• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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• pp.110-110
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• 2001

To compare skin irritation and cytotoxicity of anti-wrinkle agents, we examined skin irritation of six anti-wrinkle agents (ascorbic acid, glycolic acid, all trans-retinoic acid, ginseng extract, retinol, EB) in New Zeland white rabbit.(omitted)

• Nutrition Research and Practice
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• 제3권2호
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• pp.77-83
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• 2009

Retinoic acids (RAs) modulate growth, differentiation, and apoptosis in normal, pre-malignant & malignant cells. In the present study, the effects of RA isomers (all-trans RA, 13-cis RA, and 9-cis RA) on the cell signal transduction of human breast cancer cells have been studied. The relationship between RAs and an enzymatic antioxidant system was also determined. Estrogen-receptor (ER) positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells were treated with different doses of each RA isomers, all-trans RA, 13-cis RA, or 9-cis RA. Treatment of RA isomers inhibited cell viability and induced apoptosis of MCF-7 cells as a result of increased caspase activity in cytoplasm and cytochrome C released from mitochondria. All-trans RA was the most effective RA isomer in both cell growth inhibition and induction of apoptosis in MCF-7 cells. However, no significant effect of RA isomers was observed on the cell growth or apoptosis in ER-negative MDA-MB-231 cells. In addition, activities of antioxidant enzymes such as catalase and glutathione peroxidase were decreased effectively after treatment of RA in MCF-7 cells, whereas SOD activity was rarely affected. Thus, the present data suggest that all-trans RA is the most potential inducer of apoptosis and modulator of antioxidant enzymes among RA isomers in MCF-7 human breast cancer cells.

• 한방안이비인후피부과학회지
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• 제30권1호
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• pp.106-117
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• 2017

Objectives : 갈근의 피부 보습 효과에 대해 알아보기 위해 본 연구를 진행하였다. Methods : HaCaT 세포주에 갈근 에탄올 추출물을 처리하였고 Retinoic Acid $1{\mu}M$을 양성 대조군으로 사용하였다. MTT assay, RT-PCR, Hyaluronidase enzyme assay, HA-ELISA kit를 통해 Hyaluronic Acid의 합성량, Hyaluronidase 저해율, 농도별 Hyaluronic Acid 생성량을 측정하였다. 더불어 실제로 피부에 도포 시 보습 능력이 있는지 등에 대하여 확인하였다. Results : 갈근 에탄올 추출물은 뚜렷한 세포독성을 나타내지는 않았고, 모든 농도에서 Hyaluronic Acid 합성과 관련된 hyaluronic acid synthase 2 유전자가 발현되었고, 실제로 Hyaluronic Acid가 생성되는 것을 확인하였다. 임상 효능 평가에서는 유의성 있는 결과를 얻을 수는 없었다. Conclusions : 갈근을 한방 외용제로 사용할 때 유의성 있는 효과를 나타낼 수 있을 것으로 기대할 수 있으며, 실험 결과를 토대로 갈근의 최적 사용 농도를 결정하기 위한 추가적 연구와 복합 처방으로 사용했을 경우에 대한 연구가 추가적으로 진행된다면 한방 외용제로서 잠재적인 가치가 있을 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제19권2호
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• pp.105-109
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• 2015

NgR1, a Nogo receptor, is involved in inhibition of neurite outgrowth and axonal regeneration and regulation of synaptic plasticity. P19 embryonal carcinoma cells were induced to differentiate into neuron-like cells using all trans-retinoic acid and the presence and/or function of cellular molecules, such as NgR1, NMDA receptors and STAT3, were examined. Neuronally differentiated P19 cells expressed the mRNA and protein of NgR1, which could stimulate the phosphorylation of STAT3 when activated by Nogo-P4 peptide, an active segment of Nogo-66. During the whole period of differentiation, mRNAs of all of the NMDA receptor subtypes tested (NR1, NR2A-2D) were consistently expressed, which meant that neuronally differentiated P19 cells maintained some characteristics of neurons, especially central nervous system neurons. Our results suggests that neuronally differentiated P19 cells expressing NgR1 may be an efficient and convenient in vitro model for studying the molecular mechanism of cellular events that involve NgR1 and its binding partners, and for screening compounds that activate or inhibit NgR1.

• 한국식품영양과학회지
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• 제23권5호
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• pp.799-804
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• 1994

천연물에서 직접적인 암세포 살해능을 가지며, 동시에 중증의 백혈구 감소증을 억제시킬 수 있는 물질을 탐색하기 위하여 암세포주인 U937 human lymphoma cell과 정상면역 세포인 lymphocyte에 대한 권백 수침 엑기스의 암세포 살해능과, 현재 임상에서 응용되고 있는 화학요법제인 retinoic acid, doxorubicine, cyclopho-sphamide와의 병용요법이 암세포(U937)와 정상세포(lymphocyte)에 미치는 영향을 MTT 분석법을 이용하여 비교 관찰하여 다음과 같은 결과를 얻었다. 권백 수침 엑기스 단독첨가시 권백 수침 엑기스는 암세포인 U937 human iymphoma cell의 성장을 유의적으로 억제시켰으며, 정상면역세포인 lymphocyte에는 영향을 미치지 않았따. 권백 수침 엑기스와 호학요법제를 병용 첨가시 화학요법제를 단독 처리했을 때 보다 권백 수침 엑기스(1mg/ml)와 화학요법제를 병용하였을 때, U937의 세포살해능의 현저히 증가되었고, 한편 lymphocyte의 세포살해능은 감소하였다. 이상의 결과에서 화학요법제와 권백을 병용 투여함으로서 암세포 살해능은 증가되고, 정상세포 살해능은 감소되었으므로 화학요법제의 가장 큰 부작용인 immunosupression 중 $leucopeenia^{20~30}$를 감소시킬 수를 감소시킬 수 있을 것으로 사료된다.

• 대한의생명과학회지
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• 제16권1호
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• pp.1-9
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• 2010

In order to understand the effects of all-trans-RA on palate development, RA was injected into the abdominal cavity of pregnant mice and then the embryos were taken in the following days and analyzed morphologically as well as molecular biologically. When RA was administered at the stage of E11 or E15, the overall craniofacial development was retarded. The length from jaw to eye was shortened, compared to that of normal group. When the E11 embryos were exposed to RA, cleft lip was also found along with the cleft palate. In vitro palate culture experiment also revealed that RA caused cleft palate. When RT-PCR was performed, early stage administration of RA at E11 inhibited the upregulation of Hoxa7 expression at E15 through E17. Whereas in control group, high level of Hoxa7 expression was detected in the palate of E15 to E17. In the case of Bax, the expression was decreased from E16, while remaining constant in control group. When TUNEL analysis was performed following the RA treatment at E15, TUNEL positive cells were detected in the mesenchymal cells as well as epithelial cells of palatal shelves of E16 and in E17 embryos. Whereas in normal control, TUNEL positive cells were observed mostly at the epithelium around the nasal cavity and oral cavity where rugae is made. These results altogether indicate that exposure to RA during palate development causes facial deformity including cleft palate and cleft lip by modulating the expression of homeotic genes such as Hoxa7 as well as an apoptosis-related gene, Bax, and thus malregulating the apoptosis.

• 대한핵의학회지
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• 제35권3호
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• pp.117-124
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• 2001

Serum thyroglobulin measurement and I-131 whole-body scintigraphy (WBS) are well-established methods for the detection of recurrence in the follow-up of patients with thyroid carcinoma. However, inconsistent results are observed frequently, and these two methods are not always able to detect recurrence. In some patients, serum thyroglobulin level is elevated but the WBS is negative, because the recurrent tumor is too small and below the sensitivity of the diagnostic scan, or there is a dissociation between thyroglobulin synthesis and the iodine frapping mechanism. In such cases, various nuclear imaging methods including Tl-201 Tc-99m-sestamibi, and F-18-FDG PET can be used besides anatomical imaging methods. Among them, FDG PET localizes recurrent lesions in WBS-negative thyroid carcinoma with high accuracy. Several studies have suggested that empirical high-dose I-131 therapy resulted in a high rate of visualization in post-therapy scans with evidence of subsequent improvement. An important question is when to operate on patients with recurrent tumor. We believe that surgical removal is the best means of treatment for patients with localized persistent tumor, despite the high-dose I-131 therapy. with tumor in thyroid remnant, and with isolated recurrence in the lymph node, lung or bone. In addition, we recommend palliative resection of locally unresectable mass with subsequent treatment with high-dose I-131 therapy. Before I-131 therapy, the evaluation of sodium-iodide symporter expression in thyroid carcinoma can predict iodine uptake. Retinoic acid is known to induce redifferentiation, and to enhance I-131 uptake in thyroid carcinoma. Retinoic acid therapy may represent an alternative approach before high-dose I-131 therapy.

• Biomolecules & Therapeutics
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• 제26권4호
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• pp.417-423
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• 2018

Extracellular interleukin 1 alpha (IL-$1{\alpha}$) released from keratinocytes is one of the endpoints for in vitro assessments of skin irritancy. Although cells dying via primary skin irritation undergo apoptosis as well as necrosis, IL-$1{\alpha}$ is not released in apoptotic cells. On the other hand, active secretion has been identified in interleukin-1 receptor antagonist (IL-1ra), which was discovered to be a common, upregulated, differentially-expressed gene in a microarray analysis performed with keratinocytes treated using cytotoxic doses of chemicals. This study examined whether and how IL-1ra, particularly extracellularly released IL-1ra, was involved in chemically-induced keratinocyte cytotoxicity and skin irritation. Primary cultured normal adult skin keratinocytes were treated with cytotoxic doses of chemicals (hydroquinone, retinoic acid, sodium lauryl sulfate, or urshiol) with or without recombinant IL-1ra treatment. Mouse skin was administered irritant concentrations of hydroquinone or retinoic acid. IL-1ra (mRNA and/or intracellular/extracellularly released protein) levels increased in the chemically treated cultured keratinocytes with IL-$1{\alpha}$ and IL-$1{\beta}$ mRNAs and in the chemically exposed epidermis of the mouse skin. Recombinant IL-1ra treatment significantly reduced the chemically-induced apoptotic death and intracellular/extracellularly released IL-$1{\alpha}$ and IL-$1{\beta}$ in keratinocytes. Collectively, extracellular IL-1ra released from keratinocytes could be a compensatory mechanism to reduce the chemically-induced keratinocyte apoptosis by antagonism to IL-$1{\alpha}$ and IL-$1{\beta}$, suggesting potential applications to predict skin irritation.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.251-256
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• 2009

Previous observations suggest that Bis, a Bcl-2-binding protein, may playa role the neuronal and glial differentiation in vivo. To examine this further, we investigated Bis expression during the in vitro differentiation of P19 embryonic carcinoma cells induced by retinoic acid (RA). Western blotting and RT-PCR assays showed that Bis expression was temporarily decreased during the free floating stage and then began to increase on day 6 after the induction of differentiation. Double immunostaining indicated that Bis-expressing cells do not express several markers of differentiation, including NeuN, MAP-2 and Tuj-1. However, some of the Bis-expressing cells also were stained with GFAP-antibodies, indicating that Bis is involved glial differentiation. Using an shRNA strategy, we developed bis-knock down P19 cells and compared them with control P19 cells for the expression of NeuroD, Mash-1 and GFAP during RA-induced differentiation. Among these, only GFAP induction was significantly attenuated in Pl9-dnbis cells and the population showing GFAP immunoreactivity was also decreased. It is noteworthy that distribution of mature neurons and migrating neurons was disorganized, and the close association of migrating neuroblasts with astrocytes was not observed in P19-dnbis cells. These results suggest that Bis is involved in the migration-inducing activity of glial cells.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7265-7270
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• 2013

Objective: The present study was designed to investigate the probable mechanisms of synthetic retinoid 4-amino-2-tri-fluoromethyl-phenyl ester (ATPR) inhibition of the proliferation and migration of A549 human lung carcinoma cells. Materials and Methods: After the A549 cells were treated with different concentrations of ATPR or all-trans retinoic acid (ATRA) for 72 h, scratch-wound assays were performed to assess migration. Immunofluorescence was used to determine the distribution of CAV1 and $RXR{\alpha}$, while expression of CAV1, MLCK, MLC, P38, and phosphorylation of MLC and P38 were detected by Western blotting. Results: ATPR could block the migration of A549 cells. The relative migration rate of ML-7 group had significantly decreased compared with control group. In addition, ATPR decreased the expression of a migration related proteins, MLCK, and phosphorylation of MLC and P38. ATPR could also influence the expression of RARs or RXRs. At the same time, CAV1 accumulated at cell membranes, and $RXR{\alpha}$ relocated to the nucleus after ATPR treatment. Conclusions: Caveolae may be implicate in the transport of ATPR to the nucleus. Change in the expression and distribution of $RXR{\alpha}$ may be implicated in ATPR inhibition of A549 cell proliferation. The mechanisms of ATPR reduction in A549 cell migration may be associated with expression of MLCK and phosphorylation of MLC and P38.