• Biomedical Science Letters
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• v.11 no.4
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• pp.421-427
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• 2005

To evaluate the diagnostic significance of p16 overexpression in human hepatocellular carcinoma (HCC), we analyzed p16 status and growth inhibitory patterns by p16 overexpression in HCC cell lines having different pRE status. SKHep1 and SNU449 cells show homozygous deletion of p16. The p16 gene in SNU398 cell is inactivated at posttranscription level. Adenovira1-p16 (Ad-p16) infection inhibits the cell growth in Hep3B, SNU398, and SNU449. Failure of growth inhibition in SKHepl results from the low transduction efficiency of adenovirus. The p16-mediated growth inhibition shows G 1 phase arrest in pRE-positive SNU449 but not in pRE-negative Hep3B. These results suggest that therapeutic efficacy of p16 gene might be considered on the transduction efficiency and the toxicity of adenoviral vector. Beside, growth inhibitory effect of p16 could be exerted through either pRE-dependent or -independent pathway.

• Journal of Microbiology and Biotechnology
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• v.11 no.4
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• pp.724-726
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• 2001

The growth of baceriophage T4 is inhibited by the presence of the tin gene product o bacteriophage P2. The interaction between purified Tin and gp32 proteins was observed using coimmunoprecipitation experiments. The in vivo interaction was confirmed by yeast two-hybrid experiments. A deletion analysis showed that the Asp 163 region of gp32 to DNA substrates was not affected by the presence of Tin, Thus, it would appear that the inhibition of 4 growth by Tin was due to a protein-protein interaction rather than affecting the DNA-binding ability of gp32.

• Proceedings of the Zoological Society Korea Conference
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• 1998.10b
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• pp.113-113
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• 1998

In Saccharomyces cerevisiae UV irradiation and a variety of chemical DNA -damaging agents induce the transcription of specific genes, including several involved in DNA repair. One of the best characterized of DNA -damage inducible genes is PHRI, which encodes the apoenzyme for DNA photolyase. Basal-level and damage-induced expression of PHRI require an upstream activation sequence, UASPHRI. Here we report the identification of the UlvIE6 gene of S. cerevisiae as a regulator of UASPHRl activity. Surprisingly, the effect of deletion of UME6 is growth phase dependent. In wild-type cells PHRI is induced in late exponential phase, concomitant with the initiation of glycogen accumulation that precedes the diauxic shift. Deletion of UNIE6 abolishes this induction, decreases the steady-state concentration of photolyase molecules and PHRI mRNA, and increases the UV sensitivity of a rad2 mutant. The results suggest that UM E6 contributes to the regulated expression of a subset of damage-responsive genes in yeast. Furthermore, the upstream repression sequence, URSPHRI, is required for repression and damage-induced expression of PHRl. Here we show identification of YER169W and YDR096W as putative regulators acting through $URS_{PHRI}$. These open reading frames were designated as RPHI (YERl69W) and RPH2 (YDR096W) indicating regulator of PHRI. Simultaneous disruption of both genes showed a synergistic effect, producing a four-fold increase in basal level expression and a similar decrease m the induction ratio following treatment of methyl methanesulfonate(MMS). Mutation of the sequence ($AG_4$) bound by Rphlp rendered the promoter of PHRI insensitive to changes in RPHI or RPH2 status. The data suggest that RPHI and RPH2 act as damage-responsive negative regulators of PHRI. Surprisingly, the sequence bound by Rphlp in vitro is found to be $AG_4$ which is identical to the consensus binding site for the regulators Msn2p and Msn4p involved in stress-induced expression. Deletion of MSN2 and MSN4 has little effect on the induction$.$ ratio following DNA damage. However, all deletions led to a significant decrease in basal-level and induced expression of PHRI. These results imply that MSN2 and MSN4 are positive regulators of P HRI but are not required for DNA damage repression. [Supported by grant from NIH]om NIH]

• Journal of Preventive Medicine and Public Health
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• v.31 no.2 s.61
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• pp.275-284
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• 1998

Activities of enzymes involved in the metabolism of various carcinogenic xenobiotics is one of the most important host factors for cancer occurrence. N-acetyltransferase (NAT) and glutathione S-transferases (GST) are enzymes which .educe the toxicity of activated carcinogenic metabolites. Slow N-acetylation and lack of GST mu (GSTMI) were reported as risk factors of bladder cancer. GST theta (GSTT1), which is another type of GST, was reported to be deleted at higher proportion among Koreans. Since cause of bladder cancer is not fully explained by single risk factor, many kinds of enzymes would be involved in the metabolism of carcinogens excreted in urine. This study was performed to investigate whether the polymorphisms of NAT2, GSTM1 and GSTT1 are risk factors of bladder cancer and to evaluate the effects of their interaction on bladder cancer development. Sixty-seven bladder cancer and 67 age- and sex-matched non-cancer patients hospitalized in Chungbuk National University Hospital from March to December 1996, are the subjects of this case-control study. Questionnaire interview was done and the genotypes of NAT2, GSTM1 and GSTT1 were identified using PCR methods with DNA extracted from venous blood. The effects of the polymorphism of NAT2 and GSTM1 and their interaction on bladder cancer were statistically tested after controlling the other risk factors. The frequencies of slow, intermediate, and rapid acetylators were 3.0%, 38.8%, and 58.2% to. the cases, and 7.6%, 40.9%, and 51.5% for the controls, respectively. The risk of bladder cancer was not associated with the increase of NAT2 activity($\chi^2_{trend}=1.18$, P-value>0.05). GSTM1 was deleted in 68.7% of the cases and 49.3% of the controls ($\chi^2=5.21$, P-value<0.05), and the odds ratio (95% CI) was 2.23 (1.12 - 4.56). GSTT1 deletion, the .ate of which were 26.9% for the bladder cancer patients and 43.3% for the controls, was a significant protective factor against bladder cancer. Smoking history turned out to be insignificant as a risk factor of bladder cancer (OR=1.85, 95% CI: 0.85 - 4.03), and occupation could not be tested because of the extremely small number of occupational history related to the increase of bladder cancer. In multiple logistic analysis controlling the effects of other risk factors, GSTM1 deletion was the only significant risk factor for bladder cancer (OR: 2.56, 95% CI: 1.22-5.36, P-value<0.05), but slow acetylation and GSTT1 deletion were not. These results suggest that GSTM1 deletion may be a significant risk factor of bladder cancer. Since there have been much debates on causal relationship between slow acetylation and GSTT1 deletion, and bladder cancer, further studies are needed.

• Journal of Genetic Medicine
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• v.18 no.1
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• pp.31-37
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• 2021

Purpose: To summarize the results of chromosomal microarray analysis (CMA) for copy number variants (CNVs) detection and clinical utility in a single tertiary hospital. Materials and Methods: We performed CMA in 46 patients over the course of two years. Detected CNVs were classified into five categories according to the American College of Medical Genetics and Genomics guidelines and correlated with clinical manifestations. Results: A total of 31 CNVs were detected in 19 patients, with a median CNV number per patient of two CNVs. Among these, 16 CNVs were classified as pathogenic (n=3) or likely pathogenic (LP) (n=11) or variant of uncertain significance (n=4). The 16p11.2 deletion and 16p13.11 deletion classified as LP were most often detected in 6.5% (3/46), retrospectively. CMA diagnostic yield was 24.3% (9/37 patients) for symptomatic patients. The CNVs results of the commercial newborn screening test using next generation sequencing platforms showed high concordance with CMA results. Conclusion: CMA seems useful as a first-tier test for developmental delay with or without congenital anomalies. However, the classification and interpretation of CMA still remained a challenge. Further research is needed for evidence-based interpretation.

• Bulletin of the Korean Chemical Society
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• v.20 no.9
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• pp.1078-1084
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• 1999

A synthetic cecropin A(1-13)-melittin(1-13) [CA-ME] hybrid peptide was known to be an antimicrobial peptide having strong antibacterial, antifungal and antitumor activity with minimal cytotoxic effect against human erythrocyte. Analogues were synthesized to investigate the influences of the flexible hinge region of CA-ME on the antibiotic activity. Antibiotic activity of the peptides was measured by the growth inhibition against bac-terial, fungal and tumor cells and vesicle-aggregating or disrupting activity. The deletion of Gln-Gly-Ile (P1) or Gly-Gln-Gly-Ile-Gly (P3) from CA-ME brought about a significant decrease on the antibiotic activities. In contrast, Gly-Ile-Gly deletion (P2) from CA-ME or Pro insertion (P5) instead of Gly-Gln-Gly-Ile-Gly of CA-ME retained antibiotic activity. This result indicated that the flexible hinge or β-bend structure provided by Gly-Gln-Gly-Ile-Gly, Gln-Gly, or Pro in the central region of the peptides is requisite for its effective antibiotic activity and may facilitate easily the hydrophobic C-terminal region of the peptide to penetrate the lipid bilayers of the target cell membrane. In contrast, P4 and P6 with Gly-Gln-Gly-Pro-Gly or Gly-Gln-Pro in the central region of the peptide caused a drastic reduction on the antibiotic activities. This result suggested that the con-secutive β-bend structure provided by Gly-Gln-Gly-Pro-Gly or Gly-Gln-Pro in the central hinge region of the peptide seems to interrupt the ion channel/pore formation on the target cell membranes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4057-4059
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• 2013

Background: Fluorescence in situ hybridization (FISH) testing may be useful to screen for bladder carcinoma or dysplasia by detecting aneuploidy chromosomes 3, 7, 17 and deletion of the chromosome 9p21 locus in urine specimens. This study aimed to assess the sensitivity, specificity, positive and negative predictive value of FISH in a multi-ethnic population in Asia. Materials and Methods: Patients with haematuria and/or past history of urothelial cancer on follow-up had their voided urine tested with FISH. Patients then underwent cystoscopy/ureteroscopy and any lesions seen were biopsied. The histopathological reports of the bladder or ureteroscopic mucosal biopsies were then compared with the FISH test results. Results: Two hundred sixty patients were recruited. The sensitivity and specificity of the FISH test was 89.2% and 83.4% respectively. The positive (PPV) and negative predictive values (NPV) were 47.1% and 97.9%. By excluding patients who had positive deletion of chromosome 9, the overall results of the screening test improved: sensitivity 84.6%; specificity 96.4%; PPV 75.9% and NPV 97.9%. Conclusions: UroVysion FISH has a high specificity of detecting urothelial cancer or dysplasia when deletion of chromosome 9 is excluded. Negative UroVysion FISH-tests may allow us to conserve health resources and minimize trauma by deferring cystoscopic or ureteroscopic examination.

• Childhood Kidney Diseases
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• v.16 no.2
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• pp.73-79
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• 2012

Purpose: The association of mitochondrial DNA (mtDNA) mutations, deletions and copy number with progressive changes in patients with some glomerular disease and end-stage renal disease have been reported. In this study, we performed mtDNA mutation analysis in children with IgA nephropathy to investigate its role in progressive clinical course. Methods: Seven children with IgA nephropathy were involved in this study. MtDNA isolated from platelet was amplified by PCR and sequenced entirely. Results: The mean age at renal biopsy was $11.5{\pm}2.2$ year and the mean age at latest evaluation was $17.9{\pm}3.2$ year. The mean follow-up period were $7.8{\pm}3.1$ years. Patients was divided into 2 groups according to the amount of proteinuria at presenting manifestation. Group 2 patients were nephrotic syndrome. Renal function reveals within normal range in all patients. In group 2 patients, the mean serum albumin level was significantly lower than those of group 1 ($3.7{\pm}0.6g/dL$ vs. $4.7{\pm}0.2g/dL$, P=0.0241) and the mean total cholesterol level was significantly higher than those of group 1 ($222.7{\pm}35.7mg/dL$ vs. $148.3{\pm}29.1mg/dL$, P=0.0283). In Group 2 patients, total amount of protein of 24 hour collected urine also significantly higher than those of group 1 ($1,466.0{\pm}742.5mg$ vs. $122.5{\pm}48.1mg$, P=0.0135). Pr/Cr ratio in random urine sample was also higher in group 2 than those of group 1 but the statistical significance was not noted ($1.8{\pm}1.6$ vs. $0.2{\pm}0.2$, P=0.0961). Deletion of mtDNA nt 8272-8281 were observed in two patients, one patient in each groups, respectively. This is noncoding lesion. No patients demonstrated the mtDNA mutations. Conclusions: We have identified a deletion of mtDNA nt 8272-8281 in two children with IgA nephropathy. Further studies are needed to clarify the role of mitochondrial function in the progressive change of IgA nephropathy.

• Journal of Microbiology and Biotechnology
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• v.23 no.10
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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.

• Korean Journal of Microbiology
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• v.28 no.1
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• pp.35-40
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• 1990

The restriction clevage map of multi-copy recombinant plasmid, pJY712(8.1kb), carrying the thiostrepton resistance gene(tsr) was determined. pJY712 had a broad host range in Streptomyces and contained single BglII site for cloning purpose. The plasmid showed the phenomenon of lethal zygosis ($Ltz^{+}$). Transformation frequency of pJY712 was $5.0\times 10^{4}$ transformants per ug plasmid DNA (TFU) in S. lividans. Plasmid pJY713 was constructed by inserting the tyrosinase gene(mel) into the BclI site of pJY712. Recombinant plasmid pJY714 carrying the mel gene was constructed by in vitro deletion of a segment (1.9kb BglII-BclI fragment) from pJY713.