• Journal of Preventive Medicine and Public Health
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• 제31권2호
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• pp.275-284
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• 1998

1996년 3월부터 1996년 12월까지 충북대학교병원 비뇨기과에 입원하여 치료를 받은 방광암 환자 67명과 암 아닌 다른 질환을 가진 대조군 67명을 대상으로 흡연, 음주, 직업력 등을 포함한 생활 습관과 NAT2와 GSTM1, 그리고 GSTT1 유전자 다형성 양상을 조사하여 다음과 같은 결론을 얻었다. 1. NAT2 다형성 분포는, 환자군이 slow, intermediate, rapid acetylator가 각각 3.0%, 38.8%, 58.2%, 그리고 대조군이 7.6%, 40.9%, 51.5%였으며, NAT2의 활성과 방광암 위험도 사이의 관련성은 유의하지 않았다($\chi^2_{trend}=1.18$, P-value>0.05). 2. GSTM1 결손은 환자군의 68.7%, 대조군의 49.3%에서 확인되었으며, OR(95% 신뢰구간)이 2.23(1.12-4.56)으로, 방광암 발생의 위험인자로 나타났다. 3. GSTT1은 환자군의 26.9%,그리고 대조군의 43.3%에서 결손이 있는 것으로 나타나서, GSTT1 결손은 방광암에 대하여 보호효과가 있는 것으로 관찰되었다(OR: 0.48, 95% 신뢰구간: 0.23-0.99). 4. 흡연 여부는 방광암의 발생에 유의한 영향을 미치지 않는 것으로 나타났는데(OR=1.85, 95% CI: 0.85-4.03), 이는 환자군과 대조군의 흡연률이 모두 높기 때문으로 판단된다. 5. 그 외, 음주력, 직업력, 수혈 여부, 그리고 피임시술의 과거력 등의 요인들은 방광암 발생과 유의한 관련성이 없는 것으로 나타났다.

• 미생물학회지
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• 제28권1호
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• pp.35-40
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• 1990

Thiostrepton 내성 유전자(tsr)를 포함하는 multi-copy 재조합 플라스미드 pJY7J2의 제한효소 절단지도를 작성하였다. pJY, 712는 Streptomyces에서 넓은 host range를 나타내었으며 cloning 목적에 사용할 수 있는 단일 BgtIl 제한효소 인식부위를 갖고 있었다. 플라스미드 pJY 712는 lethal zygosis(Ltz+) 현상을 보였다. pJY 712의 혁질전환빈도는 S. lividans에서 $5.0\times 10^{4}$ TFU였다. pJY 712의 Bell 제한효소 인식부위에 tyrosmase 유전자(mel)를 삽입하여 플라스미드 PJY713을 제조하였다. met 유전자를 포함한 재조합 플라스미드 pJY 714는 pJY 713의 일부분(1.9kb BgllI-BelI 단편)을 제거하여 제고하였다.

• BMB Reports
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• 제43권10호
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• pp.693-697
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• 2010

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome characterized by predisposition to early-onset cancers. HNPCC is caused by heterozygous loss-of-function mutations within the mismatch repair genes MLH1, MSH2, MSH6, PMS1, and PMS2. We genotyped the MLH1 and MSH2 genes in patients suffering from Lynch syndrome and in 11 unrelated patients who were diagnosed with colorectal cancer and had subsequently undergone surgery. Five Lynch syndrome patients carried germline mutations in MLH1 or MSH2. Two of these were identified as known mutations in MLH1: deletion of exon 10 and a point mutation (V384D). The remaining three patients exhibited novel mutations: a duplication (937_942dupGAAGTT) in MLH1; deletion of exons 8, 9, and 10; and a point mutation in MLH1 (F396I) combined with multiple missense mutations in MSH2 (D295G, K808E, Q855P, and I884T). The findings underline the importance of efficient pre-screening of conspicuous cases.

• 대한화학회지
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• 제48권1호
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• pp.33-38
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• 2004

두경부 편평 세포암종(HNSCC: head and neck squamous cell carcinoma) 의 발생과 관련하여 p53 종양 억제 유전자 (tumor suppressor gene) 의 돌연변이는 높은 비율로 나타나는 것으로 보고 되고 있다. 단국대학교 병원에서 두경부 종양으로 진단 받고 수술 받은 환자의 조직 50개를 대상으로 p53 종양 억제 유전자의 exon 5-8 까지의 영역에서 DNA를 추출하여 PCR-SSCP(polymerase chain reaction single strand conformational polymorphism) 방법과 DHPLC(denaturing high performance liquid chromatography) 방법으로 p53체세포 돌연변이(somatic mutation)를 비교 분석하였다. 그 결과 SSCP 분석 방법은 16개(32%), DHPLC 분석 방법은 17개(34%) 를 검출하였고 그 중 SSCP와 DHPLC 분석 방법 모두 exon 8번에서 결실(deletion) 형태의 돌연변이를 확인하였으며 최종적으로 자동 염기 서열 분석기(automatic DNA sequencer) 를 통하여 모든 돌연변이를 확인하였다. DHPLC 분석방법이 SSCP 방법보다 분석 시간이나 노력이 덜 소모되며 보다 더 정확한 돌연변이 검출 방법임을 확인하였다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제42권6호
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• pp.337-344
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• 2016

Objectives: The purpose of this study was to evaluate the anti-cancer activity of cisplatin by studying its effects on cell viability and identifying the mechanisms underlying the induction of cell cycle arrest and apoptosis on oral squamous cell carcinoma (OSCC) cell lines with varying p53 mutation status. Materials and Methods: Three OSCC cell lines, YD-8 (p53 point mutation), YD-9 (p53 wild type), and YD-38 (p53 deletion) were used. To determine the cytotoxic effect of cisplatin, MTS assay was performed. The cell cycle alteration and apoptosis were analyzed using flow cytometry. Western blot analysis was used to detect the expression of cell cycle alteration- or apoptosis-related proteins as well as p53. Results: Cisplatin showed a time- and dose-dependent anti-proliferative effect in all cell lines. Cisplatin induced G2/M cell accumulation in the three cell lines after treatment with 0.5 and $1.0{\mu}g/mL$ of cisplatin for 48 hours. The proportion of annexin V-FITC-stained cells increased following treatment with cisplatin. The apoptotic proportion was lower in the YD-38 cell line than in the YD-9 or YD-8 cell lines. Also, immunoblotting analysis indicated that p53 and p21 were detected only in YD-8 and YD-9 cell lines after cisplatin treatment. Conclusion: In this study, cisplatin showed anti-cancer effects via G2/M phase arrest and apoptosis, with some difference among OSCC cell lines. The mutation status of p53 might have influenced the difference observed among cell lines. Further studies on p53 mutation status are needed to understand the biological behavior and characteristics of OSCCs and to establish appropriate treatment.

• 생명과학회지
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• 제19권1호
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• pp.1-8
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• 2009

본 연구에서는 monofunctional alkylating agent인 N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) 에 의한 인체 백혈병 U937 세포의 증식억제에 관한 기전 확인하였다. MNNG에 의한 U937 세포의 증식억제는 세포주기 G2/M arrest 및 apoptosis 유방과 연관이 있었으며, MNNG 는 G2/M기 조절에 관여하는 주요 cyclin 및 Cdk들의 발현 수준에는 큰 영향이 없었으나 cyclin B1 및 Cdk2-associated kinase의 활성을 매우 저하시켰다. MNNG 처리로 Cdk inhibit p2l(WAF1/CIP1)이 전사 및 번역 수준에서 발연이 증가되었으며, p21 promoter 의 활성도 증가되었다. p21 promoter deletion constructs을 이용한 연구에서 MNNG의 responsive element 부위는 전사 개시 부위 113-61 부근임을 확인하였다. 이 결과들은 MNNG에 의한 cyclin/Cdk 복합체의 kinase 활성 저하가 p53 비의존적인 p21의 활성 증가에 기인한 것임을 보여주는 것이며, 이는 MNNG의 암세포에서의 항암기전을 이해하는 귀중한 자료로서 제공될 것으로 기대된다.

• Journal of Microbiology and Biotechnology
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• 제23권10호
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• pp.1454-1459
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• 2013

The changes in prodiginines productions caused by pH shock culture of Streptomyces coelicolor strains were estimated. In Streptomyces coelicolor M511, undecylprodiginine and streptorubin B productions increased 1.8-fold (37.22 mg/g) and 2.5-fold (18.61 mg/g), respectively, by pH shock (from 7.2 to 4.0). In contrast, this resulted in the significantly decreased prodigignines production in the redP deletion mutant SJM1; 3.7-fold for undecylprodiginine, 4.4-fold for streptorubin B, 5.2-fold for methylundecylprodiginine, and 6.4-fold for methyldodecylundecylprodiginine, respectively. RT-PCR analyses showed that, during pH shock, expression of redD, the transcription activator gene, was increased while the expression of fabH, the decarboxylative condensation enzyme gene in fatty acid biosynthesis, was decreased in both strains. The enhanced redD expression was in good accordance with the increased total prodiginines production of M511. However, for SJM1 mutant, the decrease of fabH expression occurred more strikingly, such that it became almost completely turned off during acidic pH shock culture. Therefore, a down-regulation of fabH was considered to be the cause of decreased amount of total prodiginines produced, although redD expression was high in SJM1 mutant.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3825-3827
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• 2012

FISH is one of the most sensitive molecular methods to detect genetic abnormalities with DNA probes. When cytogenetic studies are normal or insufficient, FISH may detect cryptic rearrangements, rare or slowly proliferative abnormal populations in non-mitotic cells. We cytogenetically evaluated 70 childhood ALL - 67.1% were found to have an abnormal karyotype. The 23 patients (32.9%) with a normal karyotype were analyzed by FISH applying two probes; TEL/AML1 and MYB which detect cryptic rearrangements of t(12;21)(p13;q22) and deletion of (6q) respectively, associated with a good prognosis. Out of 23 patients, one was positive for t(12;21)(p13;q22) (4.3%). None of our patients were positive for MYB del(6q). Two patients showed an extra signal for MYB on chromosomes other than 6 (8.6 %) indicating amplification or duplication. Findings were compared with the available literature. Our study clearly indicated the integrated FISH screening method to increase the abnormality detection rate in a narrow range. FISH is less useful for diagnostic study of patients with suspected del(6q) but it helps in detecting known cryptic rearrangements as well as identification of new abnormalities(translocation , duplication and amplification) at the gene level.

• 식품기술
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• 제8권4호
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• pp.179-191
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• 1995

Thermoanaerobacter ethanolicus유래 thermophilic amylopullulanase의 thermophilicity와 thermostability의 기작을 규명하기 위하여 N-말단과 C-말단으로부터 nested deletion mutatnt와 sitedirected mutagenesis등에 의한 변이효소를 제조, 분석하였다. 이러한 까다로운 변이효소를 제조하여 amylopullulanase의 특정부위가 효소의 thermophilicity와 thermostability에 관여하고 있는 것을 확인했다. N-말단의 start amino acid에서 194와 324 아미노산잔기에 이르는 부위 (TPR)가 이 효소의 높은 최적반응온도의 유지에 관련되어 있고 1102와 1224잔기에 이르는 부위 (TSR)는 thermodenaturation이 잘 일어나지 않도록 하고 있었다. 야생형 amylopullulanase (Apu), 변이효소중 ApuN342와 ApuN106/C379는 비슷한 효소비활성과 Km값을 가지고 있었다. TPR부위의 site-directed mutagenesis에 의한 변이효소중 P240A (proline$\rightarrow$alanine), P244A, P240A-P244A는 야생형의 최적반응온도 $80^{\circ}C$와 똑같았지만 효소의 열안전성(반감기)는 $85^{\circ}C$에서 21, 105, 128분을 보여 주었다. TSR에서의 변이효소중 P1159A, P1202A는 열안전성은 비슷하였지만 반응최적온도는 $85^{\circ}C$와 $90^{\circ}C$로 야생형 Apu보다 오히려 높아졌다. 따라서 proline은 분자내에서 thermophilicity와 thermostability를 항상 증가시키는 쪽으로 영향을 주지 않는 것으로 보인다. Proline은 그 위치와 주위의 다른 아미노산잔기와 같이 종합적으로 분자의 구조에 영향을 미치고 있는 것으로 판단된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3305-3311
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• 2012

Background: The present study aimed to find the prognostic implications of two polymorphisms in TP53 (p.R72P, PIN3 Ins16bp) and one in CCR5 ($CCR5{\Delta}32$) in sporadic breast cancer patients. Methods: DNA samples of 80 breast cancer patients and 80 age and gender matched unrelated healthy control individuals from Punjab, North West India were analyzed. Results: For p.R72P, the genotype frequency was 13.8% (RR), 58.8% (RP), 27.5% (PP) in patients and 33.9% (RR), 40.0% (RP), 26.5% (PP) in controls. For PIN3 Ins16bp, the genotype frequencies were 53.75% (A1A1), 37.5% (A1A2), 8.75% (A2A2) in patients and 66.3% (A1A1), 31.3% (A1A2), 2.5% (A2A2) in controls. Only 4 (5%) breast cancer patients were heterozygous for $CCR5{\Delta}32$ deletion. Common RR-A1A1-WT/WT genotype was lower while RP-A1A2-WT/WT genotype was higher in patients as compared to controls. RP-A1A1-WT/WT genotype was significantly higher in patients as compared to control individuals (p = 0.008). Conclusion: Though a clear association of any particular genotype with sporadic breast cancer or stage was not apparent, the results of present study were suggestive that sporadic breast cancer patients with RR-A1A1-WT/WT genotype might have a better response to chemotherapy, thus improving their chances of survival.