein and mRNA levels were higher in tumor tissues than in the adjacent tissues. HuR downregulation significantly suppressed cell proliferation. In addition, the metastasis of esophageal cancer cells was inhibited, while the expression of E-cadherin was increased and the expression of matrix metalloproteinase (MMP) 2, MMP9, and vimentin was decreased after HuR knockdown. Moreover, silencing of HuR disturbed the cell cycle of ESCC cells mainly by inducing G1 arrest. Furthermore, proteomics analysis showed that downregulation of HuR in TE-1 cells resulted in 100 upregulated and 122 downregulated proteins, including IL-18 as a significantly upregulated protein. The expression of IL-18 was inversely regulated by HuR. IL-18 expression was decreased in ESCC tissues, and exogenous IL-18 significantly inhibited the proliferation and metastasis of ESCC cells. The 3'-UTR of IL-18 harbored a HuR binding site, as shown by an in vitro luciferase assay. Conclusion HuR plays an important role in the progression of esophageal carcinoma by targeting IL-18, which may be a potential therapeutic target for the treatment of ESCC.

Patterns of Lymph Node Recurrence after Radical Surgery Impacting on Survival of Patients with pT1-3N0M0 Thoracic Esophageal Squamous Cell Carcinoma

Xiao-li Chen,,Tian-wu Chen,Zhi-jia Fang,Xiao-ming Zhang,Zhen-lin Li,Hang Li,Hong-jie Tang,Li Zhou,Dan Wang,Zishu Zhang 대한의학회 2014 Journal of Korean medical science Vol.29 No.2

The aim of this study was to investigate how patterns of lymph nodes recurrence after radical surgery impact on survival of patients with pT1-3N0M0 thoracic esophageal squamous cell carcinoma. One hundred eighty consecutive patients with thoracic esophageal squamous cell carcinoma underwent radical surgery, and the tumors were staged as pT1-3N0M0 by postoperative pathology. Lymph nodes recurrence was detected with computed tomography 3-120 months after the treatment. The patterns of lymph nodes recurrence including stations, fields and locations of recurrent lymph nodes, and impacts on patterns of survival were statistically analyzed. There was a decreasing trend of overall survival with increasing stations or fields of postoperative lymph nodes involved (all P<0.05). Univariate analysis showed that stations or fields of lymph nodes recurrence, and abdominal or cervical lymph nodes involved were prognostic factors for survival(all P<0.05). Cox analyses revealed that the field was an independent factor (P<0.05, odds ratio=2.73). Lymph nodes involved occurred predominantly in cervix and upper mediastinum (P<0.05). In conclusion, patterns of lymph node recurrence especially the fields of lymph nodes involved are significant prognostic factors for survival of patients with pT1-3N0M0 thoracic esophageal squamous cell carcinoma.

Exosome-mediated lnc-ABCA12-3 promotes proliferation and glycolysis but inhibits apoptosis by regulating the toll-like receptor 4/nuclear factor kappa-B signaling pathway in esophageal squamous cell carcinoma

Junliang Ma,Yijun Luo,Yingjie Liu,Cheng Chen,Anping Chen,Lubiao Liang,Wenxiang Wang,Yongxiang Song 대한약리학회 2023 The Korean Journal of Physiology & Pharmacology Vol.27 No.1

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.

Association of High Expression of Mitochondrial Fission Regulator 2 with Poor Survival of Patients with Esophageal Squamous Cell Carcinoma

Hongwei Li,Xingzhuang Zhu,Wei Zhang,Wenjie Lu,Chuan Liu,Jinbo Ma,Rukun Zang,Yipeng Song 대한암예방학회 2021 Journal of cancer prevention Vol.26 No.4

Mitochondrial fission regulator 2 (MTFR2) is associated with mitochondrial fission, while few studies have assessed the associations between MTFR2 expression and clinical characteristics or prognosis of esophageal squamous cell carcinoma (ESCC). In this study, we compared the expression of MTFR2 in 6 ESCC tumors and relative normal tissues by immunohistochemistry (IHC). To assess the effect of MTFR2 expression on clinicopathologic characteristics and survival, 115 paraffin embedded ESCC tissue samples were assessed by IHC staining. Furthermore, the association between clinicopathological properties and MTFR2 expression in patients with ESCC was examined. The survival analysis was performed using the Cox regression models. We found that MTFR2 expression was significantly increased in ESCC tumors compared with normal esophageal epithelial cells. IHC analysis of 115 paraffin embedded ESCC tumor specimens of the patients showed that the expression of MTFR2 was significantly associated with clinical stage (P < 0.001), tumor classification (P < 0.001), histological grade (P < 0.001), and other clinicopathological characteristics. Both univariate and multivariate analyses showed that MTFR2 expression was inversely correlated with the survival of ESCC patients. In conclusion, the expression of MTFR2 is significantly associated with clinicopathologic characteristics and prognosis of ESCC. Thus, MTFR2 expression could serve as a potentially important prognostic biomarker and clinical target for patients with ESCC. Key Words MTFR2, Esophageal squamous cell carcinoma, Immunohistochemistry, Prognosis