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( Munkhtsetseg Tudev ),( Yong Lim ),( Eun Seok Park ),( Won Sik Kim ),( Il Ho Lim ),( Jae Hwan Kwak ),( Jae Kyung Jung ),( Jin Tae Hong ),( Hwan Soo Yoo ),( Mi Yea Lee ),( Myoung Yun Pyo ),( Yeo Pyo Y 한국응용약물학회 2011 Biomolecules & Therapeutics(구 응용약물학회지) Vol.19 No.2
Atherosclerosis and post-angiography restenosis are associated with intimal thickening and concomitant vascular smooth muscle cell (VSMC) proliferation. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and anti-tumor activities. The goal of the present study was to enhance the inhibitory effects of obovatol to improve its potential as a preventive or therapeutic agent in atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic smooth muscle cells (RASMCs) was examined in the presence or absence of a newly synthesized obovatol derivative, OD78. The observed anti-proliferative effect of OD78 was further investigated by cell counting and [3H]-thymi-dine incorporation assays. Treatment with 1-4 μM OD78 dose-dependently inhibited the proliferation and DNA synthesis of 25 ng/ ml PDGF-BB-stimulated RASMCs. Accordingly, OD78 blocked PDGF-BB-induced progression from the G0/G1 to S phase of the cell cycle in synchronized cells. OD78 decreased the expression levels of CDK4, cyclin E, and cyclin D1 proteins, as well as the phosphorylation of retinoblastoma protein and proliferating cell nuclear antigen; however, it did not change the CDK2 expression level. In addition, OD78 inhibited downregulation of the cyclin-dependent kinase inhibitor (CKI) p27kip1. However, OD78 did not affect the CKI p21cip1 or phosphorylation of early PDGF signaling pathway. These results suggest that OD78 may inhibit PDGF-BB-induced RASMC proliferation by perturbing cell cycle progression, potentially through p27kip1 pathway activation. Consequently, OD78 may be developed as a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.
Yeo-Pyo Yun,Munkhtsetseg Tudev,박은석,Won-Shik Kim,Il-Ho Lim,Mi-Yea Lee,Heesoon Lee,Jae-Kyung Jung,Jin-Tae Hong,유환수,Myung-Koo Lee,Myoung-Yun Pyo,Yeo Pyo Yun,임용 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.7
The proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in the formation and progression of intimal thickening in early-phase atherosclerosis and in restenosis after vascular injury. Tumor necrosis factor-α (TNF-α) is released from macrophages in atherosclerotic lesions and from neointimal vascular smooth muscle cells after balloon-injury. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and antitumor activities. The goal of this study was to examine the cardioprotective effects of the obovatol derivative OD 78 on the TNF-α-induced proliferation and migration of rat aortic smooth muscle cells (RASMCs). The antiproliferative effects of OD 78 on RASMCs were examined by cell counting and [³H]-thymidine incorporation assays. Treatment of cells with 1-4 μM OD 78 inhibited the proliferation and DNA synthesis of TNF-α-stimulated RASMCs in a concentration-dependent manner, without cytotoxicity. Treatment with OD 78 inhibited TNF-α-mediated p38 phosphorylation, but did not change the activation of extracellular signal-regulated kinase or c-Jun N-terminal kinase. Furthermore, treatment with OD 78 decreased TNF-α-induced levels of cyclin E, cyclin D1, CDK2, proliferating cell nuclear antigen, and phosphorylated retinoblastoma protein, but not the CDK4 expression level. Also, OD 78 inhibits the migration of TNF-α-induced RASMC in transwells. OD 78 treatment strongly decreased matrix metalloproteinase-9 (MMP-9) expression in a dose-dependent manner, but the MMP-2 expression was unchanged. These results show that OD 78 may be developed as a potential antiproliferative agent for the treatment of angioplasty restenosis and atherosclerosis.
Epidemiology of Pancreatic Cancer in Mongolia Last Decade
( Lkhagva-ochir Tovuu ),( Undarmaa Tudev ),( Enkhjargal Bayar-saikhan ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Pancreatic cancer is one of the highest mortality rates in the world and often remains undiagnosed until it is at a late stage, resulting in the majority of tumors being unsuitable for surgical resection. Improving the results of chemotherapy has been slow, and novel approaches to systemic treatment are needed. The aim of the present study was to update the epidemiology of pancreatic cancer in Mongolia last decade from the National Cancer Center of Mongolia database. Methods: All patients hospitalized for pancreatic cancer in NCCM from 2007 to 2016 were included. Patient and stays (length, type of support, institutions) characteristics were studied. Results: A total of 1003 (52% men, median age 61 years) new cases were diagnosed for pancreatic cancer last decade, accounting for a 2.7 times increase compared with 2007 and 2016. Overall, early stage pancreatic cancer was 11.7%, among 16% of patients were operated on. Mortality rate was 86.5%. Conclusions: Approximately 1003 new cases of pancreatic cancer were observed in Mongolia in last decade. The incidence and mortality rate to tendency increasing. We need more to improve diagnostic capacity and treatment rate.
동맥혈관 평활근세포 증식에 대한 오보바톨 유도체(A-8)의 억제효과
임용(Yong Lim),이미애(Mi-Yea Lee),투데브멍흐(Munkhtsetseg Tudev),박은석(Eun-Seok Park),정재경(Jae-Kyung Jung),윤여표(Yeo-Pyo Yun) 대한약학회 2011 약학회지 Vol.55 No.2
Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development and progression of proliferative cardiovascular diseases, including hypertension and atherosclerosis. To find antiproliferative agent (A)-8 had inhibitory effect on VSMCs proliferation. Therefore, we examined the antiproliferative effect of A-8, a newly synthesized obovatol derivative. To investigate the antiproliferative effect of A-8, we examined cell counting and [3H]-thymidine incorporation assays. The pre-incubation of A-8 (1~4 μM) significantly inhibited proliferation and DNA synthesis of 5% fetal bovine serum (FBS)-stimulated rat aortic VSMCs in concentration-dependent manner. Whereas, A-8 did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by WST-1 assay. In addition, A-8 significantly inhibited 5% FBS-induced cell cycle progression in rat aortic VSMCs. These results show that A-8 may be developed as a potential antiproliferative agent for treatment of angioplasty restenosis and atherosclerosis. Furthermore, A-8 should be examined for further clinical application either as a single agent or in combination with other angioplasty restenosis or atherosclerosis agents.
Park, Haing Kee,Park, Eui-Chul,Bae, Sung Won,Park, Mi Young,Kim, Seon Woon,Yoo, Hwan Soo,Tudev, Munkhtsetseg,Ko, Young Hye,Choi, Yoon-Ho,Kim, Sungjoo,Kim, Dong-Ik,Kim, Young Wook,Lee, Byung Boong,Yoon American Heart Association 2006 Circulation Vol.114 No.9
<P>BACKGROUND: We intended to identify proteins that are differentially expressed in human atherosclerotic plaques. METHODS AND RESULTS: Comparative 2-dimensional electrophoretic analysis on carotid atherosclerotic endarterectomy specimens (n = 10) revealed that heat shock protein 27 (Hsp27) expression was significantly increased in the nearby normal-appearing area compared with the plaque core area from the same vessel specimen, which was further confirmed by Western blot analysis. The Hsp27 expression in the adjacent normal-appearing vessel areas was much higher than that in nonatherosclerotic reference arteries. The phosphorylation of Hsp27 showed a gradation in the degree of phosphorylation: greatest in the reference arteries, intermediate in the adjacent normal-appearing area, and lowest in plaque core area. Immunohistochemical analysis showed that the phosphorylation of Hsp27 of smooth muscle cells in the carotid endarterectomy specimens was decreased compared with that in the reference artery specimen. The mean plasma level of Hsp27 was significantly higher in patients with acute coronary syndrome (ACS) (n = 27; 106.1 +/- 74.1 ng/mL) than in the normal reference subjects (n = 29; 45.8 +/- 29.5 ng/mL; P < 0.005). The plasma levels of Hsp27 were significantly correlated with those of heat shock protein 70 (Hsp70) (r = 0.422, P < 0.0005), with adjustment for ACS/reference status. CONCLUSIONS: In the atherosclerotic lesion, Hsp27 expression is increased in the normal-appearing vessel adjacent to atherosclerotic plaque, whereas levels in the plaque itself are significantly decreased. Both plaque and adjacent artery show decreased Hsp27 phosphorylation compared with reference vessel. In ACS, plasma Hsp27 and Hsp70 are increased, and levels of Hsp27 correlate with Hsp70, C-reactive protein, and CD40L levels.</P>