• Journal of Chest Surgery
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• v.33 no.1
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• pp.112-115
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• 2000

A-13-urar-old with a history of Alport syndrome had been suffering from progressive dysphagia and postprandial vomiting for over 7 years. Exophagogram and manoemtric studies were consistent with achalasia. Barum study demonstrated marked esophageal dilatation and smooth tapered narrowing of the distal esophagus. However in spite of the medical treatment including the injection of the distal esophagus. However in spite of the medical treatment including the injection of botulinum toxin at the lesion site using an endoscope symptom did not improved and he suffered growth failure and malnutrition. Esophagectomy and esophagogastrostomy were performed to relieve the dysphagia. A firm circumferential intramural mass about 7$\times$5$\times$5 cm was found in the distal esophagus. The lumen of the esophagus was markedly dilated and esophageal wall was hypertrophied. Histologic examination of the neoplasm revealed a rather ill defined tumor tissue consisting of interlacing or whirling spindle cells without significant mitosis and esophageal leiomyo-matosis was confirmed. The patient was discharged uneventfully.

• Journal of Microbiology and Biotechnology
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• v.32 no.6
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• pp.718-729
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• 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
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• v.13 no.1
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• pp.205-209
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• 2012

Background: The inhibition of tumor cell growth without toxicity to normal cells is an important target in cancer therapy. One possible way to increase the efficacy of anticancer drugs and to decrease toxicity or side effects is to develop traditional natural products, especially from medicinal plants. Paris polyphylla Smith has shown anti-tumour effects by inhibition of tumor promotion and inducement of tumor cell apoptosis, but mechanisms are still not well understood. The present study was to explore the effect of Paris polyphylla Smith extract (PPSE) on connexin26 and growth control in human esophageal cancer ECA109 cells. Methods: The effects of PPSE on Connexin26 were examined by RT-PCR, western blot and immunofluorescence; cell growth and proliferation were examined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Results: PPSE inhibited the growth and proliferation on esophageal cancer ECA109 cells, while increasing the expression of connexin26 mRNA and protein; conversely, PPSE decreased Bcl-2 and increased Bad. Conclusion: This study firstly shows that PPSE can increase connexin26 expression at mRNA and protein level, exerting anti-tumour effects on esophageal cacner ECA109 cells via inhibiting cell proliferation and inducing cell apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4147-4151
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• 2012

The current study was conducted to explore the inhibitory effects of a small interfering RNA (siRNA) on 3-phosphoinositide-dependent protein kinase 1 (PDK1) expression in esophageal cancer 9706 (EC9706) cells and the influence on their biological behavior. After transfection of a synthesized PDK1 siRNA, PDK1 mRNA and protein expression and the phosphorylation level of the downstream Akt protein were assessed using RT-PCR and Western blot analysis. Proliferation, apoptosis, cell invasion and in vivo tumor formation capacity were also investigated using MTT, flow cytometry, Transwell invasion trials, and nude mouse tumor transplantion, respectively. PDK1 siRNA effectively suppressed PDK1 mRNA and protein expression, and down-regulated the phosphorylation level of the Akt protein in the EC9706 cells (P < 0.05). It also inhibited cell proliferation and invasion, and promoted apoptosis; such effects were particularly obvious at 48 h and 72 h after transfection (P < 0.05). Growth of transplanted tumors was inhibited in nude mice, with decreased PDK1 expression in tumor tissues. PDK1 may be closely correlated with proliferation, apoptosis and invasion of esophageal cancer cells and thus may serve as an effective target for gene therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3015-3023
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• 2012

The mitochondrial antioxidant protein manganese superoxide dismutase (MnSOD) may represent a new type of tumor suppressor protein. Overexpression of the cDNA of this gene by plasmid or recombinant lentiviral transfection in various types of cancer leads to growth suppression both in vitro and in vivo. We previously determined that changes in MnSOD expression had bidirectional effects on adriamycin (ADR) when combined with nitric oxide (NO). Radiation induces free radicals in a manner similar to ADR, so we speculated that MnSOD combined with NO would also have a bidirectional effect on cellular radiosensitivity. To examine this hypothesis, TE-1 human esophageal squamous carcinoma cells were stably transfected using lipofectamine with a pLenti6-DEST plasmid containing human MnSOD cDNA at moderate to high overexpression levels or with no MnSOD insert. Blastidicin-resistant colonies were isolated, grown, and maintained in culture. We found that moderate overexpression of MnSOD decreased growth rates, plating efficiency, and increased apoptosis. However, high overexpression increased growth rates, plating efficiency, and decreased apoptosis. When combined with NO, moderate overexpression of MnSOD increased the radiosensitivity of esophageal cancer cells, whereas high MnSOD overexpression had the opposite effect. This finding suggests a potential new method to kill certain radioresistant tumors and to provide radioresistance to normal cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3519-3524
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• 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
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• v.14 no.9
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• pp.5391-5396
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• 2013

Aim: To investigate the role of Golgi phosphoprotein 3 (GOLPH3) in tumour growth and metastasis of esophageal squamous cancer. Methods: A lentiviral shRNA-vector was utilized to stably knockdown GOLPH3 in Eca-109 esophageal squamous cancer cells. mRNA transcription and protein expression of GOLPH3 were examined by real-time quantitative PCR and Western blotting, respectively. Cell proliferation activity was assessed by MTT assay and invasion and migration potentials by matrigel invasion and transwell motility assays. Results: Stable knockdown in the GOLPH3 cell line was established. PD-A gene expression was significantly suppressed by lentivirus-mediated RNAi, which resulted in reducing the capacity for cell proliferation, migration, invasion and adhesion in vitro. In vivo, GOLPH3 depletion resulted in inhibition of tumour growth, with stable decrease in the expression of GOLPH3 in tumor xenografts. Conclusions: Our findings suggest that lentivirus mediated silencing of the GOLPH3 gene has a significant anti-tumour effect on esophageal squamous cancer in vitro and in vivo. In addition, the results indicate that GOLPH3 might be an effective molecular target for gene therapy in esophageal squamous cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.139-147
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• 2013

Lysolipids such as LPA, S1P and SPC have diverse biological activities including cell proliferation, differentiation, and migration. We investigated signaling pathways of LPA-induced contraction in feline esophageal smooth muscle cells. We used freshly isolated smooth muscle cells and permeabilized cells from cat esophagus to measure the length of cells. Maximal contraction occurred at $10^{-6}M$ and the response peaked at 30s. To identify LPA receptor subtypes in cells, western blot analysis was performed with antibodies to LPA receptor subtypes. LPA1 and LPA3 receptor were detected at 50 kDa and 44 kDa. LPA-induced contraction was almost completely blocked by LPA receptor (1/3) antagonist KI16425. Pertussis toxin (PTX) inhibited the contraction induced by LPA, suggesting that the contraction is mediated by a PTX-sensitive G protein. Phospholipase C (PLC) inhibitors U73122 and neomycin, and protein kinase C (PKC) inhibitor GF109203X also reduced the contraction. The PKC-mediated contraction may be isozyme-specific since only $PKC{\varepsilon}$ antibody inhibited the contraction. MEK inhibitor PD98059 and JNK inhibitor SP600125 blocked the contraction. However, there is no synergistic effect of PKC and MAPK on the LPA-induced contraction. In addition, RhoA inhibitor C3 exoenzyme and ROCK inhibitor Y27632 significantly, but not completely, reduced the contraction. The present study demonstrated that LPA-induced contraction seems to be mediated by LPA receptors (1/3), coupled to PTX-sensitive G protein, resulting in activation of PLC, PKC-${\varepsilon}$ pathway, which subsequently mediates activation of ERK and JNK. The data also suggest that RhoA/ROCK are involved in the LPA-induced contraction.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.319-326
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• 2011

Quercetin-3-O-${\beta}$-D-glucuronopyranoside (QGC) is a flavonoid glucoside extracted from Rumex Aquaticus Herba. We aimed to explore its protective effect against ethanol-induced cell damage and the mechanism involved in the effect in feline esophageal epithelial cells (EEC). Cell viability was tested and 2',7'-dichlorofluorescin diacetate assay was used to detect intracellular $H_2O_2$ production. Western blotting analysis was performed to investigate MAPK activation and interleukin 6 (IL-6) expression. Exposure of cells to 10% ethanol time-dependently decreased cell viability. Notably, exposure to ethanol for 30 min decreased cell viability to 43.4%. When cells were incubated with $50{\mu}M$ QGC for 12 h prior to and during ethanol treatment, cell viability was increased to 65%. QGC also inhibited the $H_2O_2$ production and activation of ERK 1/2 induced by ethanol. Pretreatment of cells with the NADPH oxidase inhibitor, diphenylene iodonium, also inhibited the ethanol-induced ERK 1/2 activation. Treatment of cells with ethanol for 30 or 60 min in the absence or presence of QGC exhibited no changes in the IL-6 expression or release compared to control. Taken together, the data indicate that the cytoprotective effect of QGC against ethanol-induced cell damage may involve inhibition of ROS generation and downstream activation of the ERK 1/2 in feline EEC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6517-6521
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• 2012

To analyze the growth, proliferation, apoptosis, invasiveness and chemotherapy sensitivity of EC9706 cells after K-Ras gene silencing, an expression carrier pSilencer-siK-Ras was constructed, and the EC9706 cell line was transfected using a liposome technique. Six groups were established: Control, siRNA NC (transfected with empty vector pSilencer2.1); Ras siRNA (transfected with pSilencer-siK-Ras2); Paclitaxel; Paclitaxel + siRNA NC; and Ras siRNA + Paclitaxel. After the treatment, RT-PCR, Western blotting, MTT assay, flow cytometry and the Transwell technique were used to assess expression of K-Ras mRNA and protein in EC9706 cells, as well as cell growth, proliferation, apoptosis and invasiveness. The effect of Paclitaxel chemotherapy was also tested. pSilencer-siK-Ras2 effectively down-regulated expression of K-Ras mRNA and protein in EC9706 cells, growth being significantly inhibited. Flow cytometry indicated obvious apoptosis of cells in the experimental group, with arrest in the G1 phase; cell migration ability was also reduced. After pSilencer-siK-Ras2 transfection or the addition of Paclitaxel, EC9706 cells were suppressed to different extents; the suppressive effect was strengthened by combined treatment. The results suggested that RNAi-induced K-Ras gene silencing could enhance chemotherapy sensitivity of esophageal cancer.