• Title/Summary/Keyword: $P2Y_{12}$ receptor

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The investigation of an age as a prognostic factor of breast cancer (유방암의 예후인자로서 젊은 연령에 대한 고찰)

  • No, Dong-Yeong
    • Journal of Korea Association of Health Promotion
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    • v.2 no.1
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    • pp.39-46
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    • 2004
  • Purpose:It has been known that the prognosis of a young woman's breast cancer is Poorer than the other woman However, the effect of age on the prognosis is not well-defined We performed this study to investigate age as a prognostic factor of breast cancer. Materials and Methods : A retrospective study was conducted for 3209 breast cancer patients who underwent operations in Department of Surgery, Seoul National University Hospital from January 1981 to December 2000. Patients were divided into two groups, young age(≤35) and old age(>35) groups. And tumor stage, histopathologic characteristics(such as histology, nuclear grade, histologic grade, hormonal receptor, etc), overall survival and disease free survival rates were compared between age groups. Results . The age ranged from 17 to 88 years. 396 patients(12.3%) were included in young age group(median=32) and 2813 Patients(87.7%) in old age group(median=47).There are more advanced stages and poor nuclear grades in young age group(p=0.000, p=0.003), By log-rank test, the young age group had poorer overall survival and disease free survival rates(p<0.05, p=0.0002). Although, the young age group had more advanced TMN stages(p=0.000) and poorer nuclear grade than the old age group(p=0.003) in multi variate analysis, the age was not a significant independent prognostic factor. (P=0.642)Conclusion: Our study showed that the age was not a significant independent prognostic factor.

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Influence of FCCP on Catecholamine Release in the Rat Adrenal Medulla

  • Lim, Dong-Yoon;Jo, Seong-Ho;Kee, Young-Woo;Lim, Ji-Yeon;Choi, Deok-Ho;Baek, Young-Joo;Hong, Soon-Pyo
    • Biomolecules & Therapeutics
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    • v.12 no.3
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    • pp.165-174
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    • 2004
  • The aim of the present study was to investigate the effect of FCCP (carbonyl cyanide p-trifluoromethoxyphenyIhydrazone), which is a potent mitochondrial uncoupler, on secretion of catecholamines (CA) from the perfused model of the rat adrenal gland and to establish the mechanism of its action. The perfusion of FCCP (3 ${\times}$ $10^{-5}$ M) into an adrenal vein of for 90 min resulted in great increases in CA secretions. Tachyphylaxis to CA-releasing effect of FCCP was not observed by repeated perfusion of it. The CA-releasing effects of FCCP were depressed by pre-treatment with pirenzepine, chlorisondamine, nicardipine, TMB-8, and the perfusion of EGTA plus $Ca^{2+}$-free medium. In the presence of FCCP (3 ${\times}$ $10^{-5}$ M), the CA secretory responses induced by Ach (5.32 ${\times}$ $10^{-3}$ M), and DMPP ($10^{-4}$ M) were significantly enhanced. Furthermore, the perfusion of CCCP (3 ${\times}$ $10^{-5}$ M), a similar mitochondrial uncoupler, into an adrenal vein for 90 min also caused an increased response in CA secretion. Taken together these experimental results indicate that FCCP causes the CA secretion the perfused rat adrenal medulla in a calcium-dependent fashion. It is suggested that this facilitatory effects of FCCP may be mediated by cholinergic receptor stimulation, which is relevant to both stimulation of the $Ca^{2+}$ influx and $Ca^{2+}$ release from cytoplasmic $Ca^{2+}$ stores.

Clinical Implications of the Epidermal Growth Factor Receptor Overexpression in the High-grade Astrocytomas (악성 성상세포종에서 표피성장인자 수용체 과발현의 임상적 의의)

  • Hong Seong Eon;Kang Jin Oh;Lee Hye Kyoung;Yang Moon Ho;Leem Won;Cho Kyung Sam
    • Radiation Oncology Journal
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    • v.14 no.2
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    • pp.87-93
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    • 1996
  • Purpose : To determine the incidence and prognostic effects of EGFR over-expression in the high-grade astrocytomas. Materials and Methods : With 23 paraffin blocks of the high-grade astrocytomas (7 anaplastic astrocytomas and 16 glioblastoma multiforme), expression of EGFR were evaluated by immunohistochemical staining employing polyclonal antibody raised to short cytoplasmic domain of the molecule. Result : Two out of 7 anaplastic astrocytomas and 9 out of 16 glioblastoma multiforme patients showed overexpression of EGFR(p=0.44). Three out of 11 patients of age below 55 and 8 out of 12 patients of age over 54 showed EGFR overexpression(p=0.141). Median survival of the EGFR negative anaplastic astrocytoma patient was 37 months. Median survival of the glioblastoma multiforme Patients were 11 months in EGFR negative group and 7 months in EGFR positive group. But survival difference was not significant (p=0.17). Conclusion There was a marked trend of increasing overexpression of EGFR in older patients. But survival of the glioblastoma multiforme decreased by the overexpression of the EGFR without significant.

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Seven-Year Follow Up of Microscopic Polyangiitis Presenting with Rapidly Progressive Glomerulonephritis (급속 진행성 사구체신염으로 시작된 현미경적 다발성 동맥염(Microscopic Polyangiitis) 환자의 7년간의 장기 추적관찰 1례)

  • Oh, Jin-Won;Kim, Pyung-Kil;Lee, Jae-Seung;Jeong, Hyeon-Joo
    • Childhood Kidney Diseases
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    • v.12 no.1
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    • pp.99-104
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    • 2008
  • Microscopic polyangiitis(MPA) is a systemic necrotizing vasculitis that involves many organ systems including the skin, joint, kidneys, and lungs. In spite of early diagnosis and intensive care, the five-year actuarial patient and kidney survival rates are 65% and 55%. We experienced a case in 7-year-old girl of microscopic polyangiitis presenting with rapidly progressive glomerulonephritis which was confirmed by renal biopsy and positive serum perinuclear antineutrophil cytoplasmic autoantibodies(p-ANCA). The diagnosis of patients first renal biopsy was MPA, p-ANCA-associated crescentic glomerulonephritis. The patients second renal biopsy was done 5 years 6 months later since first renal biopsy, and pathologic diagnosis was chronic sclerosing glomerulonephritis, advanced, due to MPA. We began methylprednisolone pulse therapy, combined with a low dose of cyclophosphamide and plasmapheresis therapy. ACE inhibitor, angiotensin II receptor blocker, and cyclophosphamide were used until now and the patients current age is 14 years old. On admission, the patients laboratory findings showed BUN 117 mg/dL and Cr 2.3 mg/dL, while on the hospital day BUN and Cr values fell to 20.8 mg/dL and 1.6 mg/dL. But renal function was progressed to chronic failure with latest laboratory data BUN 51.7 mg/dL and Cr 3.2 mg/dL. ACE inhibitor, angiotensin II receptor blocker and small dose of immunosuppressant with close observation is the key to maintain the patient survival.

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The Role of the Hydrophobic Group on Ring A of Chalcones in the Inhibition of Interleukin-5

  • Yang, Hyun-Mo;Shin, Hye-Rim;Cho, Soo-Hyun;Song, Gyu-Yong;Lee, In-Jeong;Kim, Mi-Kyeong;Lee, Seung-Ho;Ryu, Jae-Chun;Kim, Young-Soo;Jung, Sang-Hun
    • Archives of Pharmacal Research
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    • v.29 no.11
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    • pp.969-976
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    • 2006
  • Novel chalcones were found as potent inhibitors of interleukin-5 (II-5). 1-(6-Benzyloxy-2-hydroxyphenyl)-3-(4-hydroxyphenyl)propenone (2a, 78.8% inhibition at $50\;{\mu}M,\;IC_{50}=25.3\;{\mu}M$) was initially identified as a potent inhibitor of IL-5. This activity is comparable to that of budesonide or sophoricoside (1a). The benzyloxy group appears to be critical for the enhancement of the IL-5 inhibitory activity. To identify the role of this hydrophobic moiety, cyclohexyloxy (2d), cyclohexylmethoxy (2c), cyclohexylethoxy (2e), cyclohexylpropoxy (2f), 2-methylpropoxy (2g), 3-methylbutoxy (2h), 4-methylpentoxy (2i), and 2-ethylbutoxy (2j) analogs were prepared and tested for their effects on IL-5 bioactivity. Compounds 2c ($IC_{50}=12.6\;{\mu}M$), 2d ($IC_{50}=12.2\;{\mu}M$), and 2i ($IC_{50}=12.3\;{\mu}M$) exhibited the most potent activity. Considering the cLog P values of 2, the alkoxy group contributes to the cell permeability of 2 for the enhancement of activity, rather than playing a role in ligand motif binding to the receptor. The optimum alkoxy group in ring A of 2 should be one that provides the cLog P of 2 in the range of 4.22 to 4.67.

Interleukin-2 Inhibits Secretin-Induced Bile Secretion in Cholangiocytes

  • Ko, Yoo-Seung;Hwang, Seock-Yeon;Park, Jae-Seung
    • Biomedical Science Letters
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    • v.19 no.2
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    • pp.158-163
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    • 2013
  • Cholestatic liver is associated with hepatic inflammation and elevated proinflammatory cytokines. Recent studies indicate that certain cytokines can modulate bile secretion. In the present study, we have examined the role of interleukin (IL-2) on the bile secretion by a combination of study models. To examine the relevance of IL-2 on bile secretion, the expression of IL-2 and IL-2 receptor (IL-2R) of isolated normal and bile duct ligated (BDL) rats cholangiocytes was first measured by RT-PCR. In BDL rats, the expression of IL-2 and IL-2R was significantly increased compared with normal rats. To study the effect of IL-2 on bile secretion, bile flow was measured in normal and BDL rats. At the level of cholangiocytes, secretory responses of isolated bile duct unit (IBDU)s were quantified by videomicroscopy. The administrations of IL-2 had no significant effect on basal bile secretion in normal and BDL rats. There was no significant effect of IL-2 on basal bile ductular secretion as evidenced by no significant difference in luminal area of the IBDUs perfusedwith 100 pM of IL-2 from those of albumin carrier control. However, the secretin-stimulated bile ductular secretion was significantly (P < 0.01) inhibited by $34{\pm}4%$ (normal, n = 12), $21{\pm}5.3%$ (BDL 2 wk, n = 12) and $15{\pm}5.2%$ (BDL 4 wk, n = 12) with the co-administration of IL-2. As with other cytokines, physiologically relevant concentration of IL-2 can significantly inhibit secretin-stimulated bile ductular secretion. These findings support the important roles of cytokines in modulating bile secretion and may contribute to the cholestasis seen in cholestatic liver diseases.

The Therapeutic Effects of Nizatidine in Gastroesophageal Disease with Laryngopharyngeal Reflux Symptoms: Observational Study (위식도 역류성 질환 관련 인후두성 역류(Laryngopharyngeal Reflux : LPR)증상을 호소하는 환자에서의 니자티딘의 치료효과 연구)

  • 노영수;고중화;김광현;김명구;김병국;김성식;김영모;김영훈;김용복
    • Korean Journal of Bronchoesophagology
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    • v.9 no.1
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    • pp.67-74
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    • 2003
  • Larygopharyngeal reflux(LPR) is one form of the Gastroesophageal Reflux Diseases(GERD). It is known to cause various kinds of otolaryngologic symptoms such as hoarseness, globus sensation in throat, chronic throat clearing, and chronic cough, Disease entities diagnosed by otolaryngologists as posterior laryngitis, globus pharyngeus and reflux laryngitis should be suspected as LPR-related diseases. The nizatidine(AXID), as a Histamine H2-receptor antagonist, reduces gastric acid secretion and improves gastric motility function. Objectives : The effect of nizatidine using 150mg b.i.d was evaluated for symptom relief and improvement of laryngoscopic findings in patients with LPR. Materials and Methods : In 30 multicenter, observational trial performed nationalwidely in Korea. 308 patients with LPR symptom were observed to evaluate their symptoms and larygnoscopic findings after 4weeks, 8weeks, 12weeks of treatment with nizatidine. Results : The symptoms of LPR including globus sensation, chronic throat clearing and hoarseness, are reduced significantly after 4 weeks, 8weeks, and 12weeks of treatment(p<0.05). The laryngoscopic findings including diffuse erythema, edema and granulation are improved after nizatidine treatment(p<0.05). and the efficacy of nizatidine on LPR-related sympoms after 4 weeks is 88.6%, and those of after 8 weeks and 12weeks were 92.6%, and 99.1% in ITT(Intent To Treatment) group(p<0.05). And PPA(Per Protocol Analysis)group showed 93.7%, 97.3%, and 99.1% of efficacy after 4, 8, and 12 weeks of nizatidine treatment(p<0.05). Conclusion : These results indicate that in patient with LPR, nizatidine 150mg b.i.d treatment very effectively reduces LPR symptoms and improves laryngoscopic findings as well as reduces gastric acid secretion and improves gastric motility function.

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Inhibitory effects of oroxylin A on endothelial protein C receptor shedding in vitro and in vivo

  • Ku, Sae-Kwang;Han, Min-Su;Lee, Min Young;Lee, You-Mie;Bae, Jong-Sup
    • BMB Reports
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    • v.47 no.6
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    • pp.336-341
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    • 2014
  • Endothelial cell protein C receptor (EPCR) plays important roles in blood coagulation and inflammation. EPCR activity is markedly changed by ectodomain cleavage and release as the soluble EPCR. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-${\alpha}$ converting enzyme (TACE). Oroxylin A (OroA), a major component of Scutellaria baicalensis Georgi, is known to exhibit anti-angiogenic, antiinflammation, and anti-invasive activities. However, little is known about the effects of OroA on EPCR shedding. Data showed that OroA induced potent inhibition of phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and on cecal ligation and puncture (CLP)-induced EPCR shedding through suppression of TACE expression and activity. In addition, treatment with OroA resulted in reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). These results demonstrate the potential of OroA as an anti-sEPCR shedding reagent against PMA and CLP-mediated EPCR shedding.

Inorganic sulfur reduces cell proliferation by inhibiting of $ErbB_2$ and $ErbB_3$ protein and mRNA expression in MDA-MB-231 human breast cancer cells

  • Ha, Ae Wha;Hong, Kyung Hee;Kim, Hee Sun;Kim, Woo Kyoung
    • Nutrition Research and Practice
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    • v.7 no.2
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    • pp.89-95
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    • 2013
  • Dietary inorganic sulfur is the minor component in our diet, but some studies suggested that inorganic sulfur is maybe effective to treat cancer related illness. Therefore, this study aims to examine the effects of inorganic sulfur on cell proliferation and gene expression in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured the absence or presence of various concentrations (12.5, 25, or 50 ${\mu}mol/L$) of inorganic sulfur. Inorganic sulfur significantly decreased proliferation after 72 h of incubation (P < 0.05). The protein expression of $ErbB_2$ and its active form, $pErbB_2$, were significantly reduced at inorganic sulfur concentrations of 50 ${\mu}mol/L$ and greater than 25 ${\mu}mol/L$, respectively (P < 0.05). The mRNA expression of $ErbB_2$ was significantly reduced at an inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05). The protein expression of $ErbB_3$ and its active form, $pErbB_3$, and the mRNA expression of $pErbB_3$ were significantly reduced at inorganic sulfur concentrations greater than 25 ${\mu}mol/L$ (P < 0.05). The protein and mRNA expression of Akt were significantly reduced at an inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05), but pAkt was not affected by inorganic sulfur treatment. The protein and mRNA expression of Bax were significantly increased with the addition of inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05). In conclusion, cell proliferation was suppressed by inorganic sulfur treatment through the ErbB-Akt pathway in MDA-MB-231 cells.

Effects of Repeated Immobilization Stress on the Renal Peripheral Benzodiazepine Receptor in Rats (반복적 부동화 스트레스가 흰쥐 신장의 말초성 benzodiazepine 수용체에 미치는 영향)

  • Park Yong Hoon;Moon Han Ku;Shin Son Moon;Lee Eun Ju;Lee Eun Sil;Ha Jeoung-Hee
    • Childhood Kidney Diseases
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    • v.3 no.1
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    • pp.20-26
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    • 1999
  • Purpose : Several modulatory factors for renal peripheral benzodiazepine receptor (PBR) has been reported, but their physiological significance remains elusive. Tissue-specific, stress-induced down-regulation of renal PBR coupled with the pharmacological stimulation of these effects by angiotensin II suggested that physiological significance of renal PBR may be related to the pathophysiology of stress-induced hypertension. The boderline hypertensive rat (BHR) has been used extensively to study the interaction of environmental factors, such as stress and blood pressure. The BHR is the first-generation progeny of a cross between the spontaneously hypertensive rat and the control Wistar-Kyoto rat. The pathogenesis of stress induced hypertension in this model is not demonstrated well. Methods In this study, BHR (male, 150-200 g) and Sprague-Dawley (SD, male, 150-200 g) rats were treated by repeated immobilization to induce anxiety. We used plus-maze performance to observe the level of anxiety by measuring percent open crosses and percent time in open. Results : Percent open crosses and percent time in open in BHR were lower than in SD rats (P<0.05). Receptor densities of renal PBR in BHRs were significantly lower than those of SDs (P<0.05). We also observed that the renal PBR was upregulated in the repeatedly stressed (immobilization, 2 hours daily, for 2 weeks) rats, both in the BHR and SD. However, the density of renal PBR in the stressed BHR was still lower than that of stressed SD. Renal PBR has been suggested to be an important organs which Is responsible for the production of cholesterol-derived products during stress. Conrlusion : From these results, it can be summarized that the lowed density of renal PBR may be involved in the pathogeneis of stress-induced hypertension.

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