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Pureum Kang,Chang-Keun Cho,Choon-Gon Jang,Seok-Yong Lee,Yun Jeong Lee,Chang-Ik Choi,Jung-Woo Bae 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.5
Gliclazide metabolism is mediated by genetically polymorphic CYP2C9 and CYP2C19 enzymes. We investigated the effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide. Twenty-seven Korean healthy volunteers were administered a single oral dose of gliclazide 80 mg. The plasma concentration of gliclazide was quantified for the pharmacokinetic analysis and plasma concentrations of glucose and insulin were measured as pharmacodynamic parameters. The pharmacokinetics of gliclazide showed a significant difference according to the number of defective alleles of combined CYP2C9 and CYP2C19. The two defective alleles group (group 3) and one defective allele group (group 2) showed 2.34- and 1.46-fold higher AUC0–∞ (P < 0.001), and 57.1 and 32.3% lower CL/F (P < 0.001), compared to those of the no defective allele group (group 1), respectively. The CYP2C9IM–CYP2C19IM group had AUC0–∞ increase of 1.49-fold (P < 0.05) and CL/F decrease by 29.9% (P < 0.01), compared with the CYP2C9 Normal Metabolizer (CYP2C9NM)–CYP2C19IM group. The CYP2C9NM–CYP2C19PM group and CYP2C9NM–CYP2C19IM group showed 2.41- and 1.51-fold higher AUC0–∞ (P < 0.001), and 59.6 and 35.4% lower CL/F (P < 0.001), compared to those of the CYP2C9NM–CYP2C19NM group, respectively. The results represented that CYP2C9 and CYP2C19 genetic polymorphisms significantly affected the pharmacokinetics of gliclazide. Although the genetic polymorphism of CYP2C19 had a greater effect on the pharmacokinetics of gliclazide, the genetic polymorphism of CYP2C9 also had a significant effect. On the other hand, plasma glucose and insulin responses to gliclazide were not significantly affected by the CYP2C9–CYP2C19 genotypes, requiring further well-controlled studies with long-term dosing of gliclazide in diabetic patients.
Divergence dating of the two wing morphs in Vollenhovia emeryi (Hymenoptera: Myrmicinae)
Pureum Noh,Jaeyeon Kang,Jae Chun Choe,Gilsang Jeong 한국응용곤충학회 2015 한국응용곤충학회 학술대회논문집 Vol.2015 No.04
Vollenhovia emeryi (Hymenoptera: Myrmicinae) is dimorphic in its wing morphology of alate females: the long-winged and the short-winged. In our previous study, we found that the long-winged is ancestral and the short-winged is derived. Intriguingly, the former is infected with the intracellular symbiotic Wolbachia bacterium and the derived is void of the bacterium indicating that the latter somehow evolved resistance to the bacterium. This may be one of few cases in which transition from susceptibility to the bacterium can be traceable via the divergence estimation. As a consequence, we inferred that the two morphs diverged approximately quarter million years ago; a remarkably recent event in evolutionary perspective. In this presentation, we will further discuss genetic orchestration in the host insect and future research directions.
Temporal changes of Korean cicada in relation to meteorological factors
Jaeyeon Kang,Heejo Lee,Youngdon Ju,Bosun Park,Noori Choi,Pureum Noh,Eunok lee,Gilsang Jeong 한국응용곤충학회 2016 한국응용곤충학회 학술대회논문집 Vol.2016 No.04
In every summer, cicadas emerge and become numerically and ecologically dominant in Korean penninsula. Especially, cicada emergence is affected by the environmental factors. In order to evaluate the effect of environmental factors in cicada species, we analyzed the temporal changes in cicada exuviae based on meteorological and non-meteorological factors such as artificial light intensity and habitat characters on urban park area surrounded by residential houses. Combined multivariate analyses with a cluster analysis and a principal component analysis (PCA) were conducted. Samples were classified into 3 different cluster based on differences of meteorological factors such as temperature and humidity. Moreover, Random Forest model (RF) showed a high predictability of daily mean temperature on species peak abundance. These results provide a strong evidence that meteorological factors have significant effects on cicada emergences. Regarding the non-meteorological factors, we found no relationship in cicada emergence.
GDF-15 Levels Predict Efficacy in Lung Cancer Patients Treated with PD-1/ PD-L1 Inhibitors
( Da Hyun Kang ),( Pureum Sun ),( Chaeuk Chung ),( Song-i Lee ),( Dongil Park ),( Jeong Suk Koh ),( Yoonjoo Kim ),( Jeong Eun Lee ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.0
Background Growth and differentiation factor 15 (GDF-15) is a divergent member of the TGF-β superfamily. In disease states, such as acute injury, inflammation, and cancer, GDF-15 expression is dramatically increased. In cancer patients, elevated GDF-15 levels correlate with poor prognosis. In this study, we investigated whether GDF-15 levels can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. Methods This study included patients who were diagnosed with NSCLC and treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital from March 2018 to May 2020. We evaluated plasma GDF-15 levels and correlated the findings with clinical outcomes. Results In our cohort of 89 NSCLC patients, the mean plasma GDF-15 levels were 2475.86 pg/mL (794.07-4901.25). The objective response rate (ORR) was significantly higher in those with low GDF-15 (<1520 pg/mL) than those with high GDF-15 (ORR 35.5% vs. 15.5%, p=0.032). In 47 patients with blood sample post 2 months after treatment, the ORR and disease control rate (DCR) were significantly higher in patients with decreased GDF-15 levels compared to those with increased follow up GDF-15 levels (ORR 26.7% vs. 5.9%, p=0.028; DCR 73.3% vs. 35.3%, p=0.011). Conclusion Plasma GDF-15 levels could be a potential biomarker for predicting the efficacy in NSCLC patients treated with PD-1/PD-L1 inhibitors.
Chang-Keun Cho,Pureum Kang,Choon-Gon Jang,Seok-Yong Lee,YunJeong Lee,Chang-Ik Choi 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.12
Irbesartan, a potent and selective angiotensin II type-1 (AT1) receptor blocker (ARB), is one of the representative medications for the treatment of hypertension. Cytochrome P450 (CYP) 2C9 is primarily involved in the oxidation of irbesartan. CYP2C9 is highly polymorphic, and genetic polymorphism of this enzyme is the leading cause of significant alterations in the pharmacokinetics of irbesartan. This study aimed to establish the physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics of irbesartan in different CYP2C9 genotypes. The irbesartan PBPK model was established using the PK-Sim® software. Our previously reported pharmacogenomic data for irbesartan was leveraged in the development of the PBPK model and collected clinical pharmacokinetic data for irbesartan was used for the validation of the model. Physicochemical and ADME properties of irbesartan were obtained from previously reported data, predicted by the modeling software, or optimized to fit the observed plasma concentration–time profiles. Model evaluation was performed by comparing the predicted plasma concentration–time profiles and pharmacokinetic parameters to the observed results. Predicted plasma concentration–time profiles were visually similar to observed profiles. Predicted AUCinf in CYP2C9*1/*3 and CYP2C9*1/*13 genotypes were increased by 1.54- and 1.62-fold compared to CYP2C9*1/*1 genotype, respectively. All fold error values for AUC and Cmax in non-genotyped and CYP2C9 genotyped models were within the two-fold error criterion. We properly established the PBPK model of irbesartan in different CYP2C9 genotypes. It can be used to predict the pharmacokinetics of irbesartan for personalized pharmacotherapy in individuals of various races, ages, and CYP2C9 genotypes.