• Title/Summary/Keyword: GSTP

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Predictive Potential of Glutathione S-Transferase Polymorphisms for Prognosis of Osteosarcoma Patients on Chemotherapy

  • Zhang, Shai-Lin;Mao, Ning-Fang;Sun, Jun-Ying;Shi, Zhi-Cai;Wang, Bing;Sun, Yong-Jian
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2705-2709
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    • 2012
  • Objective: To evaluate the predictive value of glutathione S-transferase (GST) gene polymorphisms for the prognosis of osteosarcoma patients receiving chemotherapy. Methods: A total of 159 patients were included in our study between January 2005 and December 2007., with follow-up until January 2012. Genotyping was based upon the duplex polymerase-chain-reaction with the PCR-CTPP method. Results: At the time of diagnosis, 15.4% of the patients presented with metastasis, while 22.3% developed metastasis during follow-up. At the time of final analysis on January 2012, the median follow-up was 45.5 months. Patients with null GSTM1 and GSTT1 had a higher event free survival rate than non-null genotype, but no significant association was found between the two genotypes and prognosis of osteosarcoma. Individuals with GSTP1 Val/Val genotype tended to live shorter than with the IIe/IIe genotype, and we found a significantly higher risk of death from osteosarcoma (adjusted HR=2.35, 95% CI=1.13-4.85). Conclusion: The GSTP1 gene polymorphism may have an important role in the prognosis of osteosarcoma patients with chemotherapy. Further analyses with larger samples and more genes encoding metabolizing and DNA repair enzymes are warranted.

Effects of the Genetic Polymorphisms on Urinary Excretion of 1-Hydroxypyrene and 2-Naphthol (일반인구에서 유전자 다형성이 요중 1-hydroxypyrene 및 2-naphthol의 배설량에 미치는 영향)

  • Hwang Moon-Young;Cho Byung-Mann;Moon Seong-Bae
    • Journal of Environmental Science International
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    • v.14 no.5
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    • pp.499-511
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    • 2005
  • This study was performed to determine the effects of genetic polymorphisms, such as glutathione S-transferase ${\mu}1(GSTM1)$, glutathione S-transferase ${\Theta}1\;(GSTM1)$, glutathione S-transferase ${\pi}l (GSTP1)$, aryl hydrocarbon N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), cytochrome P450 1A1 (CYP1A1) on the concentrations of urinary 1-hydroxypyrene (1-OHP) and 2-naphthol in general population with no occupational exposure to polycyclic aromatic hydrocarbons (PAHs). Study subjects were 257 men who visited a health promotion center in Susan. A questionnaire was used to obtain detailed data about age, smoking, drinking, body fat mass, intake of fat etc. Urinary l-OHP and 2-naphthol concentration were analyzed by HPLC system with a fluorescence detector. A multiplex PCR method was used to identify the genotypes for GSTM1 and GSTT1. The polymorphisms of GSTP1, NAT2, CYP1A1 and CYP2E1 were determined by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Urinary 1-OHP concentration was higher in deleted genotype of GSTM1, increased as smoking and alcohol drinking increased. Urinary 2-naphthol concentration was also rely on the age and smoking. Neither genetic polymorphism nor drinking-related factors were significantly related to urinary 2-naphthol concentration. No significant relation was found between physical characteristics and concentrations of urinary PAHs metabolites in the subjects, but the geometric mean of urinary 1-OHP and 2-naphthol was higher in the group with higher value compared to median value. These data suggest that in general population occupationally not exposed to PAHs, urinary concentration of PAHs metabolites is influenced by smoking, alcohol drinking and deleted genotype of GSTM1 in 1-OHP and smoking in 2-naphthol.

Glulathione-S-transferases Gene Polymorphism in Prediction of Gastric Cancer Risk by Smoking and Helicobacter Pylori Infection Status

  • Jing, Chen;Huang, Zhi-Jie;Duan, Yu-Qin;Wang, Pei-Hong;Zhang, Ru;Luo, Ke-Shu;Xiao, Xin-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3325-3328
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    • 2012
  • Aim: To evaluate the association of glutathione S-transferases gene polymorphisms with the risk of gastric cancer, with reference to smoking and Helicobacter pylori infection. Methods: We conducted a 1:1 matched case-control study with 410 gastric cancer cases and 410 cancer-free controls. Polymorphisms of GSTM1, GSTT1 and GSTP1 were determined using PCR-CTPP. Results: The GSTM1 and GSTT1 null genotypes were significantly associated with the risk of gastric cancer after adjusting for potential confounding factors (OR=1.68, 95% CI=1.32-2.23 for null GSTM1, OR=1.73; 95% CI=1.24-2.13 for null GSTT1). The combination of null GSTM1 and null GSTT1 conferred an elevated risk (OR=2.54, 95% CI=1.55-3.39). However, no association was found for GSTP1 polymorphism The smoking modified the association of GSTM1 and GSTT1 null genotypes with the risk of gastric cancer. Conclusion: GSTM1 and GSTT1 null genotypes are associated with increased risk of gastric cancer, and smoking modifies the association.

A New Murine Liver Fibrosis Model Induced by Polyhexamethylene Guanidine-Phosphate

  • Kim, Minjeong;Hur, Sumin;Kim, Kwang H.;Cho, Yejin;Kim, Keunyoung;Kim, Ha Ryong;Nam, Ki Taek;Lim, Kyung-Min
    • Biomolecules & Therapeutics
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    • v.30 no.2
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    • pp.126-136
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    • 2022
  • Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

Establishment of Geospatial Schemes Based on Topo-Climatology for Farm-Specific Agrometeorological Information (농장맞춤형 농업기상정보 생산을 위한 소기후 모형 구축)

  • Kim, Dae-Jun;Kim, Soo-Ock;Kim, Jin-Hee;Yun, Eun-Jeong
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.21 no.3
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    • pp.146-157
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    • 2019
  • One of the most distinctive features of the South Korean rural environment is that the variation of weather or climate is large even within a small area due to complex terrains. The Geospatial Schemes based on Topo-Climatology (GSTP) was developed to simulate such variations effectively. In the present study, we reviewed the progress of the geospatial schemes for production of farm-scale agricultural weather data. Efforts have been made to improve the GSTP since 2000s. The schemes were used to provide climate information based on the current normal year and future climate scenarios at a landscape scale. The digital climate maps for the normal year include the maps of the monthly minimum temperature, maximum temperature, precipitation, and solar radiation in the past 30 years at 30 m or 270 m spatial resolution. Based on these digital climate maps, future climate change scenario maps were also produced at the high spatial resolution. These maps have been used for climate change impact assessment at the field scale by reprocessing them and transforming them into various forms. In the 2010s, the GSTP model was used to produce information for farm-specific weather conditions and weather forecast data on a landscape scale. The microclimate models of which the GSTP model consists have been improved to provide detailed weather condition data based on daily weather observation data in recent development. Using such daily data, the Early warning service for agrometeorological hazard has been developed to provide weather forecasts in real-time by processing a digital forecast and mid-term weather forecast data (KMA) at 30 m spatial resolution. Currently, daily minimum temperature, maximum temperature, precipitation, solar radiation quantity, and the duration of sunshine are forecasted as detailed weather conditions and forecast information. Moreover, based on farm-specific past-current-future weather information, growth information for various crops and agrometeorological disaster forecasts have been produced.

A Branch and Bound Algorithm for Solving a Capacitated Subtree of Tree Problem in Local Access Telecommunication Networks

  • Cho, Geon;Kim, Seong-Lyun
    • Journal of the Korean Operations Research and Management Science Society
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    • v.22 no.3
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    • pp.81-98
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    • 1997
  • Given a rooted tree T with profits and node demands, the capacitated subtree of a tree problem (GSTP) consists of finding a rooted subtree of maximum profit, subject to having total demand no larger than the given capacity H. We first define the so-called critical item for CSTP and find an upper bound on the optimal value of CSTP in O(n$^{2}$) time, where n is the number of nodes in T. We then present our branch and bound algorithm for solving CSTP and illustrate the algiruthm by using an example. Finally, we implement our branch-and-bound algorithm and compare the computational results with those for both CPLEX and a dynamic programming algorithm. The comparison shows that our branch-and-bound algorithm performs much better than both CPLEX and the dynamic programming algorithm, where n and H are the range of [50, 500] and [5000, 10000], respectively.

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BENZENE INDUCED CHROMOSOME ABERRATIONS AND THE ASSOCIATION WITH GENETIC POLYMORPHISM

  • Kim, Su-Young;Cho, Yoon-Hee;Jung, Eun-Jung;Park, Jung keun;Paek, Do-Myung;Chung, Hai-Won
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.66-66
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    • 2002
  • This study was done to examine the benzene induced chromosomal aberrations and also the influence of genetic polymorphism(GSTM1, GSTT1, GSTP1, NAT2, NQO1, CYP2E1 and CYP1A1) on the chromosomal aberrations. In total, 82 benezene exposed workers and 76 matched controls were examined.(omitted)

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Lack of Associations between Genetic Polymorphisms in GSTM1, GSTT1 and GSTP1 and Pancreatic Cancer Risk: A Multi-Institutional Case-Control Study in Japan

  • Yamada, Ikuhiro;Matsuyama, Masato;Ozaka, Masato;Inoue, Dai;Muramatsu, Yusuke;Ishii, Hiroshi;Junko, Ueda;Ueno, Makoto;Egawa, Naoto;Nakao, Haruhisa;Mori, Mitsuru;Matsuo, Keitaro;Nishiyama, Takeshi;Ohkawa, Shinichi;Hosono, Satoyo;Wakai, Kenji;Nakamura, Kozue;Tamakoshi, Akiko;Kuruma, Sawako;Nojima, Masanori;Takahashi, Mami;Shimada, Kazuaki;Yagyu, Kiyoko;Kikuchi, Shogo;Lin, Yingsong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.391-395
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    • 2014
  • Background: We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. Materials and Methods: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. The study population consisted of 360 patients and 400 control subjects, who were recruited from several medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk. Results: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 and GSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) for individuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1- present genotypes. No synergistic effects of smoking or GST genotypes were observed. Conclusions: Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study.

Molecular Links between Alcohol and Tobacco Induced DNA Damage, Gene Polymorphisms and Patho-physiological Consequences: A Systematic Review of Hepatic Carcinogenesis

  • Mansoori, Abdul Anvesh;Jain, Subodh Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4803-4812
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    • 2015
  • Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.

Genetic Polymorphisms of GSTM1 and GSTT1 Genes in Delhi and Comparison with other Indian and Global Populations

  • Sharma, Anita;Pandey, Arvind;Sardana, Sarita;Sehgal, Ashok;Sharma, Joginder K.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5647-5652
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    • 2012
  • The glutathione S-transferases (GSTs) are involved in the metabolism of many xenobiotics, including an array of environmental carcinogens, pollutants, and drugs. Genetic polymorphisms in these genes may lead to inter-individual variation in susceptibility to various diseases. In the present study, GSTM1 and GSTT1 polymorphisms were analysed using a multiplex polymerase chain reaction in 500 normal individuals from Delhi. The frequency of individuals with GSTM1 and GSTT1 null genotypes were 168 (33.6%) and 62 (12.4%) respectively, and 54(10.8%) were having homozygous null genotype for both the genes GSTM1 and GSTT1simultaneously. The studied population was compared with reported frequencies from other neighbouring state populations, as well as with those from other ethnic groups; Europeans, Blacks, and Asians. The prevalence of homozygous null GSTM1 genotype is significantly higher in Caucasians and Asians as compared to Indian population. The frequency of GSTT1 homozygous null genotypes is also significantly higher in blacks and Asians. We believe that due to large number of individuals in this study, our results are reliable estimates of the frequencies of the GSTM1, GSTT1 in Delhi. It would provide a basic database for future clinical and genetic studies pertaining to susceptibility and inconsistency in the response and/or toxicity to drugs known to be the substrates for GSTs.