• Bulletin of the Korean Chemical Society
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• v.30 no.2
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• pp.293-294
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• 2009

• Journal of Preventive Medicine and Public Health
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• v.31 no.1 s.60
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• pp.1-14
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• 1998

The genetically determined CYP2D6 activity as considered to be associated with cancer susceptibility with inter-individual variation. Genetic polymorphism of CYP2D6(B) and CYP2D6(T) was determined by the two polymerase chain reaction(PCR) and BstN1 and EcoN1 restriction fragment length polymorphisms(RFLP) for 67 lung cancer cases and 95 healthy volunteer controls. The cases were composed of 26 squamous cell carcinoma, 14 small cell carcinoma, 10 adenocarcinoma, 3 large cell undifferentiated carcinoma, and 14 not histologically diagnosed. The results were gained from the 142 subjects (57 cases and 85 controls) who observed successfully in two PCR and BstNl/EcoN1 RELP. Only one and no mutant allele of the CYP2D6(B) and CYP2D6(T) gene was detected, that is, the frequency of mutant allele was very low; 0.7%(1/142) and 0%(0/142), respectively. Detected mutant allele of the CYP2D6(B) was beterozygous type(WM). The odds ratios for lung cancer susceptibility with CYP2D6(B) and CYP2D6(T) genotype were not calculated. These results are similar to the previous understanding that the mutant allele is very rare in Orientals compared to Caucasians, therefore, it considered that CYP2D6(B) and CYP2D6(T) genotypes have maybe no association with lung cancer susceptibility in Koreans. This is the basic data of CYP2D6(B) and CYP2D6(T) genotypes for Koreans. It would be hepful for further study to determine lung cancer susceptibility of Koreans with the data about CYP1A1, CYP2E1, GSTM1 from future study.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.510-519
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• 2022

Tofacitinib, a Janus kinase 1 and 3 inhibitor, is mainly metabolized by CYP3A1/2 and CYP2C11 in the liver. The drug has been approved for the chronic treatment of severe ulcerative colitis, a chronic inflammatory bowel disease. This study investigated the pharmacokinetics of tofacitinib in rats with dextran sulfate sodium (DSS)-induced ulcerative colitis. After 1-min of intravenous infusion of tofacitinib (10 mg/kg), the area under the plasma concentration-time curves from time zero to time infinity (AUC) of tofacitinib significantly increased by 92.3%. The time-averaged total body clearance decreased significantly by 47.7% in DSS rats compared with control rats. After the oral administration of tofacitinib (20 mg/kg), the AUC increased by 85.5% in DSS rats. These results could be due to decreased intrinsic clearance of the drug caused by the reduction of CYP3A1/2 and CYP2C11 in the liver and intestine of DSS rats. In conclusion, ulcerative colitis inhibited CYP3A1/2 and CYP2C11 in the liver and intestines of DSS rats and slowed the metabolism of tofacitinib, resulting in increased plasma concentrations of tofacitinib in DSS rats.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4353-4356
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• 2015

Background: Levofloxacin is an effective medication for second line Helicobacter pylori (H. pylori) eradication. However, limited studies have approved its use as an effective antibiotic in first line therapy. Dexlansoprazole is a new PPI and lacks of evidence in support of a role in H. pylori eradication. This study was designed to evaluate efficacy of levofloxacin-dexlansoprazole-based quadruple therapy for H. pylori eradication in Thailand. Materials and Methods: This prospective randomized control study was performed during June 2014 to December 2014. H. pylori infected gastritis patients were randomized to receive 7- or 14-day levofloxacin-dexlansoprazole based on quadruple therapy (levofloxacin 500 mg OD, dexlansoprazole 60 mg bid, clarithromycin MR 1000 mg OD, bismuth subsalicylate 1048 mg bid). CYP2C19 genotyping and antibiotic susceptibility tests were conducted for all patients. A 13C urea breath test was performed to confirm H. pylori eradication at least 4 weeks after treatment. Results: A total of 100 patients were enrolled, comprising 44 males and 56 females (mean age of 52.6 years). Eradication rate by PP analysis was 85.7% (42/49) with the 7-day regimen and 98% (48/49) with the 14-day regimen (85.7% vs 98%; p-value=0.059). ITT analysis was 84% and 96% with 7- and 14-day regimens, respectively (84% vs 96%; p-value=0.092). Antibiotic susceptibility testing demonstrated 35.1% resistance to metronidazole, 18.3% to clarithromycin, and 13.5% to levofloxacin. CYP2C19 genotyping revealed 54.1% RM, 34.7% IM and 11.2% PM. The 14-day regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and metronidazole H. pylori resistant strains. Moreover, the eradication rate was 96.6% in patients with CYP2C19 genotype RM. Conclusions: The 14-day levofloxacin-dexlansoprazole based quadruple therapy provides high H. pylori eradication regardless of CYP2C19 genotype, clarithromycin or dual clarithromycin and metronidazole resistant strains. This regimen could be use as an alternative first line therapy for H. pylori eradication in Thailand.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6507-6512
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• 2013

The purpose of this study was to evaluate the associations of CYP1A1 genetic polymorphisms with the risk of developing esophageal cancer (EC). A case-control study was carried out in a Chinese population in which 157 hospital based EC cases and 157 population based healthy controls with 1:1 match by age and sex were included. PCR based restriction fragment length polymorphisms (PCR-RFLP) were used to detect genotypes in case and control groups. For the CYP1A1 Ile/Val polymorphism, comparing with wild genotype Ile/Ile, both the heterozygote genotype Ile/Val and the combined variant genotype Ile/Val+Val/Val increased the risk of esophageal cancer (OR: 2.05, 95%CI: 1.19-3.54, OR: 1.86, 95%CI: 1.11-3.12). No significant association was found between the CYP1A1 MspI polymorphism and EC. According to analysis of combined genotypes, the TC/AG combined genotype which contained both variant alleles of these two polymorphisms increased the risk of developing EC (OR: 2.12, 95%CI: 1.16-3.85). Our results suggested that genetic polymorphisms of CYP1A1 may increase the susceptibility to EC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4549-4553
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• 2012

This study was designed to investigate the frequency of CYP2D6 polymorphisms and evaluate the association between genetic polymorphisms of CYP2D6 and tamoxifen therapeutic outcome in Thai breast cancer patients. We recruited 48 breast cancer patients who received adjuvant tamoxifen for evaluating CYP2D6 genetic polymorphisms using microarray-based technology. Associations between genotypes-phenotypes and disease free survival were analyzed. Median follow up time was 5.6 years. The mean age of the subjects was 50 years. The 3 common allelic frequencies were 43.8% ($^*10$), 36.5 ($^*1$) and 10.4% ($^*2$) which are related to extensive metabolizer (EM) and intermediate metabolizer (IM) with 70.8% and 29.2 %, respectively. No association between CYP2D6 genotypes and DFS was demonstrated. Nevertheless, exploratory analysis showed statistically significant shorter DFS in the IM group of post-menopause patients (HR, 6.85; 95%CI, 1.48-31.69; P=0.005). Furthermore, we observed statistically significant shorter DFS of homozygous $CYP2D6^*10$ when compared with heterozygous CYP2D6*10 and other genotypes (P=0.005). $CYP2D6^*10$ was the most common genotype in our subjects. Post-menopause patients with homozygous $CYP2D6^*10$ and IM have shorter DFS. To confirm this relationship, larger samples and comprehensively designed trials in Thailand are required.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.35 no.2
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• pp.185-190
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• 2002

This study was carried out to measure the in vitro interaction of trialkyltin with the microsomal monooxygenase (MFO) system of the clam, Coelomactra antiquata. Cytochrome P450 (CYP) level and 7-ethonvesorufin-O-deethylase (EROD) activity were invetigated in the microsome isolated from digestive gland of the clam (C. antiquata) exposed to tributyltin chloride (TBTC), bis-tributyltinoxide (TBTO) and triphenyltin chloride (TPTC). The specific contents of CYP in clam microsome exposedto 0.4 mM TBTC, TBTO and TPTC for 20 minutes were decreased 52, 72 and $40\%$, respectively, compared to control group. The EROD activities also were inhibited by exposure to TBTO ($92\%$) and TPTC ($85\%$) except for TBTC, The level of CYP and the EROD actintles were decreased according to the OTC exposure concentrations. The toxic effects on the level of CYP and the EROD activities were in order of TPTC>TBTC>TBTO in this study. The measurement of CYP level and EROD activity could be applied as a biomarker for environmental study.

• Parasites, Hosts and Diseases
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• v.51 no.2
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• pp.165-175
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• 2013

The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF.

• Clinical and Experimental Reproductive Medicine
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• v.33 no.2
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• pp.85-95
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• 2006

Objective: To investigate whether polymorphisms of gene encoding CYP1B1 is associated with the risk of endometriosis in Korean women. Methods: We investigated 199 patients with histopathologically confirmed endometriosis rAFS stage III/IV and 183 control group women who were surgically proven to have no endometriosis. The genetic distribution of four different CYP1B1 polymorphisms at $G^{119}-T$, $G^{432}-C$, $T^{449}-C$, and $A^{453}-G$ were analyzed by polymerase chain reaction(PCR) and restriction fragment length polymorphism of PCR products. Results: We found no overall association between each individual CYP1B1 genotype and the risk of endometriosis. The odds ratio of genotype GG/GC+GG/TC+TT/AA compared to GG/CC/CC/AA(reference) was calculated as 2.06 with a 95% confidence interval of 1.003~4.216. Conclusion: This results suggest that CYP1B1 genetic polymorphism may be associated with development of endometriosis in Korean women.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.194-199
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• 2002

Many oxidative metabolites of tetrahydrocannabinols (THCs), active components of marijuana, were pharmacologically active, and 11-hydroxy-THCs, 11-oxo-${\Delta}^8$-THC, 7-oxo-${\Delta}^8$-THC, 8$\beta$, 9$\beta$-epoxyhexahydrocannabinol (EHHC), 9$\alpha$, l0$\alpha$-EHHC and 3'-hydroxy-${\Delta}^9$-THC were more active than THC in pharmacological effects such as catalepsy, hypothermia and barbiturate synergism in mice. Cannabidiol (CBD), another major component, was biotransfomred to two novel metabolites, 6-hydroxymethyl-${\Delta}^9$-THC and 3-pentyl-6, 7, 7a, 8, 9, lla-hexahydro-I, 7-dihydroxy-7, 1O-dimethyldibenzo[b, d]oxepin (PHDO) through 8R, 9-epoxy-CBD and 85, 9-epoxy-CBD, respectively. Both metabolites exhibited some pharmacological effects comparable to d9 - THe. Cannabinol (CBN), the other major component, was mainly metabolized to ll-hydroxy-CBN by hepatic microsomes of animals including humans. The pharmacological effects of the metabolite were higher than those of CBN demonstrating that II-hydroxylation of CBN is metabolic activation pathway of the cannabinoid as is the case in THCs. Tolerance and reciprocal cross-tolerance developed to pharmacological effects d8 - THC and ll-hydroxy-d8-THC , and the magnitude of tolerance development produced by the metabolite was significantly higher than that by d8-THC. The results indicate that ll-hydroxy-d8-THC has an important role not only in the pharmacological effects but also its tolerance development of d8 - THe. THCs and their metabolites competed to the specific binding of CP-55, 940, an agonist of cannabinoid receptor, to synaptic membrane from bovine cerebral cortex. The Ki value of THCs and their metabolites were closely paralleled to their pharmacological effects in mice. A novel cytochrome P450 (cyp2c29) was purified and identified as a major enzyme responsible for the metabolic activation of d8-THC at the II-position in the mouse liver. cDNA of CYP2C29 was cloned from a mouse cDNA library and its sequence was determined. The oxidation mechanism of THC by cyp2c29 was proposed.