• 생명과학회지
• /
• 제11권6호
• /
• pp.595-602
• /
• 2001

The prelectin histochemical methods had been applied to study mucosubstances properties of esophageal mucous cells in four teleostean species, i, e.. sebastes schlegli, Halichoeres poecilopterus, Bryzoichtys lysimus and Takifugu pardalis. The following methods were used: periodic acid Scheff"s(PAS) reaction, alcian blue(AD) pH 2.5, AB pH 1.0, AB pH 2.5-PAS, aldehyde fuchsin (AF) pH 1.7-AB pH 2.5 and high iron diamine (HID)-AD pH 2.5 stainings. The number size and shape of esophasgeal mucous cells studied depend on the fish species. Esophageal mucous cells of Sebastes schlegli and Halichoeres poecilopterus were mixed with large, medium sized and small mucous cells, but these cells of the species were mixed with medium sized and small mucous cells. The large esophageal with moderate to considerable amount of acid mucin. Most of the large mucous cells in these species contained neutral mucin and strongly sulfomucin, whereas a few mucous cells contained neutral mucin, strongly sulfomucin, and sialomucin. Medium sized and small mucous cells of these species contained considerable to large amount of neutral mucin, and small to considerable amount of acid mucin, Most of the medium sized and small mucous cells contained neutral mucin and sialomucin, but a few mucous cells contained neutral mucin and strongly sulfomucin or neutral combined with strongly sulfomucin and sialomucin. Most of the esophageal mucous cells pf Bryzoichthys lysimus contained small amount of neutral mucin, while on the other hand a feww mucous cells contained small amount of neutral mucin and minimal amount of sialomucin. But the esophageal mucous cells of Takifugu pardalis contained considerable amount of neutral mucin only.

• The Korean Journal of Physiology and Pharmacology
• /
• 제27권5호
• /
• pp.493-511
• /
• 2023

Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells. Silencing YAP under UA plus DIM conditions significantly increased the activation of the tumor suppressor PTEN in esophageal cancer cells, while decreasing p-Akt activation, indicating that the Akt signaling pathway could be down-regulated in esophageal cancer cells by targeting PTEN. Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.

• 생명과학회지
• /
• 제14권3호
• /
• pp.417-424
• /
• 2004

경골어류인 조피볼락, 용치놀래기, 송곳니베도라치 및 졸복 식도 점액세포의 복합당질 성상을 biotinylated lectin인 DBA, SBA, PNA, BSL-1, RCA-1, sWGA, UEA-1, LCA 및 Con A로 연구하였다. 조피볼락과 용치놀래기는 큰ㆍ중간 및 작은 점액세포가 섞여 있었고, 송곳니베도라치와 졸복은 중간 및 작은 점액세포들이 섞여 있었다. 식도 점액세포들의 lectin 결합양상도 어종에 따라 차이가 있었으며 조피볼락은 DBA, SBA, BSL-1, RCA-1 및 sWGA에, 용치 놀래기는 DBA, SBA, PNA 및 sWGA에, 송곳니베도라치는 SBA 및 sWGA에 각각 반응을 하였으며 졸복은 DBA, LCA 및 Con A를 제외한 모든 lectin에 반응하였다. 조피볼락의 모든 점액세포에는 DBA, SBA 및 sWGA가, 작은 점액세포에는 이 외에 BSL-1이 반응하였다. 용치놀래기의 큰 점액세포에서는 PNA가, 중간 점액세포에는 DBA, SBA 및 sWGA가, 작은 점액세포에는 DBA와 SBA가 반응하였다. 송곳니베도라치의 중간 점액세포에는 sWGA가, 작은 점액세포에는 SBA와 sWGA가 반응하였으며 졸복은 모든 점액세포에 SBA, PNA 및 RCA-1가, 중간 점액세포에는 이 외에 sWGA와 UEA-1이 반응하였다. 특히 조피볼락의 점액세포에서 DBA와 SBA의 양이 많고, 용치놀래기에서는 큰 점액세포에서 PNA 양이, 중간 및 작은 점액세포에서 SBA양이 많았으며, 졸복의 경우 중간 점액세포에서 SBA, PNA, sWGA 및 UEA-1의 양이, 작은 점액세포에서 RCA-1의 양이 많았다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권8호
• /
• pp.4891-4896
• /
• 2013

Objective: To separate/enrich tumor stem-like cells from the human esophageal carcinoma cell line OE-19 by using serum-free suspension culture and to identify their biological characteristics and radiation resistance. Methods: OE-19 cells were cultivated using adherent and suspension culture methods. The tumor stem-like phenotype of CD44 expression was detected using flow cytometry. We examined growth characteristics, cloning capacity in soft agar, and radiation resistance of 2 groups of cells. Results: Suspended cells in serum-free medium formed spheres that were enriched for CD44 expression. CD44 was expressed in 62.5% of suspended cells, but only in 11.7% of adherent cells. The suspended cells had greater capacity for proliferation and colony formation in soft agar than the adherent cells. When the suspended and adherent cells were irradiated at 5 Gy, 10 Gy, or 15 Gy, the proportion of CD44+ suspended cells strongly and weakly positive for CD44 was 77.8%, 66.5%, 57.5%; and 21.7%, 31.6%, 41.4%, respectively. In contrast, the proportion of CD44+ adherent cells strongly positive for CD44 was 18.9%, 14.%, and 9.95%, respectively. When the irradiation dose was increased to 30 Gy, the survival of the suspended and adherent cells was significantly reduced, and viable CD44+ cells were not detected. Conclusion: Suspended cell spheres generated from OE-19 esophageal carcinoma cells in serum-free stem medium are enriched in tumor stem-like cells. CD44 may be a marker for these cells.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권20호
• /
• 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.

• Molecules and Cells
• /
• 제38권7호
• /
• pp.616-623
• /
• 2015

P2 receptors are membrane-bound receptors for extracellular nucleotides such as ATP and UTP. P2 receptors have been classified as ligand-gated ion channels or P2X receptors and G protein-coupled P2Y receptors. Recently, purinergic signaling has begun to attract attention as a potential therapeutic target for a variety of diseases especially associated with gastroenterology. This study determined the ATP and UTP-induced receptor signaling mechanism in feline esophageal contraction. Contraction of dispersed feline esophageal smooth muscle cells was measured by scanning micrometry. Phosphorylation of $MLC_{20}$ was determined by western blot analysis. ATP and UTP elicited maximum esophageal contraction at 30 s and $10{\mu}M$ concentration. Contraction of dispersed cells treated with $10{\mu}M$ ATP was inhibited by nifedipine. However, contraction induced by $0.1{\mu}M$ ATP, $0.1{\mu}M$ UTP and $10{\mu}M$ UTP was decreased by U73122, chelerythrine, ML-9, PTX and $GDP{\beta}S$. Contraction induced by $0.1{\mu}M$ ATP and UTP was inhibited by $G{\alpha}i_3$ or $G{\alpha}q$ antibodies and by $PLC{\beta}_1$ or $PLC{\beta}_3$ antibodies. Phosphorylated $MLC_{20}$ was increased by ATP and UTP treatment. In conclusion, esophageal contraction induced by ATP and UTP was preferentially mediated by P2Y receptors coupled to $G{\alpha}i_3$ and $G{\alpha}q$ proteins, which activate $PLC{\beta}_1$ and $PLC{\beta}_3$. Subsequently, increased intracellular $Ca^{2+}$ and activated PKC triggered stimulation of MLC kinase and inhibition of MLC phosphatase. Finally, increased $pMLC_{20}$ generated esophageal contraction.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권12호
• /
• pp.7375-7379
• /
• 2013

The main aim of this study was to investigate the roles of GST-${\pi}$ and $pol{\beta}$ genes in the chemoresistance of esophageal carcinoma cells. Eukaryotic expression vectors containing each gene were constructed and transfected into EC9706 cells, and the biological effects of the two genes assessed based on a resistance index. We additionally investigated the in vitro and in vivo anti-resistance effects of GST-${\pi}$ and $pol{\beta}$ genes using recombinant lentiviruses carrying siRNAs against the two genes. Our results showed that upregulation of GST-${\pi}$ and $pol{\beta}$ genes suppresses chemosensitivity of esophageal carcinoma cells to cisplatin, while downregulation of these two genes with RNAi technology reverses this chemoresistance. Multi-site injection of recombinant lentivirus targeting the GST-${\pi}$ gene into transplanted cDDP tumors effectively reversed their chemoresistant phenotype. However, the same treatment against the $pol{\beta}$ gene did not lead to significant efficacy against chemoresistance.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권5호
• /
• pp.2207-2212
• /
• 2012

Overexpression of DNA methyltransferase 1 (DNMT1) has been detected in many cancers. Tobacco exposure is known to induce genetic and epigenetic changes in the pathogenesis of malignancy. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen present in tobacco smoke; however the detailed molecular mechanism of how NNK induces esophageal carcinogenesis is still unclear. We found that DNMT1 was overexpressed in ESCC tissues compared with paired non-cancerous tissues, the overexpression being correlated with smoking status and low expression of $RAR{\beta}$. The latter could be upregulated by NNK treatment in Het-1A cells, and the increased DNMT1 expression level reflected promoter hypermethylation and downregulation of retinoic acid receptor ${\beta}$($RAR{\beta}$). RNA interference mediated knockdown of DNMT1 resulted in promoter demethylation and upregulation of $RAR{\beta}$ in KYSE30 and TE-1 cells. 3-(4,5-Dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis demonstrated that NNK treatment in Het-1A cells could enhance cell proliferation and inhibit cell apoptosis in a dose-dependent manner. In conclusion, DNMT1 overexpression is correlated with smoking status and low expression of $RAR{\beta}$ in esophageal SCC patients. NNK could induce $RAR{\beta}$ promoter hypermethylation through upregulation of DNMT1 in esophageal squamous epithelial cells, finally leading to enhancement of cell proliferation and inhibition of apoptosis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권3호
• /
• pp.997-1000
• /
• 2015

Esophageal cancer represents the fourth most common gastrointestinal cancer and generally confers a poor prognosis. Prostaglandin-producing cyclo-oxygenase has been implicated in the pathogenesis of esophageal cancer growth. Here we report that prostaglandin dehydrogenase, the major enzyme responsible for prostaglandin degradation, is significantly reduced in expression in esophageal cancer in comparison to normal esophageal tissue. Reconstitution of PGDH expression in esophageal cancer cells suppresses cancer cell growth, at least in part through preventing cell proliferation and promoting cell apoptosis. The tumor suppressive role of PGDH applies equally to both squamous cell carcinoma and adenocarcinoma, which enriches our understanding of the pathogenesis of esophageal cancer and may provide an important therapeutic target.

• Journal of Life Science
• /
• 제10권2호
• /
• pp.1-8
• /
• 2000

This experiment was performed to study the structure of esophageal mucousa and the histochemical properties of glycosaminoglycans of esophageal mucous cells in four teleostean species, i.e., Agramus agramus, Inimicus japonicus, Epinephelus chlorostigma and Helicolenus dactylopterus. To observe the structure of eosphageal mucosa, hematoxylin-eosin(H-E) staining was used. The glycosaminoglycans was stained with PAS(periodic acid schiff), alcain blue(AB) pH 2.5, AB pH 1.0, aldehyde fuchsin(AF) pH 1.7, AF pH 1.0, AB pH 2.5-PAS, AB pH 1.0-PAS and AF pH 1.7-alcian blue pH 2.5. As for the amount and histochemical composition of glycosaminglycans in Agramus agramus, most of mucous secreting columnar cell and mucous cells contain large and moderate amount of neutral glycosaminoglycans. A few of mucous cells having small amount of neutral glycosamino-glycans and minimal amount of sulfated glycosamino-glycans. In Inimicus japonicus, the esophageal mucous cells were composed of most of medium sized and large mucous cells with moderate amount of neutral glycosaminoglycanonly only, a few of medium sized and large mucous cells and most of small mucous cells with considerable amount of neutral glycosaminoglycans and minimal to small amount of nonsulfated glycosaminoglycans, and a feq of small mucous cells with small amount of neutral glycosaminoglycans and minimal amount of sulfated glycosaminoglycans. In Epinephelus chlorostigma, most of medium sized and large mucous cells were mixed small amount of neutral glycosaminoglycans with sulfated glycosaminoglycans, a few of which were contained with moderate or considerable amount of neutral glycosaminoglycans with sulfated glycosaminoglycans, while most of small mucous cells containing considerable amount of neutral glycosaminoglycans and small to moderate or considerable to minimal amount of nonsulfated glycosaminoglycans(sialomucin) a few of which containing a mixture of considerable amount of neutral glycosaminoglycans and considerable amount of nonsulfated glycosaminoglycans(sialomucin)only. In Helicolenus dactylopterus, most of medium sized and large mucous cells, mixing with moderate to considerable amount of neutral glycosaminoglycans and small to moderate amount of sulfated glycosaminoglycans, while most of small mucous cells with considerable amount of nonsulfated glycosaminoglycans (sialomucin), a few of which having a mixture of considerable amount of neutral glycosaminoglycans and considerable or small amount of nonsulfated glycosaminoglycans(sialomucin).