• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.200-205
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• 2005

Purpose: KLF4, a member of the KLF family, is a zinc finger tumor suppressor protein that is critical for gastric epithelial homeostasis. Our aim was to determine whether the altered expression of KLF4 might be associated with gastric cancer development and, if so, to determine to which pathologic parameter it is linked. Materials and Methods: For the construction of the gastric cancer tissue microarray, 84 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of KLF4 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. Results: The KLF4 protein was expressed in cytoplasm and nucleus of superficial and foveolar epithelial cells in the normal gastric mucosa. We found markedly reduced or loss of KLF4 expression in 43 (51.2%) of the 84 gastric cancer tissues. There was no significant correlation between KLF4 expression and pathologic parameters, including histologic type, depth of invasion, lymph node metastasis and peritoneal dissemination. Conclusion: Our findings suggest that altered expression of KLF4 may contribute to abnormal regulation of gastrointestinal epithelial cell growth and differentiation and to the development of Korean gastric cancer, as an early event.

• Journal of Gastric Cancer
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• v.20 no.2
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• pp.139-151
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• 2020

Purpose: Globally, there is a high incidence of gastric cancer (GC). Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is reported to play a vital role in several human malignancies. However, there is limited understanding of the role of LETM1 in GC. This study aims to investigate the effects of LETM1 on proliferation, migration, and invasion of GC cells. Materials and Methods: The expression levels of LETM1 in the normal gastric mucosal epithelial cells (GES-1) and GC cells were analyzed by quantitative real-time polymerase chain reaction and western blotting. CCK-8, wound healing, and Transwell invasion assays were performed to evaluate the effect of LETM1 knockdown or overexpression on the proliferation, migration, and invasion of the GC cells, respectively. Additionally, the effect of LETM1 knockdown or overexpression on GC cell apoptosis was determined by flow cytometry. Furthermore, the effect of LETM1 knockdown or overexpression on the expression levels of PI3K/Akt signaling pathway-related proteins was evaluated by western blotting. Results: The GC cells exhibited markedly higher mRNA and protein expression levels of LETM1 than the GES-1 cells. Additionally, the knockdown of LETM1 remarkably suppressed the GC cell proliferation, migration, and invasion, and promoted the apoptosis of GC cells, which were reversed upon LETM1 overexpression. Furthermore, the western blotting analysis indicated that LETM1 facilitates GC progression via the PI3K/Akt signaling pathway. Conclusions: LETM1 acts as an oncogenic gene to promote GC cell proliferation, migration, and invasion via the PI3K/Akt signaling pathway. Therefore, LETM1 may be a potential target for GC diagnosis and treatment.

• Applied Microscopy
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• v.20 no.1
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• pp.105-119
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• 1990

In order to know the morphological characteristics and changes according to the developmental stage, the comparative observations have been studied by light and electron microscope on the midgut(gastric caecum, stomach) of the grasshopper(Oxya sinuosa Mistshenko). The results obtained are summarized as follow : In light microscopic level, the cuboidal shaped cells of the gastric caecum in the 5th instar nymph are differentiated the columnar epithelium in the adult. A number of pigment granules are appeared in the gastric caecum of the 5th instar nymph, however the pigment granules were absent in the adult. Indistinct or undifferentiated folds of the epithelial layer were appeared in the 5th instar nymph, whereas the well-developed folds were appeared the gastric caecum in the adult. The well-developed muscular layers are seen in the 5th instar numph, however in the adult the muscular layers are appeared thin or a few layers. In electron microscopic level, in the midgut epithelium, a number of well-developed rER, a few lipid droplets, multi vesicular bodies, small vesicles and glycogen granules were found. Two types of the pigment granules in the gastric caecum of the 5th instar nymph were appeared, whereas the whorl-membrane, a few secretory granules and one type of the gastro-entero-endocrine cell were found in the adult midgut. The light and dark cells could be distinguished in the stomach epithelim of the 5th instar nymph.

• Archives of Pharmacal Research
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• v.22 no.1
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• pp.1-8
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• 1999

Transforming growth factor-$\beta$ (TGF-$\beta$) is the prototypical multifunctional cytokine, participating in the regulation of vital cellular activities such as proliferation and differentiations as well as a number of basic physiological functions. The effects of TGF-$\beta$ are critically dependent on the expression and distribution of a family of TGF-$\beta$ receptors, the TGF-$\beta$ types I, II, and III. It is now known that a wide variety of human pathology can be caused by aberrant expression and function of these receptors. the coding sequence of the type II receptor (RII) appears to render it uniquely susceptible to DNA replication errors in the course of normal cell division. By virtue of its key role in the regulation of cell proliferation, TGF-$\beta$ RII should be considered as a tumor suppressor gene. High levels of mutation in the TGF-$\beta$ RII gene have been observed in a wide range of primarily epithelial malignancies, including colon and gastric cancer. It appears likely that mutation of the TGF-$\beta$ RII gene may be a very critical step in the pathway of carcinogenesis.

• International Journal of Oral Biology
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• v.31 no.2
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• pp.27-32
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• 2006

Expression of invasion/metastasis suppressor, E-cadherin, is reduced in many types of human carcinomas. Although somatic and germline mutations in the CDH1, which encodes the human E-cadherin, have frequently been reported in cases with diffuse gastric and lobular breast cancers, irreversible genetic inactivations are rare in other human carcinomas. Recently, it has been well documented that some genes in human cancers may be inactivated by altered CpG methylation. Herein, we determined the expression and methylation status of E-cadherin in oral squamous cell carcinoma(SCC) by immunohistochemistry and methylation-specific PCR. The expression of E-cadherin was significantly higher in the well-differentiated oral SCCs than the moderately or poorly differentiated ones. None of eight tested benign epithelial hyperplasias showed aberrant methylation, whereas five of 12 oral squamous cell carcinomas showed aberrant methylation. When we compared E-cadherin expression with methylation status, oral SCCs with normal methylation showed a higher expression of E-cadherin than those with methylation. These findings suggest that aberrant CpG methylation of CDH1 promoter region is closely associated with transcriptional inactivation and might be involved in tumor progression of the oral mucosa.

• Journal of Digestive Cancer Research
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• v.5 no.2
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• pp.105-112
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• 2017

Background: The expression of miRNAs in response to Helicobacter pylori infection has not been well explored. The aims of this study were to evaluate the H. pylori associated miRNAs in the gastric epithelial cells. Methods: We investigated gastric epithelial cell-line (HS3C) exposed H. pylori over 3 months and AGS cell-line (AGS) exposed H. pylori for 6 hour. After the extraction of miRNA from these cell-lines, microarray and real time PCR were performed to confirm the alteration of expression. Results: All 12 miRNAs chosen for real-time PCR are based on the result of microarray and their potential functions related to H. pylori infection. miR-21, miR-221, miR-222 were upregulated in the H. pylori infected AGS cell for 6 hours and HS3C cells. miR-99b, miR-200b, miR-203b and miR-373 were downregulated in the H. pylori infected AGS cell for 6 hours and HS3C cells. miR-23a, miR-23b, miR-125b, miR-141 and miR-155 were upregulated in HS3C cell line but not in H. pylori infected AGS cell for 6 hours. Conclusion: miR-21, miR-99b, miR-125b, miR-200b, miR-203b, miR-221, miR-222, and miR-373 are supposed to be related with oncogenesis of H. pylori infection. Further studies are needed for the evaluation of the function of these confirmed miRNAs.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5815-5818
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• 2014

For an exact comparison of mRNA transcription in different samples or tissues with real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), it is crucial to select a suitable internal reference gene. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB) have been frequently considered as house-keeping genes to normalize for changes in specific gene expression. However, it has been reported that these genes are unsuitable references in some cases, because their transcription is significantly variable under particular experimental conditions and among tissues. The present study was aimed to investigate which reference genes are most suitable for the study of gastric cancer tissues using qRT-PCR. 50 pairs of gastric cancer and corresponding peritumoral tissues were obtained from patients with gastric cancer. Absolute qRT-PCR was employed to detect the expression of GAPDH, ACTB, RPII and 18sRNA in the gastric cancer samples. Comparing gastric cancer with corresponding peritumoral tissues, GAPDH, ACTB and RPII were obviously upregulated 6.49, 5.0 and 3.68 fold, respectively. Yet 18sRNA had no obvious expression change in gastric cancer tissues and the corresponding peritumoral tissues. The expression of GAPDH, ${\beta}$-actin, RPII and 18sRNA showed no obvious changes in normal gastric epithelial cells compared with gastric cancer cell lines. The carcinoembryonic antigen (CEA), a widely used clinical tumor marker, was used as a validation gene. Only when 18sRNA was used as the normalizing gene was CEA obviously elevated in gastric cancer tissues compared with peritumoral tissues. Our data show that 18sRNA is stably expressed in gastric cancer samples and corresponding peritumoral tissues. These observations confirm that there is no universal reference gene and underline the importance of specific optimization of potential reference genes for any experimental condition.

• Journal of Microbiology and Biotechnology
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• v.13 no.5
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• pp.666-672
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• 2003

Vacuolar degeneration of the gastric epithelial cells is a characteristic feature of the derangement of mucosa where Helicobacter pylori colonizes, and H. pylori vacuolating cytotoxin (VacA) has been suggested to playa key role in it. To elucidate the VacA-involved degenerative mechanism, VacA was purified, and its impact on degeneration of HeLa cells was determined. In the presence of ammonium chloride, cell vacuolation by VacA was dose-and time-dependent, however, no detectable degeneration of the cells was observed with the VacA concentration tested. A further increase of vacuolation was shown in cells pre-treated with diethyl pyrocarbonate (DEPC) , and this resulted in a change of the cell morphology to become spherical. Similar phenomena were also observed when HeLa cells were co-cultivated with intact H. pylori cells. It was remarkable to note that the degree of growth inhibition was proportional to the increase in vacuole formation, suggesting that the vacuolation rate would be critical for cell degeneration. Surprisingly, although VacA was itself inhibited by DEPC, its uptake was markedly increased by this agent, similar to that found in cells with Nabutyrate. These data indicate that the cell's tolerance of VacA transport may be critical for vacuolar degeneration and may be changeable during H. pylori inhabitation.

• Microbiology and Biotechnology Letters
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• v.22 no.5
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• pp.477-484
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• 1994

Using a methylotrophic yeast Hansenula polymorpha, a heterologous gene expression and secretion system was developed for the production of hEGF(human Epidermal Growth Factor) which has been shown to promote epithelial cell proliferation and to inhibit gastric acid secretion. The hEGF gene was chemically synthesized according to the preferred codon usage in H. polymor- pha and expressed under the control of the strong and inducible methanol oxidase(MOX) promoter. The mating factor $\alpha$ pre-pro leader sequence of Saccharomyces cerevisiae was employed for hEGF to be secreted into the extracellular medium. This expression cassette was stably integrated into the host chromosomal DNA. Mature hEGF was efficiently expressed and secreted into the extracel- lular medium. About 24 mg/l of hEGF was detected in the cuture supernatant of a transformant with pA-EGF3 under the suboptimal culture conditions.

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.177-186
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• 1994

Bioadhesive microcapsules of cephalexin, using Eudragit RS/RL coated with polycarbophil or carbopol, were evaluated biopharmaceutically. The GI transit of microcapsules in rats was studied. Bioadhesive microcapsules coated with polycarbophil or carbopol were shown to have substantially longer GI transit time than Eudragit RS/RL microcapsule. The delay in transit time was due to bioadhesion of the polymer to the mucin-epithelial cell surface which was clearly observable on animal autopsy. Plasma drug levels in rabbits showed that bioadhesive microcapsules resulted in a longer duration of action and greater bioavailability than other microcapsule or drug powder. Thus, the principle of bioadhesion can significantly improve therapy, due to a reduced rate of gastric emptying, an increase in contact time, and the intimacy of contact of the drug with the absorbing membrane.