• Title/Summary/Keyword: SULT1A1

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Effects of SULT1A1 Copy Number Variation on Estrogen Concentration and Tamoxifen-Associated Adverse Drug Reactions in Premenopausal Thai Breast Cancer Patients: A Preliminary Study

  • Charoenchokthavee, Wanaporn;Ayudhya, Duangchit Panomvana Na;Sriuranpong, Virote;Areepium, Nutthada
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1851-1855
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    • 2016
  • Tamoxifen is a pharmacological estrogen inhibitor that binds to the estrogen receptor (ER) in breast cells. However, it shows an estrogenic effect in other organs, which causes adverse drug reactions (ADRs). The sulfotransferase 1A1 (SULT1A1) enzyme encoded by the SULT1A1 gene is involved in estrogen metabolism. Previous research has suggested that the SULT1A1 copy number is linked with the plasma estradiol (E2) concentration. Here, a total of 34 premenopausal breast cancer patients, selected from the Thai Tamoxifen (TTAM) Project, were screened for their SULT1A1 copy number, plasma E2 concentration and ADRs. The mean age was $44.3{\pm}11.1years$, and they were subtyped as ER+/progesterone receptor (PR)+ (28 patients), ER+/PR- (5 patients) and ER-/PR- (1 patient). Three patients reported ADRs, which were irregular menstruation (2 patients) and vaginal discharge (1 patient). Most (33) patients had two SULT1A1 copies, with one patient having three copies. The median plasma E2 concentration was 1,575.6 (IQR 865.4) pg/ml. Patients with ADRs had significantly higher plasma E2 concentrations than those patients without ADRs (p = 0.014). The plasma E2 concentration was numerically higher in the patient with three SULT1A1 copies, but this lacked statistical significance.

SULT1A1 Arg213His Polymorphism and Lung Cancer Risk: a Meta-analysis

  • Liao, Shao-Guang;Liu, Lu;Zhang, Ying-Yi;Wang, Ying;Wang, Ya-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.579-583
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    • 2012
  • Background: The SULT1A1 Arg213His polymorphism is reported to be associated with lung cancer risk. However, this relationship remains controversial. For better understanding a meta-analysis was therefore performed. Methods: An extensive search was performed to identify all case-control studies investigating association between SULT1A1 Arg213His polymorphism and lung cancer risk. The strength was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95%CI). Results: A total of five publications covering 1,669 cases and 1,890 controls were included in this meta-analysis. No significant association between SULT1A1 Arg213His polymorphism and lung cancer risk was observed in overall comparisons in all genetic models (dominant model: OR=1.33, 95%CI=1.00-1.76, P=0.05; additive model: OR=1.30, 95%CI=0.93-1.81, P=0.12; recessive model: OR=1.21, 95%CI=0.89-1.66, P=0.23). However, on subgroup analysis, an elevated risk in mixed populations with variant His allele was revealed in the dominant model (OR=1.66, 95% CI=1.06-2.62, P=0.03). Furthermore, the SULT1A1 Arg213His polymorphism was associated with an increased risk of lung cancer in both females and males in the dominant model (females: OR=1.72, 95%CI=1.29-2.27, P=0.00; males: OR=1.46, 95%CI=1.19-1.78, P=0.00). No significant association between this polymorphism and different smoking status (smokers and non-smokers) and the other ethnicities (Asians and Caucasians) was shown. Conclusions: The results of this meta-analysis indicate that the SULT1A1 Arg213His polymorphism is not associated with lung cancer risk in Asians and Caucasians, but possible elevation for genotype (GA/AA) in mixed populations and males and females needs further investigation.

Molecular epidemiology and cancer susceptibility -Genetic polymorphisms and susceptibility to urothelial cancer-

  • Katoh, Takahiko
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.05a
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    • pp.21-22
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    • 2003
  • Arylamines are suspected to be the primary causative agent of urothelial cancer in tobacco smoke. In the human liver, arylamines are N-hydroxylated by a cytochrome P450 (CYP) 1A2-catalyzed reaction, which produces a substrate for O-esterification that can be catalyzed by N-acetylatransferases (NAT) or sulfotransferases (SULT). (omitted)

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Assessment of Biomarkers in Acetaminophen-Induced Hepatic Toxicity by siRNA

  • Kang, Jin-Seok;Yum, Young-Na;Kim, Joo-Hwan;Park, Sue-Nie
    • Biomolecules & Therapeutics
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    • v.17 no.4
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    • pp.438-445
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    • 2009
  • We investigated global gene expression from both mouse liver and mouse hepatic cell lines treated with acetaminophen (APAP) in order to compare in vivo and in vitro profiles and to assess the feasibility of the two systems. During our analyses of gene expression profiles, we picked up several down-regulated genes, such as the cytochrome P450 family 51 (Cyp51), sulfotransferase family cytosolic 1C member 2 (Sult1c2), 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1), and several genes that were up-regulated by APAP, such as growth arrest and DNA-damage-inducible 45 alpha (Gadd45a), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1) and zinc finger protein 688 (Zfp688). For validation of gene function, synthesized short interfering RNAs (siRNAs) for these genes were transfected in a mouse hepatic cell line, BNL CL.2, for investigation of cell viability and mRNA expression level. We found that siRNA transfection of these genes induced down-regulation of respective mRNA expression and decreased cell viability. siRNA transfection for Cyp51 and others induced morphological alterations, such as membrane thickening and nuclear condensation. Taken together, siRNA transfection of these six genes decreased cell viability and induced alteration in cellular morphology, along with effective inhibition of respective mRNA, suggesting that these genes could be associated with APAP-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity, for better understanding of its mechanism.

Modulation of Biotransformation Enzymes by Phytochemicals: Impact of Genotypes

  • Lampe Johanna W.
    • Proceedings of the Korean Society of Food Science and Nutrition Conference
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    • 2004.11a
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    • pp.65-70
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    • 2004
  • Modulation of biotransformation enzymes is one mechanism by which a diet high in fruits and vegetable may influence cancer risk. Inhibition of cytochrome P450s (CYP) and concomitant induction of conjugating enzymes are hypothesized to reduce the impact of carcinogens in humans. Thus, exposure to types and amounts of phytochemicals may influence disease risk. Like other xenobiotics, many classes of phytochemicals are rapodly conjugated with glutathione, glucuronide, and sulfate moieties and excreted in urine and bile. In humans, circulating phytochemical levels very widely among individuals even in response to controlled dietary interventions. Polymorphisms in biotransformation enzymes, such as the glutathione S-transferases (GST), UDP-glucuronosyltransferases (UGT), and sulfotransferases (SULT), may ocntribute to the variability in phytochemical clearance and efficacy; polymorphic enzymes with lower enzyme activity prolong the half-lives of phytochmicals in vivo. Isothiocyanates (ITC) in cruciferous vegetables are catalyzed by the four major human GSTs: however reaction velocities of the enzymes differ greatly. In some observational studies of cancer, polymorphisms in the GSTMI and GSTTI genes that result in complete lack of GSTM1-1 protein, respectively, confer greater protection from cruciferous vegetable in individuals with these genotypes. Similarly, we have shown in a controlled dietary trial that levels of GST-alpha-induced by ITC-are higher in GSTMI-null individuals exposed to cruciferous vegetablse. The selectivity of glucuronosyl conjugation of flavonoids is dependent both on flavonoid structure as well as on the UGI isozyme involved in its conjuagtion. The effects of UGI polymorphisms on flavonoid clearnace have not been examind; but polymorphisms affect glucuronidation of several drugs. Given the strong interest in the chemopreventive effects of flavonoids, systematic evaluation of these polymorphic UGTs and flavonoid pharmacokinetics are warranted. Overall, these studies suggest that for phytochemicals that are metabolized by, and affect activity of, biotransformation enzymes, interactions between genetic polymorphisms in the enzymes and intake of the compounds should be considered in studies of cancer risk. Genetic polymorphisms in biotransformation enzymes may account in prat for individual variation in metabolism of a wide range of phytochemicals and their ultimate impact on health.

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A Study on Manufacturing Technique and Alloy Characteristics of Bronze Mirrors from Jeollanam-do Region in the Three Kingdoms Period (전남지역 출토 삼국시대 청동거울의 합금 특성과 제작 방법 고찰)

  • Lee, Eun Ji
    • Journal of Conservation Science
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    • v.37 no.6
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    • pp.767-777
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    • 2021
  • This study analyzed the microstructures and chemical composition of three samples of bronze mirrors excavated in the Jeollanam-do region, particularly Goheung and Damyang. Under x-ray irradiation, the analysis results confirmed the broken parts and pores caused by cracks, casting, and corrosion. Major and minor elemental analysis were performed on three mirrors by Scanning electron microscopy (SEM) with Energy dispersive x-ray spectrometry (EDS) and Inductively coupled plasma mass spe ctrome try (ICP-MS). The re sult shows that the bronze mirrors containe d Cu-Sn-Pb alloys. Alpha phase and eutectic phase were observed in the microstructure, confirming that the casting was performed without additional heat treatment. Notably, Three bronze mirrors were made early Three Kingdoms period in Korea.

Effect of Glutathione S-Transferase Polymorphisms on the Antioxidant System (Glutathione S-Transferase 유전적 다형성이 항산화 체계에 미치는 영향)

  • Jeon, Gyeong-Im;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.6
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    • pp.708-719
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    • 2007
  • Glutathione S-transferase genotypes GSTT1, GSTM1 and GSTP1 were characterized in 104 healthy male and female subjects and compared with parameters of oxidative stress at the level of DNA and lipids, with antioxidant enzymes, and with plasma antioxidants in smokers and non.smokers. Of the 104 subjects studied, 57.4% were GSTT1 present and 47.6% were GSTM1 present. The GSTP1 polymorphisms a and b were represented as follows: a/a, 75.5%; a/b, 21.6%; b/b type, 2.9%. The GSTT1 null genotype was associated with decreased glutathione in erythrocytes and elevated lymphocytes DNA damage. GST-Px was higher in GSTT1 null compared with GSTT1 present type. The homozygous GSTP1 genotype was not associated with any antioxidant status or DNA damage. The difference in plasma ${\alpha}$-carotene and erythrocytes GSH-Px and GST activities between smokers and non-smokers was detected in the GSTT1 null genotype. Plasma ${\gamma}$-tocopherol and ${\beta}$-carotene decreased significantly in smokers having GSTM1 null genotype. When GSTT1 and GSTM1 were combined, plasma lycopene and erythrocyte GST were reduced in smokers in both null types of these genes. As for GSTP1 genotype, plasma ${\alpha}$-carotene and erythrocytes GSH-Px decreased significantly in smokers with GSTP1 b/b, while erythrocytes GSH-Px activities decreased in smokers with GSTP1 a/b. The different ${\beta}$-carotene level between smokers and non-smokers was seen with both GSTP1 a/a and a/b genotype. It seems that polymorphisms in the phase II metabolizing enzyme glutathione S-transferase may be important determinants of commonly measured biomarkers.

A Study on Dose Distribution around Fletcher-Suit Colpostat Containing Cs-137 Source by a Computer (컴퓨터 의한 Fletcher-Suit Colpostat 주변의 Cs-137의 선량분포에 관한 연구)

  • Kang Wee-Saing
    • Radiation Oncology Journal
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    • v.7 no.2
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    • pp.305-311
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    • 1989
  • Fletcher-Suit colpostat has an internal structure to reduce dose to bladder and rectum. Some programs were developed to calculate dose at any point in water in three dimension around the colpostat containing Cs-137 tube, to find the shielding effect to dose by the internal structure, and to draw isodose curves and iso-shielding effect curves. Computer was an IBM compatible AT with EGA card and language was MS-Basic V6.0, Material, shape and geometry of the strucure, tube and colpostat were considered in algorithm for calculation of dose. Dose rates per unit mg. Ra. eq. in water calculated by a program were stored in auxiliary memory devices and retrieved in another programs. Isodose curves on medial side shrinked. Dose distribution was not symmetric about a transverse axis bisecting the colpostat. Reduction of dose was more excessive on top side than on bottom. Iso-shielding effect curve showed that the shielding effect was higher on top side than on bottom, and that there was shielding effect over almost all area of medial side. Such results were related to both shifted position of tube in the colpostat and asymmetric distribution of active source in the tube. Maximum of shielding effect was $49\%$ on top side and $44\%$ on bottom side. The direction of iso-shielding effect curve was generally radial from the center of active source. In treatment planning using Fletcher-Suit colpostat, the internal structure should be considered to find precise doses to bladder and rectum, etc.

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A Study on the Funerary Mean of the Vertical Plate Armour from the 4th Century - Mainly Based on the Burial Patterns Shown by the Ancient Tombs No.164 and No.165 in Bokcheon-dong - (종장판갑(縱長板甲) 부장의 다양성과 의미 - 부산 복천동 164·165호분 출토 자료를 중심으로 -)

  • Lee, Yu Jin
    • Korean Journal of Heritage: History & Science
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    • v.44 no.3
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    • pp.178-199
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    • 2011
  • The ancient tombs found in Bokcheon-dong, Busan originate from the time between the $4^{th}$ and $5^{th}$ centuries, the period of the Three Nations. They are known as the tombs where the Vertical Plate Armour was mainly buried. In 2006, two units of the Vertical Plate Armour were additionally investigated in the tombs No.164 and No.165 which had been constructed at the end of the eastern slope near the hill of the group of ancient tombs in Bokcheon-dong. Throughout this study, the contents of the two units of the Vertical Plate Armour, whose preservation process has been completed, have been arranged, while the group of constructed ancient tombs in Bokcheon-dong from the $4^{th}$ century has been observed through the consideration of the burial pattern. The units of the Vertical Plate Armour from the tombs No.164 and No.165 can be classified as the IIa-typed armor showing the Gyeongju and Ulsan patterns, according to the attribute of the manufacturing technology. Also, they can be chronologically recorded as those from the early period of Stage II among the three stages regarding the chronological recording of the Vertical Plate Armour. While more than two units of the Vertical Plate Armour were buried in the largesized tomb on the top of the hill of the group of ancient tombs, one unit of the Vertical Plate Armour was buried in the small-sized tomb. By considering such a trend, it can be said that in the stage of burying the armor showing the Gyeongju and Ulsan patterns (I-type and IIa-type), different units of the Vertical Plate Armour were buried according to the size of the tomb. However, as the armor showing the Busan pattern (IIb-type) was settled, only one unit was buried. Meanwhile, the tombs No.164 and No.165 can be included in the wooden chamber tomb showing the Gyeongju pattern, which is a slender rectangular wooden chamber tomb with the aspect ratio of more than 1:3. However, according to the trend shown by the buried earthenware, it can be said that there seem to be common types and patterns shared with the earthenware which has been found in the area of Gimhae and is called the one showing the Geumgwan Gaya pattern. In other words, there seem to be close relationships between the subject tombs and the tomb No.3 in Gujeong-dong and the tomb No.55 in Sara-ri, Gyeongju, regarding the types of armor and tombs and the arrangement of buried artifacts. However, the buried earthenware shows a relationship with the areas of Busan and Gimhae. By considering the combined trend of the Gyeongju and Gimhae elements found in one tomb, it is possible to assume that the group of constructed ancient tombs in Bokcheon-dong used to be actively related with both areas. It has been thought that the Vertical Plate Armour used to be the exclusive property of the upper hierarchy until now, since it was buried in the large-sized tomb located on the top of the hill of the group of ancient tombs in Bokcheondong. However, as shown in case of the tombs No.164 and No.165, it has been verified that the Vertical Plate Armour was also buried in the small-sized tomb in terms of such factors as locations, sizes, the amount of buried artifacts and the qualitative aspect. Therefore, it is impossible to discuss the hierarchical characteristic of the tomb just based on the buried units of the Vertical Plate Armour. Also, it is difficult to assume that armor used to symbolize the domination of the military forces. The hierarchical characteristic of the group of constructed ancient tombs in Bokcheon-dong from the $4^{th}$ century can be verified according to the location and size of each tomb. As are sult, the re seem to be some differences regarding the buried units of the vertical plate armour. However, it would be necessary to carry out amore multilateral examination in order to find out whether the burial of the vertical plate armour could be regarded as the artifact which symbolizes the status or class of the deceased.