• Biomolecules & Therapeutics
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• 제18권4호
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• pp.402-410
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• 2010

Although the overproduction of prostaglandin $E_2$ ($PGE_2$) in intestinal epithelial cells has been considered to be highly correlated with the colorectal carcinogenesis, the precise mechanism of action remains poorly elucidated. Accumulating evidence suggests that the PGE receptor (EP)-mediated signal transduction pathway might play an important role in this process. In the present study, we investigated the mechanism of action underlying $PGE_2$-mediated cell proliferation and the effect of resveratrol on the proliferation of human colon cancer cells in terms of the modulating $PGE_2$-mediated signaling pathway. $PGE_2$ stimulated the proliferation of several human colon cancer cells and activated growth-stimulatory signal transduction, including Akt and ERK. $PGE_2$ also increased the phosphorylation of GSK-$3{\beta}$, the translocation of ${\beta}$-catenin into the nucleus, and the expressions of c-myc and cyclin D1. Resveratrol, a cancer chemopreventive phytochemical, however, inhibited $PGE_2$-induced growth stimulation and also suppressed $PGE_2$-mediated signal transduction, as well as ${\beta}$-catenin/T cell factor-mediated transcription in human colon cancer cells. These findings present an additional mechanism through which resveratrol affects the regulation of human colon cancer cell growth.

• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.167-172
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• 2000

The purpose of this study is to develop a transurethral liquid suppository containing prostaglandin $E_1\;(PGE_1)-loaded$ microemulsion, which undergoes a phase transition to gels at body temperature. The effects of oils, ethanol as solvent and HCl as pH-controlling agent on the physicochemical properties of liquid suppositories composed of poloxamer P 407, P 188 and carbopol was investigated. The stability of $PGE_1$ and release of $PGE_1$ from liquid suppository were evaluated. Oils such as Neobee and soybean oil significantly decreased the gelation temperature but increased the gel strength of liquid suppository due to their strongly binding with the components of liquid suppository base. However, ethanol slightly did the opposite. The pH of liquid suppositories hardly affected the gelation temperature and gel strength due to addition of very small HCl (0.005-0.01%). A liquid suppository [$PGE_1/P$ 407/P 188/carbopol/Neobee/ethanol/HCl (0.2/14/14/0.4/7/2/0.005%)], which had the gelation temperature $(34.2{\pm}0.6^{\circ}C)$ and gel strength $(31.35{\pm}4.37\;sec)$ suitable for liquid suppository system, was easily administered and not leak out from the body. About 60% of $PGE_1$ was released out within 2 h from this formulation. It was shown that the release of $PGE_1$ was proportional to the square root of time, indicating that $PGE_1$ might be released from the suppository by Fickian diffusion. It was stable at $4^{\circ}C$ for at least 2 months. The results suggest that transurethral liquid suppository containing prostaglandin $E_1-loaded$ microemulsion is thought to be a convenient, safe and effective dosage form for $PGE_1$. However, it should be further developed as a more convenient and stable dosage form for $PGE_1$.

• BMB Reports
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• 제40권4호
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• pp.562-570
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• 2007

Soluble or cell-bound IL-1 receptor accessory protein (IL-1RAcP) does not bind IL-1 but rather forms a complex with IL-1 and IL-1 receptor type I (IL-1RI) resulting in signal transduction. Synthetic peptides to various regions in the Ig-like domains of IL-1RAcP were used to produce antibodies and these antibodies were affinity-purified using the respective antigens. An anti-peptide-4 antibody which targets domain III inhibited 70% of IL-$1\beta$-induced productions of IL-6 and PGE2 from 3T3-L1 cells. Anti-peptide-2 or 3 also inhibited IL-1-induced IL-6 production by 30%. However, antipeptide-1 which is directed against domain I had no effect. The antibody was more effective against IL-$1\beta$ compared to IL-$1\alpha$. IL-1-induced IL-6 production was augmented by coincubation with PGE2. The COX inhibitor ibuprofen blocked IL-1-induced IL-6 and PGE2 production. These results confirm that IL-1RAcP is essential for IL-1 signaling and that increased production of IL-6 by IL-1 needs the co-induction of PGE2. However, the effect of PGE2 is independent of expressions of IL-1RI and IL-1RAcP. Our data suggest that domain III of IL-1RAcP may be involved in the formation or stabilization of the IL-1RI/IL-1 complex by binding to epitopes on domain III of the IL-1RI created following IL-1 binding to the IL-1RI.

• Restorative Dentistry and Endodontics
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• 제25권2호
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• pp.193-201
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• 2000

Prostaglandins (PGs) and Leukotrienes (LTs) have been implicated in the genesis of pulpal and periapical inflammation. In this study, the relationships among $PGE_2$, 6-keto-PG $F_1{\alpha}$ (a stable metabolite of $PGI_2$) and $LTB_4$ concentrations in inflamed pulp and periapical lesions were discussed. Pulp tissue were obtained in routine endodontic treatment and periapical lesions in periapical surgery after clinical diagnoses were made. These specimens were divided into four groups as normal pulp group (Control group), acute pulpitis group, chronic pulpitis group, and periapical lesion group. Pulp tissue and periapical lesions were stored in liquid nitrogen. The concentration of $PGE_2$, $PGI_2$ and $LTB_4$ were measured with ELISA. The data were analyzed by one-way ANOVA. Significantly higher levels of $PGE_2$, 6-keto-PG $F_1{\alpha}$ a and $LTB_4$ were found in acute pulpitis group than chronic pulpitis group and periapical lesion group(p<0.05). Periapical lesion group showed significantly higher mean concentrations of $PGE_2$ and $LTB_4$ than chronic pulpitis group. In control and chronic pulpitis group, significant higher levels of $PGI_2$ than $PGE_2$ and $LTB_4$ were found. These results suggested that the high levels of $PGE_2$ and $LTB_4$ in periapical lesions may be due to rich endothelium., fibroblast and lymphocyte known as the main producers of $PGE_2$ and $LTB_4$. $PGI_2$ may be thought to one of the most abundant PGs in normal pulp tissue.

• Journal of Periodontal and Implant Science
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• 제37권4호
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• pp.755-766
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• 2007

Purpose: The purposes of this study were to compare and quantify the expression of $PGE_2$, MMP-14 and TIMP-1 in the gingival tissues of patients with type 2 diabetes mellitus and healthy adults of chronic periodontitis with alveolar bone resorption. Material and methods: Gingival tissue samples were obtained during periodontal surgery or tooth extraction. According to the patient's systemic condition & clinical criteria of gingiva, each gingival sample was devided into three groups. Group 1 (n=8) is clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from systemically healthy 8 patients. Group 2 (n=8) is inflammed gingiva from patients of chronic periodontitis with alveolar bone resorption. Group 3(n=8) is inflammed gingiva from patients of chronic periodontitis with alveolar bone resorption associated with type 2 diabetes. Tissue samples were prepared and analyzed by Western blotting. The quantification of $PGE_2$ MMP-14 and TIMP-1 were performed using a densitometer and statistically analyzed by one-way ANOVA followed by Tukey test. Results: The expressions of MMP-14 and TIMP-1 were showed increasing tendency in group 2 & 3 compared to group 1. The expressions of $PGE_2$, MMP-14 were showed increasing tendency in group 3 compared to group 1 and group 2. According to MMP-14 levels were increasing, $PGE_2$ showed increasing tendency in group 3, and although $PGE_2$, MMP-14 levels were increasing, TIMP-1 levels were similar expressed comparing to group 2. Conclusion: In conclusion, this study demonstrated that the expression levels of MMP-14 and TIMP-1 had increasing tendency in inflammed tissue. It can be assumed that $PGE_2$ and MMP-14 may be partly involved in alveolar bone resorptive process and the progression of periodontal inflammation associated to type 2 DM.

• Biomolecules & Therapeutics
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• 제29권1호
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• pp.64-72
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• 2021

Renal cell carcinoma (RCC) is likely to metastasize to other organs, and is often resistant to conventional chemotherapies. Thymoquinone (TQ), a phytochemical derived from the seeds of Nigella sativa, has been shown to inhibit migration and metastasis in various cancers. In this study, we assessed the effect of TQ on the migratory activity of human RCC Caki-1 cells. We found that treatment with TQ reduced the proteolytic activity of matrix metalloproteinase-9 (MMP-9) in Caki-1 cells. TQ significantly repressed prostaglandin E2 (PGE2) production, its EP2 receptor expression as well as the activation of Akt and p38, the wellknown upstream signal proteins of MMP-9. In addition, treatment with butaprost, a PGE2 agonist, also induced MMP-9 activity and migration/invasion in Caki-1 cells. Moreover, pharmacological inhibitors of PI3K/Akt and p38 remarkably attenuated butaprost-induced Caki-1 cell migration and invasion, implying that activation of PI3K/Akt and p38 is a bridge between the PGE2-EP2 axis and MMP-9-dependent migration and invasion. Taken together, these data suggest that TQ is a promising anti-metastatic drug to treat advanced and metastatic RCC.

• Toxicological Research
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• 제20권1호
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• pp.37-42
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• 2004

본 연구는 Phellinus gilvus(PGE), Phellinus linteus (PLE) 그리고 Phellinus baumil(PBE)의 열수추출물에 대하여 SRB법과 MTT법으로 종양세포주(Sarcoma 180과 P388)를 이용하여 항암활성을 비교ㆍ평가하였다. 종양세포주는 PGE, PLE, PBE(7., 15, 30 ug/ml) 그리고 Doxorubicin(DOX)(0.001～10 mM)으로 처리되었다. 그 결과 DOX, PGE 그리고 PLE는 종양세포주에 대하여 농도의존적으로 억제하는 결과를 보였지만, PBEssm 30 ug/ml의 농도에서만 억제되는 항암활성을 보여주었다. 결론적으로 이 연구에서 사용된 PGE, PLE 및 PBE는 Sarcoma 180과 P388에 항암활성을 보여주었다. PLE는 sarcoma 180종양세포에 가장 효과가 뛰어났으나(p<0.05), SRB법에서는 PGE가 P388에 대해 가장 큰 항암활성을 나타내었다(p<0.05).

• Journal of Radiation Protection and Research
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• 제14권1호
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• pp.8-15
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• 1989

$^{99m}TC,\;^{67}Ga,\;^{131}I,\;^{32}P$각각을 웅성백서에 투여하여 생체에 미치는 혈중 독성의 영향을 측정 비교하였다. 핵종의 투여량은 통상 인체에 주사되는 양을 기준으로하여 조절 하였으며 생화학적 반응 지표로 혈중 BUN, Creatinine, SGOT SGPT와 $PGE_2$의 활성도출 측정하였다. $^{99m}Tc$의 효과로 Creatinine의 변동은 없었으며 BUN, SGOT 및 $PGE_2$활성도가 투여 전에 비하여 증가된 경향을 보였으나 통계적 의의는 없었다. $^{67}Ga,\;^{131}I$ 및 $^{32}P$의 경우 BUN, SGPT 및 SGOT 에서의 증가는 임상적 의의는 없었으나 $PGE_2$는 정상치 보다 크게 상승 하였다. 한편 $^{238}U$이 가장 심한 독성을 나타내었다. 따라서 핵의학에서 이용되는 핵종의 방사성 독성의 효과를 평가할 경우 혈중 $PGE_2$의 측정법이 유용할 것으로 생각된다.

• The Korean Journal of Physiology
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• 제14권2호
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• pp.17-20
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• 1980

This study was undertaken to investigate the effect of the acidosis on the gastric acid secretion in the isolated whole stomach of the rat and the effect of prostaglandin $E_1$ on the gastric acid secretion influenced by the acidosis. Twenty-two male albino rats(Sprague-Dawley strain) were used. The isolated whole stomach from each rat was introduced into the Kreb's solution which was continuously gassed with $95%O_2-5%CO_2$ for 1 hour, after irrigation of the lumen with cold physiological saline$(4^{\circ}C)$. Thereafter, each stomach was irrigated again with 5% dextrose solution (pH 7.4, $37^{\circ}C$), and filled with the dextrose solution. All the stomachs with the dextrose solution were divided into 4 groups according to the Kreb's solutions in which each stomach was incubated for 30 min: 1) control group, in the pH 7.4 solution, 2) $PGE_1$ group, in the pH 7.4 solution containing $5\;{\mu}g/ml$ of $PGE_1$, 3) acid group, in the pH 7.0 solution, and 4) $acid+PGE_1$ group, in the pH 7.0 solution containing $5\;{\mu}g/ml$ of $PGE_1$. After incubatory period, the contents of each stomach were collected and centrifuged(1,500 rpm, room temperature) for 15 min. The acid output in the supernatant was determined with 0.012 N NaOH by means of autotitrator(Dosimat, Metrohm Herisau Co.) at pH 7.4. Results obtained were as follows: 1) The acid output of the acid group increased significantly in comparison with the control value. 2) The acid output of the $acid+PGE_1$ group decreased significantly in comparison with the acid group. It is inferred from the above results that the acidosis facilitates the gastric acid secretion and $PGE_1$ inhibits the gastric acid secretion induced by the acidosis.

• 대한한방부인과학회지
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• 제18권1호
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• pp.55-63
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• 2005

Purpose : 자하거(Hominis Placenta; HP)는 건강한 사람의 태반을 홍제(烘製)하여 건조한 것으로 한의학에서는 기혈(氣血)을 대보(大補)하고 신정(腎精)을 보익(補益)시켜 구병(久病)으로 인한 신체허약(身體虛弱)이나 혹은 체질허약(體質虛弱)과 혈기부족(氣血不足) 및 신허정휴(腎虛精虧) 등 등(證)을 치료(治療)하는데 단미(單味) 또는 복방(複方)에 배오(配伍)하여 쓰여왔다. 또한 자하거는 면역학적으로 골대사 활성이 있는 것으로 알려져 있어 본 연구에서는 자하거의 항골다공증 활성을 분자세포생물학적으로 검정하고자 하였다. Methods : Osteoblast cells에서 자하거가 COX-2 mRNA의 발현과 $PGE_2$ 생합성을 억제시키는지를 관찰하기 위해 먼저 TNF-${\alpha}$, IL-${\beta}$ 와 IL-6를 처리한 후 $PGE_2$의 생합성과 더불어 COX-2 mRNA의 발현을 확인하였다. 그 후 TGF-${\beta}$, 자하거(紫河車)와 이 둘의 조합인 자하거+TGF-${\beta}$가 COX-2 mRNA 발현과 $PGE_2$ 생합성을 저해시키는지 관찰하였다. 또한 자하거가 IL-1${\beta}$로 유발된 흰쥐의 과칼슘혈증을 감소시키는지를 확인하였다. Results : IL-6, IL-1${\beta}$와 TNF-${\alpha}$를 동시에 처리하면 이것을 단독으로 처리한 것과 비교해 볼 때 $PGE_2$의 생합성과 더불어 COX-2 mRNA의 수치가 상승작용을 일으키며 증가하였다. TGF-${\beta}$, 자하거와 이 둘의 조합인 자하거+TGF-${\beta}$은 COX-2 mRNA 발현, $PGE_2$ 생합성 및 골재흡수를 감소시켰다. 자하거(紫河車)는 IL-1${\beta}$, TNF-${\alpha}$와 IL-6 각각 또는 이들의 조합으로 인해 증가하는 COX-2 mRNA 발현과 $PGE_2$ 생성을 감소시키는 반면 COX-1 mRNA 발현에는 유의성 있는 영향을 미치지 않았다. 한편 자하거는 농도의존적으로 IL-1${\beta}$로 유발된 흰쥐의 과칼슘혈증을 감소시켰다. 이러한 결과는 흰쥐의 두개골 골아세포에서 $PGE_2$ 생산에 대한 IL-${\beta}$, TNF-${\alpha}$, IL-6의 상승작용이 COX-2의 유전자 발현 증가에 기인함을 보여주었다. Conclusions : 이러한 결과들로부터 자하거가 골대사과정중 골재흡수를 억제하는데 효과적임을 밝히게 되었으며, 자하거의 골다공증의 억제기전이 골재흡수관련 단백질들의 전사조절에 있음을 최초로 해명하게 되었다.