Diagnostic significance of serum HMGB1 in colorectal carcinomas

High mobility group box 1 protein (HMGB1), a nuclear protein, can be translocated to the cytoplasm and secreted in colon cancer cells. However, the diagnostic significance of HMGB1 has not been evaluated in colorectal carcinomas. For this purpose, we have screened the expression and secretion of HMGB1 in 10 colon cancer cell lines and 1 control cell line and found that HMGB1 was detected in the culture medium. To evaluate the diagnostic value of HMGB1, we performed an enzyme-linked immunosorbent assay to measure HMGB1 levels and compared them to carcinoembryonic antigen (CEA) levels in the serum samples of 219 colorectal carcinoma patients and 75 healthy control subjects. We found that the serum HMGB1 level was increased by 1.5-fold in patients with colorectal carcinoma compared to those in healthy controls. When HMGB1 and CEA levels were compared, HMGB1 had similar efficacy as CEA regarding cancer detection (the sensitivity was 20.1% for HMGB1 vs. 25.6% for CEA, and the specificity was 96% for HMGB1 vs. 90.7% for CEA). Moreover, the diagnostic accuracy of HMGB1 for stage I cancer was significantly higher than that of CEA (sensitivity: 41.2% vs. 5.9%; specificity: 96% vs. 90.7). When we combined HMGB1 and CEA, the overall diagnostic sensitivity was higher than that of CEA alone (42% vs. 25.6%), and the diagnostic sensitivity for stage I was also elevated (47% vs. 5.9%). However, the prognosis of patients was not related with serum HMGB1 concentrations. Our findings indicate that serum HMGB1 levels are increased in a subset of colorectal carcinomas, suggesting their potential utility as a supportive diagnostic marker for colorectal carcinomas.ope

조기 종결 코돈을 가진 비정상적인 유전자들의 발현 조절에 hypoxia가 미치는 영향 규명

Dept. of Medical Science/석사mRNAs containing premature termination codon (PTC) are generally degraded by the nonsense-mediated mRNA decay (NMD) pathway, a well-known RNA surveillance mechanism. PTCs are generated by nonsense or frameshift mutation at coding mononucleotide repeats (cMNR) in high microsatellite instability (MSI-H) colon cancers. These PTC-containing abnormal mRNAs are identified as relevant substrates of NMD, and therefore suspected to be putative tumor target genes. Although aberrant mRNAs are degraded by NMD, this NMD has also been inhibited in several conditions. Hypoxia is one of the NMD inhibiting conditions and common in many tumors, especially in the tumor cells located at the center.In this study, the effect of hypoxic change in the genes containing PTC was characterized through mimicking the tumor microenvironment. It was firstly confirmed that NMD was inhibited in hypoxic conditions using mutant β-globin genes. Then, PTC-containing mRNAs were selected by analyzing the status of frameshift mutations in 5 MSI colon cancer cell lines. 19 PTC-containing mRNAs were profiled by quantitative RT-PCR in 5 MSI-H colon cancer cell lines. Hypoxia exposure and treating hypoxic mimetic drugs in vitro were utilized. Specifically, highly up-regulated targets, RAPGEF6, TBC1D23, SPAG9, HDAC2, SLC35F5, and SMG7, in hypoxic conditions might affect tumor progression. This characterization of PTC-containing genes in hypoxic effects might give clues to the biological effect of NMD in vivo, and play a role in tumor progressionope

WTO體制下의 貿易紛爭解決節次 : 紛爭解決規則 및 節次에 관한 諒解覺書를 중심으로

학위논문(석사)--서울大學校 大學院 :法學科 國際法專攻,1995.Maste

Preparation and Characterization of Electroactive Ethylene Imine-modified Polyurethane

학위논문(석사)--서울대학교 대학원 :바이오시스템.소재학부(바이오소재공학전공),2009.2.학위논문(석사) -