• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10847-10853
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• 2015

Background: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positive breast cancer. However, acquired drug resistance has become a very serious clinical problem that hampers the use of this agent. In this study, we aimed to screen small molecule drugs that might reverse lapatinib-resistance of breast cancer by exploring differentially expressed genes (DEGs) via a bioinformatics method. Materials and Methods: We downloaded the gene expression profile of BT474-J4 (acquired lapatinib-resistant) and BT474 (lapatinib-sensitive) cell lines from the Gene Expression Omnibus (GEO) database and selected differentially expressed genes (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses were performed with the DAVID database. Finally, a connectivity map was utilized for predicting potential chemicals that reverse lapatinib-resistance. Results: A total of 1, 657 DEGs were obtained. These DEGs were enriched in 10 pathways, including cell cycling, regulation of actin cytoskeleton and focal adhesion associate examples. In addition, several small molecules were screened as the potential therapeutic agents capable of overcoming lapatinib-resistance. Conclusions: The results of our analysis provided a novel strategy for investigating the mechanism of lapatinib-resistance and identifying potential small molecule drugs for breast cancer treatment.

• Korean Chemical Engineering Research
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• v.44 no.1
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• pp.1-9
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• 2006

Biodevices composed of biomolecular layer by mimicking the natural functions of cells and the interaction mechanisms of the constituted biomolecules have been developed in various industrial fields such as medical diagnosis, drug screening, electronic device, bioprocess, and environmental pollution detection. To construct biodevices such as bioelectronic devices (biomolecular diode, bio-information storage device and bioelectroluminescence device), protein chip, DNA chip, and cell chip, biomolecules including DNA, protein, and cells have been used. Fusion technology consisting of immobilization technology of biomolecules, micro/nano-scale patterning, detection technology, and MEMs technology has been used to construct the biodevices. Recently, nanotechnology has been applied to construct nano-biodevices. In this paper, the current technology status of biodevice including its fabrication technology and applications is described and the future development direction is proposed.

• Clinical and Experimental Pediatrics
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• v.45 no.12
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• pp.1546-1550
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• 2002

Purpose : The authors carried out this study to determine the relationship between vigabatrin (VGB) and visual field defect.. Methods : Seventy eight patients older than 8 years who had epilepsy which had developed and been diagnosed, and were receiving add-on therapy, were the subjects of this study. If suspicious results were obtained from the initial test with the Humphrey automatic perimeter, the patient was tested again with the Goldman perimeter. Follow-up examinations were performed on these patients after 6 months. Results : In this study, five of the 78 patients had suspicious primary test results, but upon the second examination they were all found to be normal. Thus there were no patients with visual field defects. Conclusion : VGB is a drug which may cause visual field defects, but in this study no patients presented with this symptom. Instead of limiting the use of VGB due to the adverse effect of visual field defect in the initial treatment of partial seizure and infantile spasm untreatable with other medication, if used with care it may not cause serious problems. Screening for visual defect is recommended, and in patients taking VGB regular examination is necessary.

• Journal of Microbiology and Biotechnology
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• v.14 no.1
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• pp.97-104
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• 2004

Water-sludge bacteria were screened to find a lipase enantioselectively hydrolyzing itraconazole precursor, which is well known as the starting material of antifungal drug agents. A bacterial strain was isolated and identified as Acinetobacter junii SY-01. After the strain was cultivated, the enzyme was purified 39.4-fold using ultrafiltration and gel filtration through a Sephadex G-100 chromatographic column and the activity yield was 34.9%. The molecular weight of the enzyme was about 40 kDa, as measured by SDS-PAGE, and the optimum pH was 7.0- 9.0 and stable at pH 6.0- 9.0. The optimum temperature was 45- $5^{\circ}C$, and 73% of the enzymes activity remained after incubation at 70% for 1 h. Enzyme activity was enhanced by gall powder, sodium deoxycholate, a cationic detergent Tween 80, and a non-ionic detergent Triton X-100, but was markedly inhibited by metal ions such as $Hg^{2＋},Cu^{2＋},Ni^{2＋}/,Ca^{2＋}$, and an anionic-surfactant sodium dodecylsulfate. The $K_{m}$ values for (R)- and (S)-enantiomers of the itraconazole precursor were 0.385 and 21.83 mM, respectively, and the $V_{max} values ($\mu$Mㆍmin^{-1}.)$ were 6.73 and 6.49, respectively. The acetyl group among the different acyl moieties of itraconazole precursor showed the highest enantioselectivity for the hydrolysis by the Acinetobacter junii SY-01 lipase, and the lipase from Acinetobacter junii SY-01 displayed better enantioselectivity than that of commercially available lipases and esterases.

• Journal of Microbiology and Biotechnology
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• v.30 no.5
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• pp.662-667
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• 2020

Epidermal growth factor receptor (EGFR) mutations are not only genetic markers for diagnosis but also biomarkers of clinical-response against tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). Among the EGFR mutations, the in-frame deletion mutation in EGFR exon 19 kinase domain (EGFR exon 19-del) is the most frequent mutation, accounting for about 45% of EGFR mutations in NSCLCs. Development of sensitive method for detecting the EGFR mutation is highly required to make a better screening for drug-response in the treatment of NSCLC patients. Here, we developed a fluorometric tandem gene amplification assay for sensitive detection of low-abundance EGFR exon 19-del mutant genomic DNA. The method consists of pre-amplification with PCR, thermal cycling of ligation by Taq ligase, and subsequent rolling circle amplification (RCA). PCR-amplified DNA from genomic DNA samples was used as splint DNA to conjugate both ends of linear padlock DNA, generating circular padlock DNA template for RCA. Long stretches of ssDNA harboring multiple copies of G-quadruplex structure was generated in RCA and detected by thioflavin T (ThT) fluorescence, which is specifically intercalated into the G-quadruplex, emitting strong fluorescence. Sensitivity of tandem gene amplification assay for detection of the EGFR exon 19-del from gDNA was as low as 3.6 pg, and mutant gDNA present in the pooled normal plasma was readily detected as low as 1% fraction. Hence, fluorometric detection of low-abundance EGFR exon 19 deletion mutation using tandem gene amplification may be applicable to clinical diagnosis of NSCLC patients with appropriate TKI treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.671-676
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• 2005

In this study, we investigated the antioxidant effect of extract from Monascus pillosus, on the human wild-type p53 and p21 expressing A549 lung epithelial cell line and MCF-7 mammary adenocarcinoma cell line stimulated by NO. $P21^{waf/cip1}$ was identified as a gene induced in senescent cells. It is a cyclin-dependent kinase inhibitor and has been shown to cause cell cycle arrest and apoptosis. While p53-regulated stimulation of p21 appears to be central for the permanent growth-arrest, the role of p21 in p53-triggered cell death is unclear. Low dose of sodium nitroprusside (SNP) induced the development of senescence associated with increased expression of p53 and p21 in A549 cells. Inhibition of p21 transactivating activity requires high level correlates with the amount of p53 necessary to cause cell death. Association of p21 and p53 results in inhibition of p21-stimulated transcription. This requires a higher p53 level than is necessary for transcriptional activation of endogenous p53-responsive gene but correlates well with the level of p53 necessary to cause cell death. Exposure to W-1 inhibited oxidative stresses-induced senescence-like arrest, resulting in a significant reduction in p53 and p21 steady state levels. These results suggest that p53 and p21 play a central role in the onset of senescence. Thus, it is important to emphasize control of oxidative balance in tumor prevention and aging.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.6
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• pp.657-661
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• 2014

Gilbert's syndrome is one that shows a benign course with intermittent unconjugate hyperbilirubinemia without any evidence of hepatobiliary tract disease or hemolysis. It is often found in a health examination or blood laboratory test by chance. In particular, patients who are taking drugs, including herbal medicine should be careful for their medication due to the possibility of associations with changes in liver function because of drug metabolism, sometimes they have to quit the use of the medication for a certain period and often they should get an additional test. Two male patients increased serum total bilirubin level without other systemic symptoms in screening test for clinical herb medicine pharmacokinetics study. Therefor they was diagnosed with suspected Gilbert's syndrome. They had been calory deprivation test with 24 hours fasting state. They also performed liver function test and ultrasonogram for evaluation of hepatobiliary tract disease. Total serum bilirubin was markedly increased, especially unconjugate bilirubin level higher over the two times than base line after they had been calory deprivation for 24 hours, They was not found another abnormality all laboratory results and physical examination. This study is a report on two cases of hyperbilirubinemia, diagnosed as Gilbert's syndrome, which were found in the process of a clinical pharmacokinetic study of a decoction of medicinal herbs.

• Journal of Food Hygiene and Safety
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• v.27 no.1
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• pp.1-17
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• 2012

T-2 toxin and HT-2 toxin, belong to type A trichothecences, are the most toxic mycotoxins among the trichothecene family. These mycotoxins are commonly found in cereals such as maize, wheat, barley, oats and rice, and their occurrence in food can be of concern. This review investigated the current trends of patents and researches on T-2 toxin and HT-2 toxin pertaining to natural occurrence, toxicity, metabolism, risk assessment, analytical and screening methods, and reduction/detoxification techniques. As compared with other $Fusarium$ mycotoxins, there are limited data for natural occurrence and risk assessment, and regulatory limit and official analytical methods on T-2 toxin and HT-2 toxin in domestic and foreign countries. In particular, selective deacetylation at the C3 and/or C4 positions of T-2 toxin by carboxyesterase present in foods was reported to cause the disappearance of T-2 and the extremely high HT-2 recoveries. Currently, regulatory limits for T-2 and HT-2 are under discussion in EU. For enforcement purposes it is essential to have available precise and reliable analytical methods applicable at the regulatory levels for the T-2 toxin and HT-2 toxin and relevant commodities. In addition, a further study on natural occurrence, risk assessment and reduction/detoxification techniques will be recommended.

• Journal of the Korea Safety Management & Science
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• v.15 no.1
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• pp.293-301
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• 2013

The purpose of this study is to introduce the limit of previously used six sigma quality process evaluation metrics, $Z_{st}$ and $P_{pk}$, and a solution to overcome this drawback by using a metric based on performance evaluation of Z-factor quality innovation. Case analysis on projects from national six sigma contest from 2011 to 2012 is performed and literature review on new drug development HTS (High Throughput Screening) is used to propose innovative performance evaluation metrics. This research shows that experimental study on six sigma evaluation metric, $Z_{st}$ and $P_{pk}$, have no significance difference between industrial type (Manufacturing, Semi-Public Institute, Public Institute) and CTQ type (Product Technology Type CTQ, Process Technology Type CTQ). Following discovery characterize this quality improvement as fixed target type project. As newly developed moving target type of quality innovation performance metric Z-Factor is used for evaluating experimental study, hypothetical analysis suggests that $Z_{st}$ and $P_{pk}$ share different relationship or even show reciprocal relationship. Constraints of the study are relatively small sample size of only 37 projects from past 2 years and conflict on having interview and communication with six sigma quality practitioner for qualitative experimental study. Both moving target type six sigma innovation project and fixed target type improvement project or quality circle enables efficient ways for a better understanding and quality practitioner use by applying quality innovation performance metric. Downside of fixed target type quality performance evaluation metric, $Z_{st}$ and $P_{pk}$, is presented through experimental study. In contrast, advantage of this study is that high throughput requiring product technology, process technology and quantum leap typed innovation effect is evaluated based on precision and accuracy and Z-Factor that enables relative comparison between enterprises is proposed and implemented.

• YAKHAK HOEJI
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• v.49 no.3
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• pp.237-243
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• 2005

Present study was performed for the development of a new supplementary product with gastroprotective effect. The preliminary screening were conducted for the effects of HCl-ethanol-induced gastric lesions in rats. Samples were aloe gel, active hexose correlated compound (AHCC) mentioned that have GI protective property and pulmuone healthy aloe gel (PHAG) that mixture of natural products from Pulmuone company. Aloe gel significantly inhibited HCl-ethanol-induced gastric lesions at the oral dose of 5 ml/kg. AHCC showed the strongest effectiveness at the oral dose of 1,200 mg/kg. PHAG also showed the significant effects at the oral dose of 10, 20 g/kg. In pylorus ligated rats, the treatments of aloe gel, AHCC and PHAG showed decrease in the volume of gastric secretion and acid output. And aloe gel, AHCC and PHAG significantly suppressed the aspirin-induced ulcer and chronic ulcer in pylorus ligated rats. The treatments of aloe gel and PHAG significantly reduced acetic acid-induced ulcer at the oral dose of 5 ml/kg and 10 g/kg for 12 days. In this study; we have found that PHAG had significant improvement in acute gastritis and ulcer at the dose of 20 g/kg and in chronic gastritis and ulcer at the dose of 10 g/kg. Also we evaluated the anti-bacterial activity against H. pylori treated with aloe gel, AHCC and PHAG. PHAG had a equivalent anti bacterial activity with ampicillin against H. pylori at the dose of 1 g/kg.