초록

Ⅲ. 연구개발의 내용 및 범위
본 연구에서는 암모델마우스를 이용하여 암관련 오토항체생성 B세포군을 확보하고 이로부터 암관련 오토항체를 개별적으로 분석하여 혈중오토항체 검출법을 제안하고자 하였다. 우선은 암 발생 마우스에 유도되는 암유래 오토항체들의 특이반응 항원특성을 조사하여 임상적 타당성을 확보하고자 하였고, 오토항체 반응 에피토프군을 펩타이드 라이브러리 스크리닝으로 도출하여 오토항체 검출법을 제안하였다.

Abstract ▼

An ideal cancer marker would allow a simple blood test to detect cancer and its level would correlate with the stage of tumor progression. Currently available serum markers are based on the measurement of tumor antigens. However, no single has
been recognized as a true cancer marker due to the la

An ideal cancer marker would allow a simple blood test to detect cancer and its level would correlate with the stage of tumor progression. Currently available serum markers are based on the measurement of tumor antigens. However, no single has
been recognized as a true cancer marker due to the lack of sensitivity and specificity. To overcome these limitations of tumor antigens, there are alternative attempts for the cancer biomarker development based on the detection of autoantibodies against tumor antigens in patients' sera. Compared to serum-derived proteins, antibodies in serum are stable, highly specific and readily detected with well-validated secondary reagents, making them ideal for diagnosis.
To identify tumor-associated autoantibodies in hepatocellular carcinoma (HCC), we used spleen cells derived from HCC model mouse (HBx or H-ras12V transgenic mouse). The spleen cells from HCC model mouse were fused with myeloma cells and stable hybridoma clones producing antibodies reactive to hepatocellular carcinoma cells were selected. The rationale of model mouse-derived autoantibodies for the study of human tumor-associated autoantibodies was obtained by analyzing their reactivity of to human tumor cells. We also identifed the target antigens directed to these autoantibodies by proteomic techniques and screening their mimotopes from random cyclic peptide phage display library. Based on these results, we set up ELISA for analyzing human sera to diagonise cancer using mimotope phages, such as K1p7, K94p1 and XC154p1. K1p7
phage ELISA is highly effective to diagonise hepatocellularcarcinoma (sensitivity 96.5%, specificity 100%). XC154p1 phage ELISA is also effective to diagonise HCC (sensitivity 86.96%, specificity 88.24%). Interestinly, although K94 autoantibody was prepared from HCC model mouse, K94p1 phage ELISA is not effective for diagnosis of HCC but useful for diagonosis of breast cancer. K94p1 phage ELISA can diagonize breast cancer with sensitivity of 50% and specificity of 82.61%. Also we analysed patients sera using commercial AFP detection kit and simultaneous quantification of XC154 autoantibody plus AFP was performed. A logistic regression-based XC154+AFP index enhanced sensitivities and specificities over AFP or XC154 alone in distinguishing hepatocellular carcinoma from nonmalignant cases, which may confer a novel platform for the diagnosis of liver cancer.

목차 Contents

• 표지 ... 1
• 제출문 ... 2
• 보고서 초록 ... 3
• 요약문 ... 4
• SUMMARY ... 6
• CONTENTS ... 7
• 목차 ... 8
• 제 1 장 연구개발과제의 개요 ... 9
• 제 1절 연구개발의 목적 ... 9
• 제 2절 연구개발의 필요성 ... 9
• 제 3 절 연구개발의 범위 ... 12
• 제 2 장 국내외 기술개발 현황 ... 14
• 제 1 절 국내외 관련분야 기술개발현황 ... 14
• 제 2 절 본 연구결과가 국내외 기술개발 현황에서 차지하는 위치 ... 14
• 제 3 장 연구개발 수행 내용 및 결과 ... 16
• 제 1 절 이론적, 실험적 접근방법 ... 16
• 제 2 절 연구내용 (methods) ... 18
• 제 3 절 연구결과 (Results and Discussion) ... 24
• 제 4 장 목표달성도 및 관련분야에의 기여도 ... 72
• 1. 목표달성도 ... 72
• 2. 관련분야에의 기여도 ... 72
• 제 5 장 연구개발결과의 활용계획 ... 73
• 제 6 장 연구과정에서 수집한 해외과학기술정보 ... 74
• 제 7 장 참고문헌 ... 77