미세절제술과 비교 유전자 보합법에 의한 각종 종양에서의 유전자 변화에 관한 연구

구선회,신소영,임춘화,전영미,이윤이,김진만 충남대학교 의과대학 지역사회의학연구소 2000 충남의대잡지 Vol.27 No.2

For the evaluation of oncogenesis, progression and prognosis of cancer, CGH is an important technique, because this technique is economic due to utilization of only one probe and lack of culture, screening mathod of whole genome and possibility of retrospective and prospective study. By the CGH, genornic variation of 20 breast cancer tissues, 23 stomach cancer tissues and 16 bladder cancer tissues were analyzed. The results were as followes ; 1. breast cancers The CGH results showed gains on chromosomes 8q(40%), lq(30%), 17q(15%), 20q(15%), 18q (15%), 5p(15%), and 13q(15%). The Deletions were on chromosomes 17p(45%) and 22q(20%). High-level amplifications(green/red ratio >1.5) were noted on chromosomes 1p31, iq, 3q25-qter, 5p, 7q31-qter, 8q, 9q22-qter, 10p, l1p, 11q22-qter, 12p, 12q24, 14g21-qter, 15q23-qter, 17q, 18p, 18q12-qter, 20p, and 20q. By comparison with infiltrating ductal carcinoma, the two medullary carcinomas showed high-level amplification on chromosomes iq3l, lq, 8q, 10p, 11p and 12p. 2. stomach cancers 1) Usual amplification sites of genome were lq, 13q, 17q, 20p,q. 2) 17p was the most common deletion site. The other sites of the deletion were lq, 4q. 3) In intestinal type of stomach cancer, genomic variation is more common than diffuse type. 4) In the cases of no evidence of lymph node metastasis, deletion of 17p is absent but amplification of 8q is obvious in the case of lymph node metastasis. 3. bladder cancers Common amplification of copy numbers of DNA sequences by CGH were seen at 1q, 3q, 4q, 5p, 6pq, 7p, 8q, 11q, 12q, 13q, 17q, 18q and 20pq(more than 20% of cases). High level amplification was noted at 1p32, 3p2l, 3q24, 4q26, 8q21-ter, 11q14-22, 12q15-21, 12q21-24, 13q 21-31, 17q22, and 18q22. Deletions were noted at 2q21-qter, 4q13-23, 5q, 8p12-22, 9pq, 11p13-15 (more than 20% of cases).

형광 염색체 In Situ Suppression Hybridization의 임상적 응용에 관한 연구

구선희 충남대학교 의과대학 지역사회의학연구소 1992 충남의대잡지 Vol.19 No.2

A method for chromosome specific staining and its use in clinical cytogenetics is evaluated. Non isotopic fluorescent in situ hybridization provides a fast method for detection of specific nucleic acid sequences. We have used the single color fluorescent in situ hybridization with a α-satellite probe, unique sequence, microdissected probe to investigate the feasibility of simultaneous assessment of numerical and structural chromosome aberrations. When we used the α-satellits probe, Under condition of low stringency, cross hybridization with other subpopulations of the alpohoid family occurs in the whole chromosome and numerous hybridization sites are detected over metaphase. But we could findout the 3 signals in interphase chromosome of Down syndrome we could detect the signals which have been suspicted a deletion point with the unique sequence probe. We could delineate the X-Y translocated region by a microdisscted Y probe. From the above results, it can be a novel method for detection of cytogenetic abnormalities in the clinical cytogenetic field.

Fluorescence in situ Hybridizaton에 의한 염색체 이상의 절단점의 규명

구선회,송인숙 충남대학교 의과대학 지역사회의학연구소 1996 충남의대잡지 Vol.23 No.2

Fluorescence in situ hybrididzation(FISH) is a novel molecular genetic technique. It used for gene mapping in researches and in clinical cytogenetic fields. We perfomed FISH using various kinds of probes for the determination of breakpoints in chromosomal abnormalities. Following results were obtained: 1. Determination of breakpoint in complex translocations. FISH results with chromosome 14/22 centromere probe showed that the breakpoint was 14q11 in the patient with corpus callosum agenesis and complex transocation. 2. Determination of breakpoint of inv(16) in acute myelomonocytic leukemia. FISH results with inv(16) probe showed that the breakpoint was between 16pll and p13 in an abnormal inv(16) chromosome. 3. Determination of breakpoint of dup(17q) in acute myelocytic leukemia. FISH results with iso 17q probe showed that the breakpoint was 17q21 and the duplicated segment from q21-q25. 4. Determination of breakpoint of isodicentric X chromosome. FISH results of Turner syndrome with two iso Xq chromosome using a-satellite X centomere probe showed that the breakpoint was in proxim portion of centromere. From the above results, we could easily find out the breakpoints of chromosomal abnormalities by FISH. It was helpful for the tracing of pathogenesis of genetic disease and cancers.

ATB Expert System을 이용한 항균제 감수성 검사에 관한 연구

구선회 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.2

The success of therapy depends on the selection of antibiotics by the clinician in the case of infection. performance of susceptibility test provides the clinician with a prediction of the activity of an antibiotics. but nowadays resistance mechanisms of increasing complexity are found in a growing number of microbial species. So, for the validation of the antibiotic susceptibility requires the more complete interpretation, using all the knowledge accumulated on antibiotic resistance mechanism. we could detect the resistance mechanism, such as acquire resistance, crossresitance, associated resistance by the ATB expert system which was deviced by artificial knowledge. also we could detect the technical error, incomplete expression of resistance, rare phenotype and impossible phenotype. but there are some limitation for complete adoption in clinical fields because only a few rules were used and not so simple for all members of the microbiology laboratory.

티로파 정(염산티로프라미드 100 mg) 에 대한 안티모딕정의 생물학적 동등성

곽손혁,구선회,린팜두안,강종성,황성주 충남대학교 약학대학 의약품개발연구소 2000 藥學論文集 Vol.16 No.-

Bioequivalence of two tiropramide tablets, test drug (Antimodic® tablet: Chong Kun Dang Pharm. Co.) and reference drug (Tiropa® tablet: Dae Woong Pharm. Co.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty healthy male volunteers were divided randomly into two groups and administered the drug orally at the dose of 100 mg as tiropramide hydrochloride in a 2×2 crossover study. There was a week washout period between administrations. Blood samples were taken at predetermined time intervals for 10 hr and the plasma concentration of tiropramide HCl was determined by a GC/MS method. AUC_0-10hr (area under the plasma concentration-time curve from time zero to 10 hr), C_max (maximum plasma drug concentration) and T_max (time to reach C_max) were estimated from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed no difference in AUC_(0-10hr), C_max and T_max between two products. The apparent differences of these parameters between two products were less than 20% (i.e., 0.043, 6.430 and 8.929% for AUC_(0-10hr), C_max and T_max, respectively). The powers (1-β) for AUC_(0-10hr) and C_max were over 0.9. Minimal detectable differences (Δ) at α=0.05, 1-β=0.8 were less than 20% (i.e. 15.71 and 12.53% for AUC_(0-10hr) and C_max, respectively). The 90% confidence intervals (δ) for these parameters were also within ±20% (i.e. -9.15≤δ≤9.24 and -0.90≤δ≤13.77 for AUC_(0-10hr) and C_max, respectively). These results satisfied the criteria of KFDA guidelines for bioequivalence, indicating the two tablets of tiropramide were bioequivalent.

염색체이상에 관한 연구(611례 분석)

박종우,구선회,민혁기 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.2

From March, 1988 to October, 1993, we studied chromosomal analysis from peripheral blood to investigate chromosomal abnormalities in 611 patients showing multiple congenital anomaly, growth or mental retardation, repeated pregnancy losses, infertility, amenorrhea, pubertal failure, ambiguous genitalia, fetal anormaly, malignant disease and others. 82 chromosomal abnormalities were recognized as follows. 1. The rate of chromosomal abnormality is 13.2%. Among them, autosomal abnormality is 67% and sex chromosomal abnormality is 33%. 2. 22 cases of 47, XY,+21, 21 cases of 47, XX,+21, 3 cases of 46, XX, t(14;21)(qll;qll), and 1 case of 46, XX, t(15;21)(q11;q11) were found in Down syndrome. 3. 13 cases of 45, X, 4 cases of 46X, i(Xq), 2 cases of 46X, i(Xq)/45, X, 1 case of 45, X/46, Xr(X), and 1 case of 45, X/47, XXX were found in Turner syndrome. 4. 6 cases of Kleinfelter syndrome were found. 5. 4 cases of reciprocal translocation, 3 cases of Robertsonian translocation and 2 cases of ring chromosomes were found.

만성 간질환에서 혈청 Type Ⅳ Collagen 측정의 의의

이헌영,김성걸,정현용,구선회,박종우,강대영 충남대학교 의과대학 지역사회의학연구소 1994 충남의대잡지 Vol.21 No.2

To evaluate the clinical significance of serum type N collagen levels in patients with various liver diseases, serum type IV collagen levels were measured by one-step sandwich enzyme immunoassay using monoclonal antibodies in 80 patients from December 1993 to December 1994 at Chung Nam National University Hospital. The results were as follows : 1. Mean age of patients was 45 years. Men was 2.1 times more than women. 2. Compared to 15 normal controls(159.9±34.0 ng/ml), serum type IV collagens were significantly elevated in patients with chronic hepatitis (254.5±158.0 ng/ml), liver cirrhosis(281.0±195.7 ng/ml) and hepatocellular carcinoma(420.5±241.4 ng/ml) (p<0.005). 3. Serum type IV collagen levels were increased without significance in patients with alcholic liver cirrhosis(331.6±244.5 ng/ml) compared to non-alcholic cirrhosis(230.4±117.8 ng/ml. p>0.05). 4. The serum levels of type IV collagen were not correlated with the levels of alanine amino-trnasferase(ALT), aspartate aminotransferase(AST) and alkaline phosphatase(ALP). The results suggest that the serum type IV collagen levels correlate well with the degree of progression of chronic liver diseases. Therefore the measurement of serum type IV collagen is relatively simple and useful method to reflect the progression of chronic liver diseases.

Prognostic implications for gastric carcinoma based on loss of heterozygosity genotypes corrlation with clinicopathologic variables

Koo, Sun Hoe,Jeong, Tae Eun,Kang, Ji Un,Kwon, Kye Chul,Park, Jong Woo,Noh, Seung Moo 충남대학교 형질전환복제돼지연구센터 2004 논문집 Vol. No.8

In this study we used polymorphic DNA markers to examine 38 patients with gastric carcinoma for loss of heterozygosity(LOH) on five chromosomal arms. The aims were to compare LOH genotyping with the clinicopathologic variables and to identify some genetic differences between early (EGC) and advanced gastric carcinoma (AGC). The frequency of LOH was found in 27 of 38(71.1%) cases with a low-level LOH in 17(44.7%) and a high-level LOH(LOH-H) in 10(26.3%). There was statistical significance found in the differentiation of cells{WD/MD vs. PD[well or moderately differentiated vs. poorly differentiated]), metastasis {absent vs. present), and tumor-node-metastasis stage(Ⅰ/Ⅱ vs Ⅲ/Ⅳ) based on LOH genotyping. The frequency of LOH in the markers of chromosome 6 revealed a significant difference between the early and advanced stages(P=0.043). However, there were no differences in each chromosome or in the number of affected chromosomes with an allelic loss between the histologic types EGC and AGC, except for the frequency of the markers on chromosome 22. These findings suggest that LOH genotyping may be another independent prognostic indicator in gastric carcinoma, that LOH-H, particularly the LOH on chromosome6, could be associated with an unfavorable prognosis, while the LOH on chromosome 22 may be related to the histologic progression of gastric carcinoma.

Microsatellite alterations in hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Koo, Sun Hoe,Ihm, Chun Hwa,Kwon, Kye Chul,Lee, Jae Sik,Park, Jong Woo,Kim, Jong Wan 충남대학교 형질전환복제돼지연구센터 2004 논문집 Vol. No.8

A series of 20 hepatocellular carcinomas and 8 intrahepatic cholangiocarcinomas was screened from the Korean population for microsatellite alterations, including a loss of heterozygosity and replication errors using nine microsatellite markers containing several genes. The microsatellite results and our previous comparative genomic hybridization results of two tumors were compared at each locus, and the correlations between these and clinicopathologic variables were examined. The most characteristic findings were found at 13q. Replication errors were prevalent at D13S160 (13q21.2-q3l) and D13S292(13q12). The incidence of loss of heterozygosity, however, was higher at D13S153 (13q14.1~q14.3) and D13S265(13q31~q32). In contrast, there were higher deletion frequencies observed in hepatocellular carcinoma (HCC) and higher amplification frequencies observed in intrahepatic cholangiocarcinoma at 13q in our previous comparative genetic hybridization (CGH) study. Higher frequencies of replication errors were observed at D16S408 (13q12-q2l) and D16S504(13q23~q24) in the HCC This study found that significant differences in the patterns of genetic instability of mjcrosatellites were dependent on the chromosomal loci. It Is believed that certain genes at altered CGH regions, which are relevant to the development and/or progression of these cancers, are activated by different mutation mechanisms.

Application of Fluorescence in situ Hybridization in Clinical Cytogenetics

Koo, Sun Hoe MediMedia Korea 1995 JAMA-Korea Vol.10 No.10