• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6433-6438
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• 2013

In hepatocellular cancer (HCC), lack of response to chemotherapy and radiation treatment can be caused by a loss of epigenetic modifications of cancer cells. Methionine adenosyltransferase 1A is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation. Therefore, drugs releasing epigenetic repression have been proposed to reverse this process. We studied the effect of the demethylating reagent 5-aza-2'-deoxycitidine (5-Aza-CdR) on MAT1A gene expression, DNA methylation and S-adenosylmethionine (SAMe) production in the HCC cell line Huh7. We found that MAT1A mRNA and protein expression were activated in Huh7 cells with the treatment of 5-Aza-CdR; the status of promoter hypermethylation was reversed. At the same time, MAT2A mRNA and protein expression was significantly reduced in Huh7 cells treated with 5-Aza-CdR, while SAMe production was significantly induced. However, 5-Aza-CdR showed no effects on MAT2A methylation. Furthermore, 5-Aza-CdR inhibited the growth of Huh7 cells and induced apoptosis and through down-regulation of Bcl-2, up-regulation of Bax and caspase-3. Our observations suggest that 5-Aza-CdR exerts its anti-tumor effects in Huh7 cells through an epigenetic change involving increased expression of the methionine adenosyltransferase 1A gene and induction of S-adenosylmethionine production.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.111-129
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• 1998

In order to research the effect of Sipjundaebotang on the immune respons of CD4+ T cell and CD8+ T cell in rats, author have performed this experimental study. Experimental groups are divided into 5 groups(intact, control, sample I, sample II, sample III). Normal group was intact, control group was administrated normal saline 2cc for 5 days, sample I was administrated low concentration of Sipjundaebotang(100/3100pack/ml) 2cc for 5 days, sample II was administrated middle concentration of Sipjundaebotang(500/3100pack/ml) 2cc for 5 days, sample III was administrated high concentration of Sipjundaebotang(2500/3100pack/ml) 2cc for 5 days. WBC, Lymphocyte, CD4+ T cell in the blood, spleen, axillary node and CD8+ T cell in the blood, spleen and axillary node were determined. The results was as follows: 1. WBC count in blood was significantly decrcased in the control, sample I, II, III groups as compared with the normal group. 2. Lymhocyte count in the blood was significantly decreased in the control, sample I, II groups as compared with the normal group. 3. CD4+ T cell count in the blood was significantly increased dose-dependently in the sample I, II, III groups as compared with the normal group. 4. CD4+ T cell count in the spleen was significantly increased in the sample I, II, III groups as compared with the normal group. 5. CD4+ T cell count in the axillary node was significantly increased in the sample III group as compared with the normal group, however significantly decreased in the sample I, II groups as compared with the normal group. 6. CD8+ T cell count in the blood was significantly increased in the sample III groups as compared with the normal group. 7. CD8+ T cell count in the spleen was significantly increased in the sample I, II, III groups as compared with the normal group. but there was no differences in the sample groups. 8. CD8+ T cell count in the axillary node was decreased in the sample I, II groups as compared with the normal group.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.2
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• pp.85-99
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• 2004

Purpose: This study observed the changes in the telomerase activity, it's developmental regulation, PCNA expression, and their correlation in rat's upper digestive organs during growth and aging. Materials and Methods: Upper digestive organs(buccal mucosa, gingiva, palate, submandibular and parotid glands, and tongue) were aseptically removed from Sprague-Dawley rats of fetal(gestational 20 days), growing(1, 2, 3, 5, and 7 weeks after birth) and adult(12 week old). Samples for telomerase activity were frozen on liquid nitrogen immediately after sacrifice, and stored until the use at $-75^{\circ}C$ in order to measure it. Telomerase activity was measured by a PCR-based telomeric repeat amplication protoco(TRAP) assay and quantitated with Photometric Telo TAGGG Telomerase PCR ELISA plus(Roche Diagnostics GmbH. Mannheim. Germany). PCNA expression were measured immunohistochemistry with anti PCNA Ab-1, Clone PC10(NeoMark. California. USA). Results: 1. Telomerase activities in buccal mucosa, palate and gingiva were the highest in fetus and decreased gradually or rapidly after birth and then diminished, but In salivary gland and tongue were the highest in fetus and also high at 1 week and then decreased rapidly. 2. PCNA expression in buccal mucosa, gingiva, Tongue and salivary gland was the highest in fetus and decreased gradually and then diminished. but only in palate decreased rapidly after birth and then diminished. Conclusion: The highest telomerase activity of embryonic stage decreased rapidly after birth in rat's upper digestive organs. There may be a developmental regulation of telomerase activity, but not a tissue-specific. This telomerase activity seems correlated closely with PCNA expression in rat's upper digestive system.

• Korean Journal of Ichthyology
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• v.28 no.1
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• pp.19-27
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• 2016

The RLG (relative length of gut) is 1.52 (n=12) in the sablefish, Anoplopoma fimbria. The digestive tract has five or six pyloric caeca in the posterior region of stomach. Morphology of mucosal fold is unbranched type in the esophagus and stomach, but branched type in the intestine. The histological structure of digestive tract can be divided into mucosal layer, submucosal layer, muscular layer and serous membrane in the cross section. In the esophagus, mucosal epithelial layer is a simple, and consists of ciliated columnar epithelia and mucous cells. In the stomach, gastric gland of mucosal epithelial layer is a tubular, and is composed of chief cell, parietal cell and mucin secreting cell, which is columnar and contained secretory granules of red and blue colors in the AB-PAS (pH 2.5) reaction. In the intestine, mucosal epithelial layer is a simple, and consists of ciliated columnar epithelia and goblet cells. The submucosal layer is composed mainly of collagen fibers, and well developed in the esophagus. And the muscular layer of digestive tract is divided into longitudinal and circular muscle layer, and well developed in the stomach. The liver is composed of numerous lobular structure and bile canaliculi. Stainability of hepatocyte cytoplasm was eosinophilic, and nucleus and nucleolus showed basophilic in the H-E stain. The pancreatic tissue was scattered in the fatty tissue near the digestive tract, and acinar gland consisting of numerous exocrine cells. And cytoplasmic stainability of exocrine cell was basophilic, and contained numerous zymogen granules of eosinophilic in the H-E stain.

• Molecules and Cells
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• v.42 no.6
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• pp.448-459
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• 2019

The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway is a promising target for gastric cancer (GC) treatment; however the efficacy of PI3K/mTOR dual inhibitors in GC has not yet been maximized. Additionally, the effect of autophagy regulation by PI3K/mTOR dual inhibitors has not been clearly elucidated in GC treatment. We aimed to show that our newly developed PI3K/mTOR dual inhibitor, CMG002, when combined with an autophagy inhibitor, chloroquine (CQ), potently induces effective cancer cell death in Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) cells, where both the PI3K/AKT/mTOR and autophagy pathways play important roles in disease pathogenesis. EBV- and mock-infected AGS and NUGC3 GC cell lines were treated with CMG002 +/- CQ. PI3K/AKT/mTOR signaling pathway mediators, cellular apoptosis and autophagy markers were confirmed by Western blot assay. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. CMG002 effectively blocked the PI3K/AKT/mTOR pathway by markedly decreasing phosphorylation of AKT and its downstream mediator S6. CMG002 induced G0/G1 cell cycle arrest and enhanced apoptotic cell death in AGS and NUGC3 cells, particularly EBV-infected cells compared with mock-infected cells, as confirmed by flow cytometric analyses and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays. The combination of CMG002 plus CQ synergistically increased apoptotic cell death in EBV-infected GC cell lines when compared with CMG002 alone (P < 0.05). Our results suggest that the new PI3K/mTOR dual inhibitor, CMG002, when used in combination with the autophagy inhibitor, CQ, provides enhanced therapeutic efficacy against EBVaGC.

• Animal cells and systems
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• v.6 no.2
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• pp.171-180
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• 2002

Nitric oxide has high affinity for iron, and thus it can cause intracellular iron loss. We tested the idea that intracellular iron can be the primary target of NO toxicity by comparing the signaling mechanisms involved in cell death caused by iron depletion and that caused by NO. Treatment of HL-60 cells with a NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), decreased the intracellular iron level rapidly as that observed with the iron chelator deferoxamine (DFO). Iron chelators such as DFO and mimosine could induce death of human leukemic HL-60 cells by a mechanism requiring activation of p38 kinase, c-Jun N-terminal kinase, caspase-3 and caspase-8. DFO and SNAP also caused release of cytochrome c from mitochondria. Inhibition of p38 kinase by a selective inhibitor, SB203580, abolished the NO and DFO-induced cell death, release of cytochrome c, and activation of caspase-3 and caspase-8, thus indicating that p38 kinase lies upstream in the cell death processes. In a parallel situation, the cells that are sensitive to NO showed similar sensitivity to DFO. Moreover, simultaneous addition of ferric citrate, an iron-containing compound, inhibited the SNAP and DFO-induced activation of caspases and also blocked the NO-mediated cell cycle arrest at $G_1$ phase. Collectively, our data implicate that the NO-induced cell death of tumor cells including HL-60 cells is mediated by depletion of iron and further suggest that activation of p38 kinase lies upstream of cytochrome c release and caspase activation involved in this apoptotic process.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.117-122
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• 2012

Aim: To elucidate the effects of hyperthermic $CO_2$ pneumoperitoneum on human gastric AGS cells. Methods: Based on a newly devised in vitro study model, we evaluated the anti-cancer effects of HT-$CO_2$ ($42-44^{\circ}C$ for 2-4h) on human gastric cancer cells, and also the corresponding mechanisms. Results: HT-$CO_2$ ($42-44^{\circ}C$ for 2-4h) severely inhibited cell proliferation as assessed by Cell Counting Kit-8 assay, while inducing apoptosis in a temperature- and time-dependent manner demonstrated by annexin-V/PI flow cytometry and morphological analysis (Hoechst/PI fluorescence). In addition, it was found that HT-$CO_2$ ($42-44^{\circ}C$ for 2-4h) promoted the up-regulation of Bax by western blotting. Significantly, it could also suppress gastric cancer cell invasion and metastasis by in vitro invasion and motility assay. Conclusion: In conclusion, HT-$CO_2$ had an efficacious cytotoxic effect on gastric cancer cells through Bax-induced mitochondrial apoptotic signaling. Our studies indicate that it may serve as a potential therapy for peritoneal carcinomatosis of gastric cancer. Further investigations in vivo using animal models are now urgently needed.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.89-110
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• 1998

Yookmijihwangtang has been widely used oriental herb prescriptions, which is healing some discuss that come from insufficiency of innate essence and deficiency of kidney Ki. The meaning of healing discusses tonification of insufficient innate essence and insufficient kidney Ki can be regarded as reinforcement of wholely power of keeping homeostasis, that is correlated with immuno-responsibility which protects subject from outer antigen to keep normal vital condition. This study was aimed to investigate correlative effects of Yookmijihwangtang water abstract on the RBC, WBC, blood CD4+ T helper cell count, blood testosterone, blood cAMP and blood cortisol. 40 Sprague-Dawley male rats were divided into 5 groups(Normal, Control, Sample I, Sample II, Sample III), 6 animals in every group. Normal group was not treated anything, control group was administrated normal saline in the same dosage of Sample I. 3 Sample groups were received some of Yookmijihwangtang water abstract at one time per 24 hours during 5 days in different dosage. Sample I(1/310pack/ml), Sample II(1/62pack/ml), Sample III(1/2.4pack/ml). After finishing treatment, all experimental subjects were killed for blood sample on RBC, WBC, blood CD4+ T helper cell count, spleen CD4+ T helper cell count, axillary lymph node CD4+ T helper cell count. blood cAMP, blood testosterone and blood cortisol. The results were as follows; RBC and WBC were increased in all sample groups. Blood CD4+ T helper cell count(CD4+ T cell count in the blood/whole lymphocyte count in the blood ${\times}100%$) was Normal $46.17{\pm}5.88$, Control $44.50{\pm}4.37$, Sample I $53.00{\pm}2.28$, Sample II $53.83{\pm}3.87$, Sample III $52.17{\pm}2.93$. By the 95% Duncan ANOVA all experimental groups(sample I, Sample II, Sample III) showed slight significant difference from Normal and Control. Blood cAMP(nmol/l) were Normal $1.12{\pm}0.17$, Control $1.16{\pm}0.32$, Sample I $0.46{\pm}0.07$, Sample II $0.44{\pm}0.04$, Sample III $0.54{\pm}0.04$. All experimental groups were singificantly different from both Normal and Control groups(p<0.05). Blood cortisol(nl/ml) were Normal $100.00{\pm}2.00$ Control $90.00{\pm}4.00$, Sample I $440.00{\pm}5.00$, Sample II $520.00{\pm}40.00$, Sample III $470.00{\pm}7.00$. Blood cortisol of all experimental groups were significantly increased(p<0.05). The results suggest that Yookmijihwangtang water abstract could be administrated to patients who have some diseases insufficient essence.

• Environmental Analysis Health and Toxicology
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• v.24 no.4
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• pp.341-350
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• 2009

This study involves a relationship between butyltins concentrations and histopathological changes of the digestive gland in the equilateral venus, Gomphina veneriformis exposed to TBTCl of 0.4, 0.6 and 0.8 ${\mu}g/L$ for 36 weeks. In the sediment, total butyltin (${\sum}BT$) concentration was detected ND~7.54 (0.4 ${\mu}g/L$), ND~9.76 (0.6 ${\mu}g/L$), 1.22~13.13 ${\mu}g/L$ (0.8 ${\mu}g/L$), respectively. Especially, TBT level in 0.8 ${\mu}g/L$ group was the highest for 36 weeks. In the soft tissue, total butyltin (${\sum}BT$) concentration of the exposure group was 10.14~12.75 (control), 479.29~1,286.56 (0.4 ${\mu}g/L$), 563.32~2,154.82 (0.6 ${\mu}g/L$) and 1,317.70~2,132.60 ${\mu}g/L$ (0.8 ${\mu}g/L$), respectively. Ratio of TBT to ${\sum}BT$ of the tissue of 0.8 ${\mu}g/L$ kept the lowest level for 36 weeks. The ${\sum}BT$ concentrations of sediment were correlated with ${\sum}BT$ concentrations in the tissue. In the exposure groups, necrosis and atrophy of columnar epithelial cell and collapse of epithelial layer in the digestive tubule. And there was a reduction in stain affinity of basophilic cell. Such histological degenerations was more severe in digestive tubule of 0.8 ${\mu}g/L$ group.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.71-87
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• 1998

Even though appropriate immune response is necessary for the survival of the individual, excessive or insufficient immune Response might cause autoimmune or allergic disease. So the immune response must be controlled to the degree that is beneficial for the well being of the individual. This study was undertaken to know the effects of Gunleetang Gagambang on the immune system of the mouse. Gunleetang Gagambang has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carried out to evaluate the possible therapeutic or antitumoral effects of Gunleetang Gagambang extract against tumor, and to carry out some mechanisms responsible for its effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene(MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(S180 cells). Treatment of the Gunleetang Gagambang on water-extract(dailly 1mg/mouse, i. p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Gunleetang Gagambang decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice(TBM). Gunleetang Gagambang on also significantly suppressed the development of 3LL cell and S180 cell-implanted tumors in occurrence-frequency and their size. and some developed tumors were regressed by the continuous treatment of Gunleetang Gagambang extract into TBM. In vitro, treatment of Gunleetang Gagambang extract had no effect on the growth of some kinds of cell line such as FsaII, A431 strain but significantly inhibited the proliferation of 3LL, S180 cells and augmented the DNA synthesis of mitogen-activated lymphocytes. Gunleetang Gagambang also stimulated the migrative ability of leukocyte, the MIF and IL-2 production of T lymphocytes, but not IL 6 production of B cells. Gunleetang Gagambang administration to mice enhanced NK cells activities. These results demonstrated that Gunleetang Gagambang extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested that effect of Gunleetang Gagambang might be chiefly due to nonspecitie enhancement of NK cell activities and cell-mediated immune responses.