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Hye Sook Han,Jieun Yun,Sang-Bae Han,Hong Jun Kim,Se-il Go,Won Sup Lee,Woo Kyun Bae,Sang-Hee Cho,Eun-Kee Song,Ok-Jun Lee,양예원,Yaewon Yang,Jihyun Kwon,Hee Bok Chae,한혜숙,김희경,이기형 대한위암학회 2019 Journal of gastric cancer Vol.19 No.3
Purpose: Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremelypoor prognosis. Malignant ascites samples are the most appropriate biological material touse to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomalMicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites(LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated theirrole as diagnostic biomarkers for GC-ascites. Materials and Methods: Total RNA was extracted from exosomes isolated from 165 ascitessamples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen theexpression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitativereverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were performed tovalidate the expression levels of selected exosomal miRNAs in the training (n=70) andvalidation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels weredetermined in ascites samples. Results: The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantlydownregulated in the GC-ascites samples compared to the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve[AUC]=0.798 and 0.846 for the training and validation cohorts, respectively). The diagnosticperformance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5pand CEA (AUC=0.981 and 0.946 for the training and validation cohorts, respectively). Conclusions: We identified exosomal miRNAs capable of distinguishing between non-malignant and GC-ascites, showing that the combined use of miR-181b-5p and CEA couldimprove diagnosis.
Hye Won Chae,Haehum Jung,Eun Jung Kim,Hyun Joo Shim,Joong In Lim,Hye Young Ji,Hye Suk Lee 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.9
(S)-2-ethoxy-3-(4-{3-methyl-5-[4-(3-methyl-isoxazol-5-yl)-phenyl]thiophen-2-ylmethoxy}-phenyl)-propionic acid (PAM-1616) is a novel peroxisome proliferators-activated receptor γ (PPARγ) partial agonist with excellent antihyperglycemic activity. It is a promising new drug candidate for the treatment of type-2 diabetes with reduced possibility of edema in vitro/in vivo. In order to evaluate the pharmacokinetics of PAM-1616, a reliable, selective and sensitive highperformance liquid chromatography/electrospray ionization tandem mass spectrometry was developed for the quantification of PAM-1616 in rat plasma. The analytes were extracted from rat plasma with ethyl acetate, separated on an Atlantis dC18 column with a mobile phase of 75% acetonitrile in 10 mM ammonium formate (pH 4.5), and detected by tandem mass spectrometry in the selective reaction monitoring mode. The calibration curve was linear (r2 = 0.999) over the concentration range of 0.05-20.0 μg/mL and the lower limit of quantification was 0.05 μg/mL. The coefficient of variation and relative error at four QC levels were 1.8% to 14.3% and −10.0% to 6.5%, respectively. The present method was successfully applied to the pharmacokinetic study of PAM-1616 after intravenous administration of PAM-1616 potassium at a dose of 1 mg/kg in rats.
Effect of Ion-Pair Formation with Bile Salts on the In Vitro Cellular Transport of Berberine
Chae, Hye-Won,Kim, In-Wha,Jin, Hyo-Eon,Kim, Dae-Duk,Chung, Suk-Jae,Shim, Chang-Koo 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.1
The objective of this study was to examine the effect of ion-pair complexation with endogenous bile salts on the transport of a quarternary ammonium organic cationic (OC) drug, berberine, across the Caco-2 and LLC-PK1 cell monolayers. The basolateral-to-apical (BL-AP) transport of berberine in Caco-2 cells was temperature dependent and 10-fold higher than that of the apical-to-basolateral (AP-BL) transport. Similar results were observed for the transport of berberine across the LLC-PK1 cells. Moreover, the BL-AP transport in the Caco-2 cells was significantly reduced by the cis-presence of P-glycoprotein (P-gp) inhibitors such as cyclosporine A, verapamil, and digoxin. These results suggest that an efflux transporter, probably P-gp, is involved in the Caco-2 cell transport. The $K_m$ and $V_{max}$ values for the carrier-mediated transport were estimated to be 83.4 mM and 7640 pmole/h/$cm^2$, respectively. The apparent partition coefficient (APC) of berberine between n-octanol and a phosphate buffer (pH 7.4) was increased by the presence of an organic anion (OA), taurodeoxycholate (TDC, a bile salt), suggesting the formation of a lipophilic ion-pair complex between an OC (berberine) and an OA (TDC). Despite the ion-pair complexation, however, the BL-AP transport of berberine across the Caco-2 and LLC-PK1 cells was not altered by the cis-presence of bile salts or the rat bile juice. This is consistent with the reportedly unaltered secretory transport of a quarternary ammonium compound, tributylmethylammonium (TBuMA), across the Caco-2 cell monolayers in the cis-presence of bile salts or the rat bile juice, but not with our previous report in which the secretory transport of TBuMA across the LLC-PK1 cell was increased in the cis-presence of TDC. Therefore, the effect of ion-pair formation with the bile components or bile salts on the secretory transport of OCs appears to depend on the molecular properties of OCs (e.g., molecular weight, lipophilicity and affinity to relevant transporters) and the characteristics of cell strains (e.g., expression and contribution of responsible transporters to the transport).
Effect of Ion-Pair Formation with Bile Salts on the In Vitro Cellular Transport of Berberine
Hye-Won Chae,김인화,진효언,김대덕,정석재,심창구 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.1
The objective of this study was to examine the effect of ion-pair complexation with endogenous bile salts on the transport of a quarternary ammonium organic cationic (OC) drug, berberine, across the Caco-2 and LLC-PK1 cell monolayers. The basolateral-to-apical (BL-AP) transport of berberine in Caco-2 cells was temperature dependent and 10-fold higher than that of the apical-to-basolateral (AP-BL) transport. Similar results were observed for the transport of berberine across the LLC-PK1 cells. Moreover, the BL-AP transport in the Caco-2 cells was significantly reduced by the cis-presence of P-glycoprotein (P-gp) inhibitors such as cyclosporine A, verapamil, and digoxin. These results suggest that an efflux transporter, probably P-gp, is involved in the Caco-2 cell transport. The Km and Vmax values for the carrier-mediated transport were estimated to be 83.4 mM and 7640 pmole/h/cm2, respectively. The apparent partition coefficient (APC) of berberine between n-octanol and a phosphate buffer (pH 7.4) was increased by the presence of an organic anion (OA), taurodeoxycholate (TDC, a bile salt), suggesting the formation of a lipophilic ion-pair complex between an OC (berberine) and an OA (TDC). Despite the ion-pair complexation, however, the BL-AP transport of berberine across the Caco-2 and LLC-PK1 cells was not altered by the cis-presence of bile salts or the rat bile juice. This is consistent with the reportedly unaltered secretory transport of a quarternary ammonium compound, tributylmethylammonium (TBuMA), across the Caco-2 cell monolayers in the cis-presence of bile salts or the rat bile juice, but not with our previous report in which the secretory transport of TBuMA across the LLC-PK1 cell was increased in the cis-presence of TDC. Therefore, the effect of ion-pair formation with the bile components or bile salts on the secretory transport of OCs appears to depend on the molecular properties of OCs (e.g., molecular weight, lipophilicity and affinity to relevant transporters) and the characteristics of cell strains (e.g., expression and contribution of responsible transporters to the transport).
Intrapartum predictive factors for failure of vaginal delivery in nulliparous women
( Hye Jung Cho ),( Hyun Soo Park ),( Chae Hyeong Lee ),( Sang Ho Yoon ),( Ju-won Roh ),( Hayan Kwon ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-
Objective: This study was to identify intrapartum potential predictive factors for failure of vaginal delivery in nulliparous women undergoing a trial of labor. Methods: Retrospective study of singleton pregnancy in nulliparous women between 36 and 42 0/7 weeks conducted from 2007 through 2017. A failure of vaginal delivery was defined as a delivery that was initially attempted a vaginal delivery but was converted to emergency cesarean section. Pregnancies which need to cesarean section including preeclampsia, chronic hypertension, placenta previa, or cesarean section due to fetal anomalies or intrauterine growth restriction (IUGR) were excluded. Odds ratios (OR) and confidence intervals (CI) for emergency cesarean section were calculated with multivariable logistic regression to assess the risk for failure of vaginal delivery. Results: 2240 trials of vaginal delivery were performed in nulliparous women of which 457 (20.4%) failed. Among these women, 457 cases who underwent emergency cesarean section were compared to the data of 952 women who underwent a successful vaginal delivery. Predictors for failure of vaginal delivery were related with maternal pre-pregnant body mass index (OR 1.02), maternal height (OR 0.94 per cm), initial cervical effacement (OR 0.98), initial cervical dilatation (OR 0.73), premature rupture of membrane (OR 0.54), station of descent of the fetal head (OR 0.61 per station more descended), estimated fetal weight 3500g as compared to <3500g (OR 2.4). Maternal age, gestational age, induction and use of epidural anesthesia were not useful for predicting failed vaginal delivery. Conclusion: Failed vaginal delivery can be predicted using intrapartum characteristics. Premature rupture of membrane and estimated fetal weight is significantly related with emergency cesarean section. During labor, accurate measurement of fetal weight and amniotomy are helpful to progress successful labor.
Won, Hye Sung,Maeng, Lee So,Chae, Hiun Suk,Kim, Hyung Keun,Cho, Young Suk,Kang, Jin-Hyoung,Jang, Hong Seok,Ryu, Mi-Ryeong The Korean Society of Gastroenterology; the Korean 2012 Gut and Liver Vol.6 No.2
<P><B>Background/Aims</B></P><P>The purpose of this study was to investigate the malignant potential of aberrant crypt foci (ACF) by measuring the multiplicity of crypts and lectin expression in the early and late stages of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis.</P><P><B>Methods</B></P><P>Six-week-old Wistar rats were injected subcutaneously with DMH for 27 weeks. We classified ACF according to the number of crypts per ACF as a few crypts (≤3 crypts, FC ACF) or numerous crypts (≥4 crypts, NC ACF). Immunohistochemistry was used to evaluate lectin expression.</P><P><B>Results</B></P><P>In the early stage, FC ACF (590/1,902, 31.0%) occurred more frequently than NC ACF (35/449, 7.8%); whereas in the late stage, NC ACF (176/449, 39.2%) occurred more frequently than FC ACF (324/1,902, 17.0%). The number of ACF peaked at 15 to 20 weeks. The ratio of NC/FC ACF increased gradually during carcinogenesis. The expression of both UEA1 and PNA was higher in NC ACF than FC ACF. Lectin expression increased in the late stage compared with the early stage.</P><P><B>Conclusions</B></P><P>The expression of lectin was higher in NC ACF and ACF in the late stage. Therefore, ACF with higher multiplicities in the late stage may have more malignant potential in DMH-induced colon carcinogenesis.</P>