• Childhood Kidney Diseases
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• 제9권2호
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• pp.183-192
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• 2005

목 적 : 소아 HSPN의 임상 경과와 이에 영향을 미치는 예후 인자를 조사하였다. 방 법 : 소아 HSPN 환자 75명(남아 44명, 여아 31명)을 대상으로 하였으며 발병연령은 $8.0{\pm}3.1$세(2.3-l5.3세)였고 추적관찰 기간은 $4.3{\pm}3.6$년(1.0-17.1년)이었다. 신생검은 24명(32$\%$)에서 시행되었다. 발병시 임상 양상과 검사 결과를 조사하였으며, 대상 환자들의 RAS 유전자의 다형성(ACE 유전자의 I/D 다형성, AGT 유전자의 M235T 다형성, AGTR 유전자의 A1166C 다형성)에 대해 검사하였다. 발병시와 마지막 추적관찰시 임상 상태는 다음과 같이 4군으로 분류하였다: A, 정상; B, 정도의 소변이상; C, 활동성 신질환(신증후군 범위의 단백뇨) 또는 고혈압 소견을 보이면서 혈청 크레아티닌 1.5 mg/dL 이하; D, 신부전. 결 과 : 발병시 환자들의 임상 상태는 26명(35$\%$)이 B, 45명(51$\%$)이 C였고 D가 3명(4$\%$)이었다. RAS 유전자 다형성의 분포는 100명의 건강한 대조군과 다르지 않았다. 마지막 추적관찰시 환자들의 임상 상태는 A가 23명(31$\%$), B가 38명(50$\%$), C가 9명(12$\%$), D가 5명(7$\%$)이었다. Multiple logistic regression 결과 발병 연령과 발병시 단백뇨의 양이 유의한 예후 인자로 확인되었다. RAS 유전자는 HSPN의 예후 인자로 통계학적 유의성이 없었다. 결 론 : 본 연구에서는 발병 연령이 높을수록, 발병시 단백뇨의 양이 많을수록 소아 HSPN의 예후가 나쁜 것으로 나타났고 RAS 유전자는 HSPN의 예후와 상관 관계가 없었다. 더 정확한 연구를 위해서는 더 많은 수의 환자를 대상으로 전향적인 연구가 필요하리라 생각한다.

• Molecules and Cells
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• 제26권5호
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• pp.436-442
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• 2008

Osteoclasts are multinucleated cells with the unique ability to resorb bone. Elevated activity of these cells under pathologic conditions leads to the progression of bone erosion that occurs in osteoporosis, periodontal disease, and rheumatoid arthritis. Thus, the regulation of osteoclast apoptosis is important for bone homeostasis. In this study, we examined the effects of the Janus tyrosine kinase 2 specific inhibitor AG490 on osteoclast apoptosis. We found that AG490 greatly inhibited osteoclast apoptosis. AG490 stimulated the phosphorylation of Akt and ERK. Adenovirus-mediated expression of dominant negative (DN)-Akt and DN-Ras in osteoclasts inhibited the survival of osteoclasts despite the presence of AG490. Cytochrome c release during osteoclast apoptosis was inhibited by AG490 treatment, but this effect was inhibited in the presence of LY294002 or U0126. AG490 suppressed the pro-apoptotic proteins Bad and Bim, which was inhibited in osteoclasts infected with DN-Akt and DN-Ras adenovirus. In addition, constitutively active MEK and myristoylated-Akt adenovirus suppressed the cleavage of pro-caspase-9 and -3 and inhibited osteoclast apoptosis induced by etoposide. Taken together, our results suggest that AG490 inhibited cytochrome c release into the cytosol at least partly by inhibiting the pro-apoptotic proteins Bad and Bim, which in turn suppressed caspase-9 and -3 activation, thereby inhibiting osteoclast apoptosis.

• 약학회지
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• 제36권6호
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• pp.529-537
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• 1992

To investigate the effect of ursolic acid on the expression of oncogenes in tumor cells of mice, sarcoma 180 ascites tumor cells were implanted into the left groin of ICR mice and the tumor bearing mice were treated with ursolic acid. The expression of oncogenes were measured by in situ hybridization method. Ursolic acid significantly reduced the expression of oncogenes in the tumor cells. Therefore, it can be said that the prestated anticarcinogenic effect of ursolic acid could be partly ascribed to the mechanism included in the oncogene´s transcription level.

• 한국독성학회:학술대회논문집
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• 한국독성학회 1998년도 국제심포지움 및 추계학술대회
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• pp.36-36
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• 1998

Tumorigenicity of benzo(a)pyrene (BP) and benzo(a)pyrene diol epoxides ((+)BPDE-1, (-)BPDE-1) was investigated in transgenic TG-AC mice carrying v-Ha-ras oncogene fused to the promoter of the mouse embryonic a-like, z-globin gene. Animals were topically treated twice per week for 25weeks with BPDE (10$\mu$g/mouse) and BP (10, 20, 40$\mu$g/mouse). In addition, animals were treated with BPDE or BP (initiated) followed by TPA (2$\times$2.5$\mu$g/week, for 4 weeks) for promotion study. In the continuous treatment of BPDE or BP, animals treated with 40$\mu$g BP showed $100\%$ tumor response after 20 weeks, $40\%$ of mice for 20$\mu$g BP, and $20\%$ for (+)BPDE-1, but (-)BPDE-1 and 10$\mu$g BP did not show any tumor response. After 25 weeks, most tumors turned out to be carcinomas in animals treated with 40$\mu$g BP. In BPDE or BP/TPA Initiation-promotion study, papilloma response occurred earlier (6 weeks after TPA treatment) than in continuously treated animals with BPDE or BP. RT-PCR assay for transgene expression showed that BP or BPOE was not transgene dependent in its tumorigenicity, but TPA was. Several Cytokine genes(TGF-a, TNF-a) and c-myc gene expressions were monitored in skin tissues during BP carcinogenesis. In early stage of BP treatment, the gene expressions were elevated(c-myc,TGF-a) or unchanged(TNF-a) compared to control, but the levels were gradually decreased during both middle and late stages of cacinogenesis, Gene expression levels of skin papillomas in acetone initiated-TPA promoted animals were close to those of middle stage or between middle and late stages. i-NOS was also highly expressed in carcinoma and papilloma, These data suggest that transgene expressions of TG-AC mice were not dependent on BP carcinogenesis and that TG-AC mice were more sensitive to TPA regardless of types of initiators. In addition, genes(TGF-a, c-myc, TNF-a, i-NOS) were modulated in the skin during BP cacinogenesis or TPA promotion.

• 한국식품위생안전성학회:학술대회논문집
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• 한국식품위생안전성학회 2001년도 The Asia-Pacific Conference on Reproductive Biology and Environmental Sciences
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• pp.71-73
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• 2001

• 한국환경성돌연변이발암원학회지
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• 제26권3호
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• pp.77-85
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• 2006

2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin(TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although TCDD is recognized as potent carcinogens, relatively little is known about their role in the tumor promotion and carcinogenesis. It is known that TCDD can increase of cancer risk from various types of tissue by a mechanism possibly involving the aryl hydrocarbon receptor (AhR) activation. In this study, effects of TCDD on cellular proliferation of normal human skin and lung fibroblasts, Detroit551 and WI38 cells were investigated. In addition, to enhance our understanding of TCDD-mediated carcinogenesis, we have investigated process in which expression of Erk1/2, cyclinD1, oncogene such as Ha-ras and c-myc, and their cognate signaling pathway. TCDD that are potent activators of AhR-mediated activity was found to induce significant increase of cytochrome P4501A1 mRNA expression, suggesting a presence of functional AhR. These results support that CYP1A1 enzyme may be involved in the generation of TCDD-induced toxicity. Moreover mitogen-activated protein kinases (MARKs) phosphorylation and cyclin D1 overexpression are induced by TCDD, which corresponded with the progression of cellular proliferation. However, TCDD did not affected Ha-ras and c-myc mRNA expression. Taken together, it seems that TCDD are could be a part of cellular proliferation in non-tumorigenic normal human cells such as Detroit551 and WI38 cells through the upregulation of MAPKs signaling pathway regulating growth of cell population. Therefore, AhR-activating TCDD could potentially contribute to tumor promotion and Detroit551 and WI38 cells have been used as a detection system of tumorigenic effects of TCDD.

• Archives of Pharmacal Research
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• 제29권3호
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• pp.224-234
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• 2006

We employed human SK-MEL-28 cells as a model system to identify cellular proteins that accompany N-(4-methyl)phenyl-O-(4-methoxy)phenyl-thionocarbamate (MMTC)-induced apoptosis based on a proteomic approach. Cell viability tests revealed that SK-MEL-28 skin cancer cells underwent more cell death than normal HaCaT cells in a dose-dependent manner after treatment with MMTC. Two-dimensional electrophoresis in conjunction with matrixassisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis or computer matching with a protein database further revealed that the MMTC-induced apoptosis is accompanied by increased levels of caspase-1, checkpoint suppressor-1, caspase-4, NF-kB inhibitor, AP-2, c-Jun-N-terminal kinase, melanoma inhibitor, granzyme K, G1/S specific cyclin D3, cystein rich protein, Ras-related protein Rab-37 or Ras-related protein Rab-13, and reduced levels of EMS (oncogene), ATP synthase, tyrosine-phosphatase, Cdc25c, 14-3-3 protein or specific structure of nuclear receptor. The migration suppressing effect of MMTC on SK-MEL-28 cell was tested. MMTC suppressed the metastasis of SK-MEL-8 cells. It was also identified that MMTC had little angiogenic effect because it did not suppress the proliferation of HUVEC cell line. These results suggest that MMTC is a novel chemotherapeutic and metastatic agents against the SK-MEL-28 human melanoma cell line.

• Journal of Acupuncture Research
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• 제18권4호
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• pp.101-115
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• 2001

Objective : To characterize the antitumorigenic potential of Apamin, one of the major components of bee venom, its effects on cell proliferation and the mitogen-activated protein kinase (MAPK) signal transduction pathway were characterized using the human melanoma cell line SK-MEL-2. Methods & Results : Cell counting analysis for cell death demonstrated that consistent with a previous results, SK-MEL-2 cells treated with $0.5-2.0{\mu}g/ml$ of Apamin showed no recognizable cytotoxic effect whereas detectable induction of cell death was identified at concentrations over $5.0{\mu}g/ml$. [3H]thymidine incorporation assay for cell proliferation demonstrated that DNA replication of SK-MEL-2 cells is inhibited by Apamin in a dose- and time-dependent manner. To explore whether Apamin-induced growth suppression is associated with the MAPK signaling pathway, phosphorylation of Erk, a function mediator of MAPK growth-stimulating signal, was examined Western blot assay using a phospho-specific Erkl/2 antibody. A significant increase of Erkl/2 phosphorylation level was observed in Apamin-treated cells compared with untreated control cells. Qantitative RT-PCR analysis revealed that Apamin inhibit expression of MAPK downstream genes such as c-Jun, c-Fos, and cyclin D1 but not expression of MAPK pathway component genes including Ha-Ras, c-Raf-1, MEK1, and Erk. Conclusion : It is strongly suggested that the antitumorigenic activity of Apamin might result in part from its inhibitory effect on the MAPK signaling pathway in human melanoma cells SK-MEL-2.

• Parasites, Hosts and Diseases
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• 제53권4호
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• pp.421-430
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• 2015

The parasite Plasmodium falciparum causes severe malaria and is the most dangerous to humans. However, it exhibits resistance to their drugs. Farnesyltransferase has been identified in pathogenic protozoa of the genera Plasmodium and the target of farnesyltransferase includes Ras family. Therefore, the inhibition of farnesyltransferase has been suggested as a new strategy for the treatment of malaria. However, the exact functional mechanism of this agent is still unknown. In addition, the effect of farnesyltransferase inhibitor (FTIs) on mitochondrial level of malaria parasites is not fully understood. In this study, therefore, the effect of a FTI R115777 on the function of mitochondria of P. falciparum was investigated experimentally. As a result, FTI R115777 was found to suppress the infection rate of malaria parasites under in vitro condition. It also reduces the copy number of mtDNA-encoded cytochrome c oxidase III. In addition, the mitochondrial membrane potential (${\Delta}{\Psi}m$) and the green fluorescence intensity of MitoTracker were decreased by FTI R115777. Chloroquine and atovaquone were measured by the mtDNA copy number as mitochondrial non-specific or specific inhibitor, respectively. Chloroquine did not affect the copy number of mtDNA-encoded cytochrome c oxidase III, while atovaquone induced to change the mtDNA copy number. These results suggest that FTI R115777 has strong influence on the mitochondrial function of P. falciparum. It may have therapeutic potential for malaria by targeting the mitochondria of parasites.

• 한국산학기술학회논문지
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• 제12권5호
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• pp.2187-2196
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• 2011

본 연구는 리듬청각자극을 이용한 보행훈련이 뇌졸중 환자의 보행의 대칭성에 미치는 효과를 알아보고자 하였다. 6개월이 지난 만성 뇌졸중환자 40명을 대상으로 중재 방법에 따라 4군으로 나누었다. A군은 편안한속도로 마비측에 청각자극을 주고 B군은 편안한속도로 비마비측에 청각자극을 주고 C군은 10%증가된 속도로 마비측에 청각자극을 주고 D군은 10%증가시킨 속도로 비마비측에 청각자극을 주었다. 각 군의 환자에게 5분동안 청각자극을 주며 보행훈련을 시행하였다. 보행분석 시스템을 이용하여 보행의 시간적인 변수를 측정하였으며 계산공식을 이용하여 보행의 대칭성을 구하였다. 보시간은 A군을 제외한 모든 군에서 유의하게 감소하였고(p<.05), 보행대칭성도 A군을 제외한 모든 군에서 유의하게 개선되었다(p<.05). 분속수는 A군을 제외한 모든 군에서 유의하게 증가하였고(p<.05), 속도는 모든 군에서 증가하지 않았다. 이 결과를 통해 리듬청각자극이 보행의 대칭성을 개선하는데 효과적임을 확인하였으며 뇌졸중 환자의 보행훈련에 효과적인 방법으로 적용할 수 있으리라 생각한다.