• Food Science and Biotechnology
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• v.15 no.5
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• pp.799-804
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• 2006

Ingestion of green tea has been shown to decrease prostaglandin $E_2$ levels in human colorectum, suggesting that tea constituents modulate arachidonic acid metabolism. In the present study, we investigated the effects of four purified green tea catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG), and (-)-epicatechin-3-gallate (ECG), on the catalytic activity of cytosolic phospholipase $A_2$ ($cPLA_2$) and release of arachidonic acid and its metabolites from intact cells. At $50\;{\mu}M$, EGCG and ECG inhibited $cPLA_2$ activity by 19 and 37%, respectively, whereas EC and EGC were less effective. The inhibitory effects of these catechins on arachidonic acid metabolism in intact cells were much more pronounced. At $10\;{\mu}M$, EGCG and ECG inhibited the release of arachidonic acid and its metabolites by 50-70% in human colon adenocarcinoma cells (HT-29) and human esophageal squamous carcinoma cells (KYSE-190 and 450). EGCG and ECG also inhibited arachidonic acid release induced by A23187, a calcium ionophore, in both HT-29 and KYSE-450 cell lines by 30-50%. The inhibitory effects of green tea catechins on $cPLA_2$ and arachidonic acid release may provide a possible mechanism for the prevention of human gastrointestinal inflammation and cancers.

• Korean Journal of Food Science and Technology
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• v.23 no.3
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• pp.306-310
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• 1991

A simplified mathematical model to estimate changes in total acidity of Chinese cabbage kimchi during fermentation was developed as a function of temperature and salt concentration. Assuming that tolerable acceptability reached at 0.75% total acidity, the shelf-life of kimchi was predicted by the model. The predicted value was in good agreement with the actual shelf-life measured by organoleptic tests.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.546-551
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• 2001

We have previously shown that, in circular muscle cells of the lower esophageal sphincter (LES) isolated by enzymatic digestion, contraction in response to maximally effective doses of acetylcholine (ACh) or Inositol Triphosphate ($IP_3$) depends on the release of $Ca^{2+}$ from intracellular stores and activation of a $Ca6{2+}$-calmodulin (CaM)-dependent pathway. On the contrary, maintenance of LES tone, and response to low doses of ACh or $IP_3$ depend on a protein kinase C (PKC) mediated pathway. In the present investigation, we have examined requirements for $Ca6{2+}$ regulation of the interaction between CaM- and PKC-dependent pathways in LES contraction. Thapsigargin (TG) treatment for 30 min dose dependently reduced ACh-induced contraction of permeable LES cells in free $Ca6{2+}$ medium. ACh-induced contraction following the low level of reduction of $Ca6{2+}$ stores by a low dose of TG ($10^{-9}{\;}M$) was blocked by the CaM antagonist, CCS9343B but not by the PKC antagonists chelerythrine or H7, indicating that the contraction is CaM-dependent. After maximal reduction in intracellular $Ca{2+}$ from $Ca6{2+}$stores by TG ($10^{-6}{\;}M$), ACh-induced contraction was blocked by chelerythrine or H7, but not by CCS9343B, indicating that it is PKC-dependent. In normal $Ca^{2+}$medium, the contraction by ACh after TG ($10^{-9}{\;}M$) treatment was also CaM-dependent, whereas the contraction by ACh after TG ($10^{-9}{\;}M$) treatment was PKC-dependent. We examined whether PKC activation was inhibited by activated CaM. CCS 7343B Inhibited the CaM-induced contraction, but did not inhibit the DAC-induced contraction. CaM inhibited the DAC-induced contraction in the presence of CCS 9343B. This inhibition by CaM was $Ca{2+}$dependent. These data are consistent with the view that the switch from a PKC-dependent pathway to a CaM dependent pathway can occur and can be regulated by cytosolic $Ca{2+}$ in the LES.

• Molecules and Cells
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• v.37 no.12
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• pp.873-880
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• 2014

In our previous study, miRNA-183, a miRNA in the miR-96-182-183 cluster, was significantly over-expressed in esophageal squamous cell carcinoma (ESCC). In the present study, we explored the oncogenic roles of miR-183 in ESCC by gain and loss of function analysis in an esophageal cancer cell line (EC9706). Genome-wide mRNA micro-array was applied to determine the genes that were regulated directly or indirectly by miR-183. 3'UTR luciferase reporter assay, RT-PCR, and Western blot were conducted to verify the target gene of miR-183. Cell culture results showed that miR-183 inhibited apoptosis (p < 0.05), enhanced cell proliferation (p < 0.05), and accelerated G1/S transition (p < 0.05). Moreover, the inhibitory effect of miR-183 on apoptosis was rescued when miR-183 was suppressed via miR-183 inhibitor (p < 0.05). Western blot analysis showed that the expression of programmed cell death 4 (PDCD4), which was predicted as the target gene of miR-183 by microarray profiling and bioinformatics predictions, decreased when miR-183 was over-expressed. The 3'UTR luciferase reporter assay confirmed that miR-183 directly regulated PDCD4 by binding to sequences in the 3'UTR of PDCD4. Pearson correlation analysis further confirmed the significant negative correlation between miR-183 and PDCD4 in both cell lines and in ESCC patients. Our data suggest that miR-183 might play an oncogenic role in ESCC by regulating PDCD4 expression.

• The Korean Journal of Nuclear Medicine
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• v.34 no.1
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• pp.62-73
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• 2000

Purpose: Esophageal cancer patients have a difficulty in the intake of meals through the blocked esophageal lumen, which is caused by an ingrowth of cancer cells and largely influences on the prognosis. It is reported that esophageal cancer has a very low survival rate due to the lack of nourishment and immunity as the result of this. In this study a new radioactive stent, which prevents tumor ingrowth and restenosis by additional radiation treatment, has been developed. Materials and Methods: Using ${\ulcorner}HANARO{\lrcorner}$ research reactor, the radioactive stent assembly ($^{166}Ho$-SA) was prepared by covering the metallic stent with a radioactive sleeve by means of a post-irradiation and pre-irradiation methods. Results: Scanning electron microscopy and autoradiography exhibited that the distribution of $^{165/166}Ho\;(NO_3)$ compounds in polyurethane matrix was homogeneous. A geometrical model of the esophagus considering its structural properties, was developed for the computer simulation of energy deposition to the esophageal wall. The dose distributions of $^{166}Ho$-stent were calculated by means of the EGS4 code system. The sources are considered to be distributed uniformly on the surface in the form of a cylinder with a diameter of 20 mm and length of 40 mm. As an animal experiment, when radioactive stent developed in this study was inserted into the esophagus of a Mongrel dog, tissue destruction and widening of the esophageal lumen were observed. Conclusion: We have developed a new radioactive stent comprising of a radioactive tubular sleeve covering the metallic stent, which emits homogeneous radiation. If it is inserted into the blocked or narrowed lumen, it can lead to local destruction of the tumor due to irradiation effect with dilatation resulting from self-expansion of the metallic property. Accordingly, it is expected that restenosis esophageal lumen by the continuous ingrowth and infiltration of cancer after insertion of our radioactive stent will be decreased remarkably.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• The Korean Journal of Cytopathology
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• v.18 no.2
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• pp.133-142
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• 2007

Cytologic diagnosis of the metastatic tumors to the thyroid is important in the management of the patients. There have been rare reports analyzing fine-needle aspiration (FNA) cytology of metastatic tumors to the thyroid. This study examines comprehensive cytologic findings of metastatic tumors to the thyroid with radiologic findings. The FNA cytology slides obtained from 12 cases with metastatic tumors of the thyroid; lung cancer (n=5), tongue and tonsil cancer (n=3), esophageal cancer (n=2), and breast cancer (n=2) were reviewed. Radiological study showed single mass with heterogeneous texture or multiple masses without calcification. Metastatic tumor was easily considered in a differential diagnosis of FNA cytology because they had peculiar cytological features which were not seen in primary thyroid tumor. The smear background varied from predominantly necrotic, bloody, and inflammatory to colloid. The aspirates exhibited a mixture of benign follicular cells and malignant cells in 6 cases. The characteristic cytoplasmic features of the tumor cells, such as keratin, mucin and melanin, were found in 9 cases. Although some cases mimic primary thyroid neoplasm, a careful examination of the cytological characteristics may help cytopathologists to recognize a metastatic tumor in the thyroid by FNA, and may help the clinicians to establish a proper treatment plan.

• Journal of Pharmacopuncture
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• v.17 no.1
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• pp.59-69
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• 2014

Objectives: In homeopathy, it is claimed that more homeopathically-diluted potencies render more protective/curative effects against any disease condition. Potentized forms of Condurango are used successfully to treat digestive problems, as well as esophageal and stomach cancers. However, the comparative efficacies of Condurango 6C and 30C, one diluted below and one above Avogadro's limit (lacking original drug molecule), respectively, have not been critically analyzed for their cell-killing (apoptosis) efficacy against lung cancer cells in vitro, and signalling cascades have not been studied. Hence, the present study was undertaken. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted on H460-non-small-cell lung cancer (NSCLC) cells by using a succussed ethyl alcohol vehicle (placebo) as a control. Studies on cellular morphology, cell cycle regulation, generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential (MMP), and DNA-damage were made, and expressions of related signaling markers were studied. The observations were done in a "blinded" manner. Results: Both Condurango 6C and 30C induced apoptosis via cell cycle arrest at subG0/G1 and altered expressions of certain apoptotic markers significantly in H460 cells. The drugs induced oxidative stress through ROS elevation and MMP depolarization at 18-24 hours. These events presumably activated a caspase-3-mediated signalling cascade, as evidenced by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot and immunofluorescence studies at a late phase (48 hours) in which cells were pushed towards apoptosis. Conclusion: Condurango 30C had greater apoptotic effect than Condurango 6C as claimed in the homeopathic doctrine.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.473-477
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• 2012

Introduction: The esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances, and a current challenge is the development of effective therapeutic agents. Our present work addressed the effect of HIF-$1{\alpha}$ siRNA alone or in combination with cisplatin on the growth of ESCC in nude mice. Materials and Methods: Xenografts were established by inoculating ESCC TE-1 cells in nude mice, and transplanted tumors were treated with HIF-$1{\alpha}$ siRNA, cisplatin alone or together. Growth was assessed by measuring tumor volume. HIF-$1{\alpha}$ mRNA and protein expression were detected using RT-PCR and immunohistochemistry, respectively. Apoptosis of ESCC TE-1 cells was analyzed by flow cytometry. Results: In our nude mice model, HIF-$1{\alpha}$ siRNA effectively inhibited the growth of transplanted ESCC, downregulating HIF-$1{\alpha}$ mRNA and protein expression, and inducing ESCC TE-1 cell apoptosis. Notably when combinated with cisplatin, HIF-$1{\alpha}$ siRNA showed synergistic interaction in suppressing tumor growth. Furthermore, the proportion of apoptotic cells in HIF-$1{\alpha}$ siRNA plus cisplatin group was significantly higher than that in cisplatin or HIF-$1{\alpha}$ siRNA-treated groups (P<0.05). Conclusions: Down-regulated HIF-$1{\alpha}$ expression induced by siRNA could effectively suppress the growth of transplanted ESCC $in$ $vivo$. HIF-$1{\alpha}$ siRNA could enhance the cytotoxicity of cisplatin, which suggests that a combination of these two agents may have potential for therapy of advanced ESCC.