• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.368-379
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• 2022

Hyaluronic acid (HA), a ligand of CD44, accumulates in some types of tumors and is responsible for tumor progression. The nuclear factor erythroid 2-like 2 (NRF2) regulates cytoprotective genes and drug transporters, which promotes therapy resistance in tumors. Previously, we showed that high levels of CD44 are associated with NRF2 activation in cancer stem like-cells. Herein, we demonstrate that HA production was increased in doxorubicin-resistant breast cancer MCF7 cells (MCF7-DR) via the upregulation of HA synthase-2 (HAS2). HA incubation increased NRF2, aldo-keto reductase 1C1 (AKR1C1), and multidrug resistance gene 1 (MDR1) levels. Silencing of HAS2 or CD44 suppressed NRF2 signaling in MCF7-DR, which was accompanied by increased doxorubicin sensitivity. The treatment with a HAS2 inhibitor, 4-methylumbelliferone (4-MU), decreased NRF2, AKR1C1, and MDR1 levels in MCF7-DR. Subsequently, 4-MU treatment inhibited sphere formation and doxorubicin resistance in MCF7-DR. The Cancer Genome Atlas (TCGA) data analysis across 32 types of tumors indicates the amplification of HAS2 gene is a common genetic alteration and is negatively correlated with the overall survival rate. In addition, high HAS2 mRNA levels are associated with increased NRF2 signaling and poor clinical outcome in breast cancer patients. Collectively, these indicate that HAS2 elevation contributes to chemoresistance and sphere formation capacity of drug-resistant MCF7 cells by activating CD44/NRF2 signaling, suggesting a potential benefit of HAS2 inhibition.

• Korean Journal of Clinical Pharmacy
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• v.33 no.1
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• pp.1-7
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• 2023

Background: Along with the increase in the elderly population, concerns about polypharmacy, which can cause medication-related problems, are increasing. This study aimed to find out the association between drug-related factors and readmission in elderly patients within 30 days after discharge. Methods: Data of patients aged ≥65 years who were discharged from the respiratory medicine ward of a tertiary hospital between January and March 2016 were retrospectively obtained. The medication regimen complexity at discharge was calculated using the medication regimen complexity index (MRCI) score, comorbidity status was assessed using the Charlson comorbidity index (CCI), potentially inappropriate medications (PIMs) were evaluated based on the Beer 2019 criteria, and adverse drug events (ADEs) were examined using the ADE reporting system. Multivariable logistic regression analysis was used to evaluate the effect of medication-related problems on hospital readmission after controlling for other variables. Results: Of the 206 patients included, 84 (40.8%) used PIMs, 31 (15%) had ADEs, and 32 (15.5%) were readmitted. The mean age, total medications, MRCI, CCI, and PIMs in the readmission group were significantly higher than those in the non-readmission group. Age significantly decreased the risk of readmission (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.84-0.96) after adjusting for sex, length of hospital stay, and ADEs. The use of PIMs (OR, 2.38; 95% CI, 1.10-5.16) and increased CCI (OR, 1.50; 95% CI, 1.16-1.93) and MRCI (OR, 1.04; 95% CI, 1.01-1.07) were associated with an increased occurrence of readmission. Conclusion: PIMs were associated with a significantly greater risk for readmission than MRCI.

• Genomics & Informatics
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• v.21 no.2
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• pp.20.1-20.10
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• 2023

Aromatase inhibitors (AI) are drugs that are widely used in treating estrogen receptor (ER)-positive breast cancer patients. Drug resistance is a major obstacle to aromatase inhibition therapy. There are diverse reasons behind acquired AI resistance. This study aims at identifying the plausible cause of acquired AI resistance in patients administered with non-steroidal AIs (anastrozole and letrozole). We used genomic, transcriptomic, epigenetic, and mutation data of breast invasive carcinoma from The Cancer Genomic Atlas database. The data was then separated into sensitive and resistant sets based on patients' responsiveness to the non-steroidal AIs. A sensitive set of 150 patients and a resistant set of 172 patients were included for the study. These data were collectively analyzed to probe into the factors that might be responsible for AI resistance. We identified 17 differentially regulated genes (DEGs) among the two groups. Then, methylation, mutation, miRNA, copy number variation, and pathway analyses were performed for these DEGs. The top mutated genes (FGFR3, CDKN2A, RNF208, MAPK4, MAPK15, HSD3B1, CRYBB2, CDC20B, TP53TG5, and MAPK8IP3) were predicted. We also identified a key miRNA - hsa-mir-1264 regulating the expression of CDC20B. Pathway analysis revealed HSD3B1 to be involved in estrogen biosynthesis. This study reveals the involvement of key genes that might be associated with the development of AI resistance in ER-positive breast cancers and hence may act as a potential prognostic and diagnostic biomarker for these patients.

• Journal of Microbiology and Biotechnology
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• v.34 no.5
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• pp.1164-1177
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• 2024

Esophageal squamous cell carcinoma (ESCC) is among the most common malignant tumors of the digestive tract, with the sixth highest fatality rate worldwide. The ESCC-related dataset, GSE20347, was downloaded from the Gene Expression Omnibus (GEO) database, and weighted gene co-expression network analysis was performed to identify genes that are highly correlated with ESCC. A total of 91 transcriptome expression profiles and their corresponding clinical information were obtained from The Cancer Genome Atlas database. A mitochondria-associated risk (MAR) model was constructed using the least absolute shrinkage and selection operator Cox regression analysis and validated using GSE161533. The tumor microenvironment and drug sensitivity were explored using the MAR model. Finally, in vitro experiments were performed to analyze the effects of hub genes on the proliferation and invasion abilities of ESCC cells. To confirm the predictive ability of the MAR model, we constructed a prognostic model and assessed its predictive accuracy. The MAR model revealed substantial differences in immune infiltration and tumor microenvironment characteristics between high- and low-risk populations and a substantial correlation between the risk scores and some common immunological checkpoints. AZD1332 and AZD7762 were more effective for patients in the low-risk group, whereas Entinostat, Nilotinib, Ruxolutinib, and Wnt.c59 were more effective for patients in the high-risk group. Knockdown of TYMS significantly inhibited the proliferation and invasive ability of ESCC cells in vitro. Overall, our MAR model provides stable and reliable results and may be used as a prognostic biomarker for personalized treatment of patients with ESCC.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.233-239
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• 2024

N6-methyladenosine (m6A) RNA methylation has recently emerged as a significant co-transcriptional modification involved in regulating various RNA functions. It plays a vital function in numerous biological processes. Enzymes referred to as m6A methyltransferases, such as the methyltransferase-like (METTL) 3-METTL14-Wilms tumor 1 (WT1)-associated protein (WTAP) complex, are responsible for adding m6A modifications, while m6A demethylases, including fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), can remove m6A methylation. The functions of m6A-methylated RNA are regulated through the recognition and interaction of m6A reader proteins. Recent research has shown that m6A methylation takes place at multiple sites within hepatitis B virus (HBV) RNAs, and the location of these modifications can differentially impact the HBV infection. The addition of m6A modifications to HBV RNA can influence its stability and translation, thereby affecting viral replication and pathogenesis. Furthermore, HBV infection can also alter the m6A modification pattern of host RNA, indicating the virus's ability to manipulate host cellular processes, including m6A modification. This manipulation aids in establishing chronic infection, promoting liver disease, and contributing to pathogenesis. A comprehensive understanding of the functional roles of m6A modification during HBV infection is crucial for developing innovative approaches to combat HBV-mediated liver disease. In this review, we explore the functions of m6A modification in HBV replication and its impact on the development of liver disease.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2004.11a
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• pp.153-156
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• 2004

Korea Food and Drug Administration(KFDA) has peformed the calibration of therapy level dosimeters for Co-60 radiation since 1979. The reference standard ionization chamber has been calibrated at BIPM in France. The uncertainty on the KFDA calibration coefficients is 0.9 %(k=2) for air kerma and absorbed dose to water. Since 1999 a national quality audit program for ensuring dosimetry accuracy in Korea radiotherapy centers has been performed by the KFDA. The uncertainty associated with the determination of the absorbed dose to water from the TLD readings for high energy x-ray is 1.6 %(k=1). The correction factors for energy, non-linearity dose response, and TLD holder are used in the dose determination. Agreement between the user stated dose and KFDA measured dose within ${\pm}$ 5 % is considered acceptable. KFDA TLD postal dose quality audit program was peformed for 71 beam qualities of 53 domestic radiotherapy centers in 2003. The results for quality assurance showed that 63 out of 71 beam qualifies (89 %) satisfied the acceptance limit. The second audit was carried out for the centers outside the limit and ail of them have been corrected.

• Quality Improvement in Health Care
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• v.8 no.1
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• pp.22-42
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• 2001

Background : A study comparing unit dose drug distribution system(UDS) versus traditional drug distribution system(TDS) was conducted in Seoul National University Hospital. The objectives of this study were to identify safer drug distribution system and to measure the efficiency of both systems in utilizing nursing and pharmacist's time. Methods : The study was designed to compare the data on medication errors, nursing time and pharmacists' time before and after implementation of the UDS in the internal medicine and otorhinolaryngology care units. The data on actual medications administered to patients were obtained by a disguised observer during the study period. The data collected were then compared with the physicians' orders to determine the rate of medication errors. In addition, using ten-minute interval work-sampling method nursing and pharmacists' time were measured. Results : About 6% of medications were administered incorrectly in the TDS, in comparison to 1.6% in the UDS. The rate of medication error decreased significantly in the UDS compared with the TDS. Mean times spent on medication-related activities by nurses were 34.1% in the TDS and 28.5% in the UDS. In the internal medicine care unit, nursing time associated with medications decreased significantly after the implementation of the UDS, but the reduction in medication-related nursing time in the otorhinolaryngology care unit was not significant. Pharmacist's medication-related work activities, increased from 2% in the TDS to 20% in the UDS. Pharmacist's time spent on therapy-related activities increased significantly. Conclusion : The rate of medication errors in the UDS decreased significantly compared with the TDS. Time spent on medication-related activities decreased for nurses while it increased for pharmacists. In summary, the UDS was estimated to be safer and to utilize of pharmacists' and nursing time more efficiently than the TDS.

• Polymer(Korea)
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• v.38 no.3
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• pp.333-337
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• 2014

PVC (polyvinyl chloride) intravenous fluid bags and tubes that contain DEHP (diethylhexyl phthalate) as a plasticizer have several associated disadvantages for intravenous injections. We investigated the drug absorption behaviors on the inner surface of an infusion tube that consisted of commercialized PVC/PU (polyurethane). We developed a non-PVC (polyolefin) tube in order to improve the efficacy of this drug administration method. We prepared four types of non-PVC (polyolefin) infusion tubes using a polyethylene (PE), polypropylene (PP), syndiotactic 1,2-polybutadiene (PB), and styrene-ethylene (SE) copolymer elastomers were prepared using a single screw extruder. The four types of manufactured non-PVC (polyolefin) infusion tubes had good mechanical properties that were equivalent to PVC tube properties. The four types of prepared non-PVC (polyolefin) infusion tubes also prohibited drug absorption when compared to the commercialized PVC and PU tubes. Therefore, based on the results of this study, prepared non-PVC (polyolefin) tubes are good candidates for infusion because they prevent drug absorption and the release of DEHP.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.642-653
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• 2021

Background: Effective strategies are dramatically needed to prevent and improve the recovery from myocardial ischemia and reperfusion (I/R) injury. Direct interactions between the mitochondria and endoplasmic reticulum (ER) during heart diseases have been recently investigated. This study was designed to explore the cardioprotective effects of gypenoside XVII (GP-17) against I/R injury. The roles of ER stress, mitochondrial injury, and their crosstalk within I/R injury and in GP-17einduced cardioprotection are also explored. Methods: Cardiac contractility function was recorded in Langendorff-perfused rat hearts. The effects of GP-17 on mitochondrial function including mitochondrial permeability transition pore opening, reactive oxygen species production, and respiratory function were determined using fluorescence detection kits on mitochondria isolated from the rat hearts. H9c2 cardiomyocytes were used to explore the effects of GP-17 on hypoxia/reoxygenation. Results: We found that GP-17 inhibits myocardial apoptosis, reduces cardiac dysfunction, and improves contractile recovery in rat hearts. Our results also demonstrate that apoptosis induced by I/R is predominantly mediated by ER stress and associated with mitochondrial injury. Moreover, the cardioprotective effects of GP-17 are controlled by the PI3K/AKT and P38 signaling pathways. Conclusion: GP-17 inhibits I/R-induced mitochondrial injury by delaying the onset of ER stress through the PI3K/AKT and P38 signaling pathways.

• BMB Reports
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• v.55 no.11
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• pp.565-570
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• 2022

Pulmonary arterial hypertension (PAH) is a progressive and devastating disease whose pathogenesis is associated with a phenotypic switch of pulmonary arterial vascular smooth muscle cells (PASMCs). Bone morphogenetic protein (BMP) signaling and potassium two pore domain channel subfamily K member 3 (KCNK3) play crucial roles in PAH pathogenesis. However, the relationship between BMP signaling and KCNK3 expression in the PASMC phenotypic switching process has not been studied. In this study, we explored the effect of BMPs on KCNK3 expression and the role of KCNK3 in the BMP-mediated PASMC phenotypic switch. Expression levels of BMP receptor 2 (BMPR2) and KCNK3 were downregulated in PASMCs of rats with PAH compared to those in normal controls, implying a possible association between BMP/BMPR2 signaling and KCNK3 expression in the pulmonary vasculature. Treatment with BMP2, BMP4, and BMP7 significantly increased KCNK3 expression in primary human PASMCs (HPASMCs). BMPR2 knockdown and treatment with Smad1/5 signaling inhibitor substantially abrogated the BMP-induced increase in KCNK3 expression, suggesting that KCNK3 expression in HPASMCs is regulated by the canonical BMP-BMPR2-Smad1/5 signaling pathway. Furthermore, KCNK3 knockdown and treatment with a KCNK3 channel blocker completely blocked BMP-mediated anti-proliferation and expression of contractile marker genes in HPAMSCs, suggesting that the expression and functional activity of KCNK3 are required for BMP-mediated acquisition of the quiescent PASMC phenotype. Overall, our findings show a crosstalk between BMP signaling and KCNK3 in regulating the PASMC phenotype, wherein BMPs upregulate KCNK3 expression and KCNK3 then mediates BMP-induced phenotypic switching of PASMCs. Our results indicate that the dysfunction and/or downregulation of BMPR2 and KCNK3 observed in PAH work together to induce aberrant changes in the PASMC phenotype, providing insights into the complex molecular pathogenesis of PAH.