초록 ▼

본 연구에서는 말초혈액세포에서 MDR발현 분율과 MDR단백질의 shift or activation 평가 방법의 표준화를 통하여 난치성 간질환자의 혈액 샘플링 및 분석을 시행하였다. 이를 위하여 다양한 질병진행시기의 간질환자 약물저항성 database (whole genome SNP, 임상 data, 항간질약물사용 data, 병력조사, 약물 농도) database를 제작하였고, intractable patient, monotherapy-responder에서 MDR단백질 발현양, 기능 비교 연구를 시행하였다. 본 연구를 통해서 Epil

본 연구에서는 말초혈액세포에서 MDR발현 분율과 MDR단백질의 shift or activation 평가 방법의 표준화를 통하여 난치성 간질환자의 혈액 샘플링 및 분석을 시행하였다. 이를 위하여 다양한 질병진행시기의 간질환자 약물저항성 database (whole genome SNP, 임상 data, 항간질약물사용 data, 병력조사, 약물 농도) database를 제작하였고, intractable patient, monotherapy-responder에서 MDR단백질 발현양, 기능 비교 연구를 시행하였다. 본 연구를 통해서 Epilepsy 환자에서는 MDR basal expression이 증가하고, Frequent seizure를 가지는 intractable patient에서 PGP basal expression이 더욱 증가함을 확인하였고, Multiple AED사용은 PGP 기능의 증가를 가져올 수 있음을 알았다. 결론적으로 PBMNCs을 이용한 PGP 발현분석은 MDR status를 반영할 수 있는 가능성을 제시하였다.

Abstract ▼

About one third of epilepsy patients become refractory despite the adequate medical treatment. One possible cause of the refractoriness is the multidrug resistance mechanism. P-glycoprotein, also known as multidrug resistance protein-1 (MDR1), is reported as the major multidrug resistance protein th

About one third of epilepsy patients become refractory despite the adequate medical treatment. One possible cause of the refractoriness is the multidrug resistance mechanism. P-glycoprotein, also known as multidrug resistance protein-1 (MDR1), is reported as the major multidrug resistance protein that mediates the drug efflux and contributing factor for refractoriness of epilepsy. MDR1 could be the marker for predicting treatment outcome of intractable epilepsy. Since peripheral blood mononuclear cells (PBMNCs) also express MDR1, we investigated MDR1 status of PBMNCs by flow cytometry and analyzed with various clinical parameters including seizure frequency and medication number.
Clinical and MDR1 data were collected from 117 epilepsy patients. PBMNCs were treated with vinblastine or DMSO and then incubated with MDR1 antibody for MDR1 shift assay. MDR1 activity (vinblastine treated) and expression (DMSO treated) level was obtained by flow cytometry. Expression level represents basal expression condition of MDR1 and activity level reflects MDR1' s actual reactivity to substrates in PBMNCs. The various clinical variables were analyzed in comparison to MDR1 stats. The enrolled patients (37.8 ± 10.8 years old) had 1.7 ± 4.5 seizures per week and took 2.8 ± 1.3 antiepileptic drugs (AEDs). We evaluated the refractoriness of patients according to seizure frequency (≥1 seizures per week vs. <1) and AED numbers required to control seizures (>2 AEDs vs. ≤2). High seizure frequency group expressed more MDR1 in PBMNCs compared to low frequency group (p=0.009). High medication number group showed high MDR1 activity level compared to low number group (p=0.028). Multiple logistic regression analysis data showed that both MDR1 expression and activity were independent predictors of seizure frequency and required medication number, respectively. Our data suggest that MDR1 profile of PBMNCs would be a potential biomarker for predicting treatment outcome of intractable epilepsy.

목차 Contents

• 1. 표지 ...1
• 2. 제출문 ...3
• 3. 보고서 요약서 ...4
• 4. 요약문(한글) ...5
• 5. 요약문(영문) ...6
• 6. 연구 성과 실적 및 향후 계획 ...7
• 7. 참여연구원 현황표 ...11
• II. 총괄연구과제 연구결과 ...12
• 1. 연구개발과제의 배경 및 필요성 ...13
• 2. 국내외 기술개발 현황 ...15
• 3. 연구개발과제의 추진체계 ...18
• 4. 연구개발수행 내용 및 결과 ...19
• 5. 목표달성도 및 관련분야 기여도 ...23
• 6. 향후 연구성과 추진 계획 ...24
• 7. 연구개발결과의 파급효과 ...24
• 8. 연구개발결과의 활용계획 ...25
• 9. 연구개발과정에서 수집한 해외과학기술정보 ...25
• IV. 첨부서류 ...26
• 목차 ...27
• 1. 자체평가의견서 ...27
• 2. 실적 증빙자료 ...31
• 3. 기타 첨부서류 ...31