• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.179-182
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• 2013

Human cytochrome P4502E1 (CYP2E1) is a well-conserved xenobiotic-metabolizing enzyme expressed in liver, kidney, nasal mucosa, brain, lung, and other tissues. CYP2E1 is inducible by ethanol, acetone, and other low-molecular weight substrates and may mediate development of chemically-mediated cancers. CYP2E1 polymorphisms alter the transcriptional activity of the gene. This study was conducted in order to investigate the allele frequency variation in different populations of Andhra Pradesh. Two hundred and twelve subjects belonging to six populations were studied. Genotype and allele frequency were assessed through TaqMan allelic discrimination (rs6413419) and polymerase chain reaction-sequencing (-1295G>C and -1055C>T) after DNA isolation from peripheral leukocytes. The data were compared with other available world populations. The SNP rs6413419 is monomorphic in the present study, -1295G>C and -1055C>T are less polymorphic and followed Hardy-Weinberg equilibrium in all the populations studied. The -1295G>C and -1055C>T frequencies were similar and acted as surrogates in all the populations. Analysis of HapMap populations data revealed no significant LD between these markers in all the populations. Low frequency of $CYP2E1^*c2$ could be useful in the understanding of south Indian population gene composition, alcohol metabolism, and alcoholic liver disease development. However, screening of additional populations and further association studies are necessary. The heterogeneity of Indian population as evidenced by the different distribution of $CYP2E1^*c2$ may help in understanding the population genetic and evolutionary aspects of this gene.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4155-4161
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• 2016

Biliary obstruction is a common clinical manifestation of various conditions, including extrahepatic cholangiocarcinoma. However, a screening test for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction is not yet available. According to the rationale that the biliary system plays a major role in lipid metabolism, biliary obstruction may interfere with lipid profiles in the body. Therefore, plasma lipidomics may help indicate the presence or status of disease in biliary obstruction suspected extrahepatic cholangiocarcinoma. This study aimed to use plasma lipidomics for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction. Plasma from healthy volunteers, patients with benign biliary obstruction extrahepatic cholangiocarcinoma, and other related cancers were used in this study. Plasma lipids were extracted and lipidomic analysis was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Lipid profiles from extrahepatic cholangiocarcinoma patients showed significant differences from both normal and benign biliary obstruction conditions, with no distinction between the latter two. Relative intensity of the selected lipid mass was able to successfully differentiate all extrahepatic cholangiocarcinoma samples from patient samples taken from healthy volunteers, patients with benign biliary obstruction, and patients with other related cancers. In conclusion, lipidomics is a non-invasive method with high sensitivity and specificity for identification of extrahepatic cholangiocarcinoma in patients with biliary obstruction.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.112-112
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• 2001

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine signaling pathways by enhancing ligand metabolism, altering hormone synthesis, down regulating receptor levels, and interfering with gene transcription. And TCDD-mediated gene transactivation via the AhR has been shown to be dependent upon estrogen receptor (ER) expression in human breast cancer cells. In the present study, we have examined the effect of natural estrogen, phytoestrognes and environmental estrogens on the regulation of CYP1A1 gene expression in MCF-7 human breast cancer cell line. that ER and AhR are co-expressed. pCYP1A1 -luc reporter gene was transiently transfected into MCF-7 cells. These cells were treated with various chemicals and then luciferase assay was carried out. 17be1a-estradiol significantly inhibited TCDD stimulated luciferase activity dose dependently and this inhibition was partially recovered by concomitant treatment of tamoxifen. 17beta-estradiol metabolites, 2-hydroxyestradiol and 16alpha-estriol resulted in less potent inhibitory effect than estradiol and synthetic estrogen, diethylstilbestrol (DES) showed no effect on CYP1A1 gene expression. This study demonstrated that estrogen down-regulated TCDD stimulated CYP1A1 expression via ER mediation. And we have found out that several flavonoids such as genistein, kaempferol, daidzein, naringenin, and alkylphenols such as nonylphenol, 4-octylphenol and resveratrol also inhibited TCDD induced CYP1A1 expression like estrogen.

• 한국가금학회:학술대회논문집
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• 한국가금학회 2005년도 제22차 정기총회 및 학술발표회
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• pp.31-43
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• 2005

Isoflavones are naturally occurring plant chemicals belonging to the 'phytoestrogen' class. The isoflavones are strikingly similar in chemical structure to natural estrogens. The phenolic ring is a key structural element of most compounds that bind to estrogen receptors. Dietary components that recently have received attention for their action as phytoestrogens are soy isoflavones. Soy products are the most significant dietary sources of isoflavones. Recently It is concerned clinical nutrition of isoflavone that is driven by reason of alternative sources of exogenous estrogen are constantly being needed. Estrogen therapy after the menopause offers protection from cardiovascular disease, reduces the extent of osteoporosis and relieves menopausal symptoms. Exogenous estrogen treatment is a fear of possible increased risk of developing breast cancer and because of side effects. Daily intake of soybean or soy food can affirmative effect to disease occurrence, that is based on mechanical investigation, experimental results of animals and human. Research into isoflavone is going on various field to relieve hormone - dependent disease such as cancer, menopausal symptom, cardiovascular disease and osteoporosis. Isoflavone is plenty in soybean meal, soy by-product, but only limited information is available on isoflavone efficacy into animal husbandry. Thus we conducted three experiments to investigate the effects of dietary isoflavone on productivities, antioxidative responses and bone metabolism in poultry. Dietary supplementation of isoflavone resulted in preventing the lipid oxidation of plasma and egg yolk. Dietary isoflavone improved bone development in egg-type growing chicks and broilers in terms of tibial strength. It was suggested that the proper use of feed additives such as isoflavone might provide means of improving antioxidative effect, skeletal strength, egg and eggshell quality.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6409-6413
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• 2012

The innate immune system coordinates the inflammatory response to pathogens. To do so, its cells must discriminate self from non-self utilizing receptors that identify molecules synthesized exclusively by microbes. Toll-like receptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, they have evolved to recognize conserved products unique to microbial metabolism. These include lipopolysaccharide (LPS), lipotechoic acids, and peptidoglycans (PGN). We show here that TLRs, including TLR2, are expressed on the THP-1 human leukemia cell line. Activation of TLR2 signaling in THP-1 by PGN induces the synthesis of various soluble factors and proteins including interleukin-$1{\beta}$, interleukin-8 and TNF-${\alpha}$ and apoptosis of THP-1 with PGN dose and time dependence. Moreover, in this study we show that PGN induces apoptosis of THP-1 cells in a TNF-${\alpha}$-dependent manner. These findings indicate that TLR2 signaling results in a cascade leading to tumor apoptosis and differentiation, which may suggest new clinical prospects using TLR2 agonists as cytotoxic agents in certain cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3461-3464
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• 2012

Methotrexate (MTX) is an important drug for the treatment of childhood acute lymphoblastic leukemia (ALL). However, related toxicity occurs in many organs which may cause interruption of treatment, morbidity, and mortality. Single nucleotide polymorphisms (SNPs) of dihydrofolate reductase (DHFR) and gamma glutamyl hydrolase (GGH) are known to alter their enzymatic activity and thus affect the metabolism of MTX and influence the effectiveness. Therefore, we hypothesized that genetic variations of DHFR and GGH genes may influence the risk of toxicity after high dose MTX. The study population comprised of 105 children with ALL who were treated according to the modified St Jude Total XV protocol. The patients received 2.5 or $5g/m^2$ of MTX for 5 doses during the consolidation phase. Genotyping of DHFR 829C>T and GGH-401C>T was performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The GGH-401CT and TT genotypes were associated with increased risk of leukopenia and thrombocytopenia after high dose MTX (OR 2.97, 95%CI; 1.24-7.13 and OR 4.02, 95%CI; 1.58-10.26). DHFR 829C>T was not associated with toxicity. In conclusion, the GGH-401CT and TT genotypes were found to increase the risk of severe leukopenia and thrombocytopenia after exposure to high dose MTX for childhood ALL therapy.

• Asian-Australasian Journal of Animal Sciences
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• 제16권3호
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• pp.435-444
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• 2003

In 1957, Schwarz and Foltz discovered that selenium (Se) was an essential trace mineral and nutritionists then started extensive studies to figure out the metabolic function of this element which has been called as toxic mineral. The discovery that glutathione peroxidase (GSH-Px) contained Se demonstrated a biochemical role for Se as an essential trace element. The major physiological function of Se containing GSH-Px is thought to maintain low levels of $H_2O_2$ and other hydroperoxides in the cell to prevent tissues from peroxidation damages. It is known that the GSH-Px activity is increased when animals were fed high dietary levels of Se. Chemical properties of Se have much in common with sulfur (S) therefore Se would follow the sulfur pathways in its metabolism in animal body. Two sources of Se are available for supplementation of Se in animal feed. Inorganic Se can also exist in selenide (-2), elemental (0), selenite (+4) and selenate (+6) oxidation state with other minerals. When sulfur in S containing amino acids is replaced by Se, organic Se can be made and named "eleno"prior to the name of S containing amino acid, i.e. selenomethionine. Selenium deficiency affects humans as well as animals and dysfunctions such as exudative diathesis, retained placenta, mastitis, liver necrosis, Keshan disease, numerous diseases and cancer. From several centuries ago, Se toxicity was recognized in various animal species and much of the current toxic Se levels has been established largely based upon the controlled toxicity studies used inorganic Se. Toxic effects of Se in animal result in reduced feed intake, growth retardation, ataxia, diarrhea, alopecia and sloughing of hooves. However, several experiments demonstrated that Se deficiencies or toxicities were varied by dietary Se levels and sources. Recent studies demonstrated that the incidence of colorectal and prostate cancer was reduced by approximately 50% when humans consumed 200 ${\mu}g$ of Se daily.

• Journal of Nutrition and Health
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• 제33권8호
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• pp.802-812
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• 2000

The purpose of this study was to examine the effect of resistant starch(RS) in hyperchlesterolemia and colon cancer. The subjects of this study was eight college women participating in the general starch diet(GSD) period for 5 days and resistant starch diet(RSD) period for 7 days. RSD contains 30g or the RS. On the last day of each program blood were collected. And for the last 3 days of each diet period, the amount of all the food consumed by the subjects and feces were collected. Food was measured to determine and compared the energy, protein and fat intakes. The amount of total cholesterol, HDL-cholesterol, LDL-cholesterol and volatile fatty acids in plasma and the amounts of bile acids in feces were measured by gas chromatography. The results obtained were as follows, Daily energy intake was higher in the RSD compared with the GSD, Protein and fat intakes were lower in the RSD compared with the compared with the GSD. Volatile fatty acid contents in plasma, the amounts of acetic acid, propionic acid and valeric acid were higher in the RSD compared with the GSD. The amounts of bile acids in feces, cholic acid, chenodeoxycholic acid and lithocholic acid were higher in the RSD compared with the GSD, But the amount of deoxycholic acid n the RSD period was significantly low. Secondary/primary ratios of bile acids was lower in the RSD compared with GSD, respectively. We speculate that , RS consumption decreases colonic mucosal proliferation as a result of the decreased formation of cytotoxic secondary bile acids. Thus, RS intakes may contribute the prevention of heart disease and colon cancer in humans. (Korean J Nutrition 33(8) : 802-812, 2000)

• 생명과학회지
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• 제19권6호
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• pp.705-710
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• 2009

Sodium butyrate (NaBt)는 장에서 탄수화물대사로부터 생겨나는 짧은 천연지방산 사슬로 다양한 인간 암세포들 에게서 강력한 항암효능을 나타냄이 보고된 바 있지만 자세한 기전은 아직 알려져 있지 않다. 이 논문에서 우리는 NaBt가 주요 세포부착분자이면서 종양억제인자의 일종인 E-cadherin의 발현을 세포-특이적으로 촉진하는 기전을 연구하였다. 또한 NaBt는 E-eadherin의 발현을 촉진하는 것으로 알려진 p21의 발현도 증가시켰지만, NaBt에 의하여 증가한 p21은 E-cadherin의 활성화와 관련이 없음이 밝혀졌다. 그 대신에 NaBt는 CCAAT-box를 통한 E-cadherin 유전자의 프로모터 활성을 증가시킴으로써 E-cadherin의 발현을 전사수준에서 촉진하는 것 같다. 이렇게 NaBt에 의하여 증가된 E-cadherin은 주로 세포간 접촉면에 위치하면서 Hep3B 세포를 더 분화된 형태로 유도하여 NaBt의 항암활성이 나타나는 것 같다.

• 대한유전성대사질환학회지
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• 제13권1호
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• pp.48-53
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• 2013

Tyrosinemia I (fumarylacetoacetate hydrolase deficiency) is an autosomal recessive inborn error of tyrosine metabolism that produces liver failure in infancy or a more chronic course of liver disease with cirrhosis, often complicated by hepatocellular carcinoma in childhood or early adolescence. We studied a 37-year-old woman with tyrosinemia I whose severe liver disease in infancy and rickets during childhood were resolved with dietary therapy. From 14 years of age, she resumed unrestricted diet with the continued presence of the biochemical features of tyrosinemia, yet maintained normal liver function. In adult years, she accumulated only a small amount of succinylacetone. Despite this evolution to a mild biochemical and clinical phenotype, she eventually developed hepatocellular carcinoma. Her fumarylacetoacetate hydrolase genotype consists of a splice mutation, IVS6-1G>T, and a novel missense mutation, p.Q279R. Studies of resected liver revealed the absence of hydrolytic activity and immunological expression of fumarylacetoacetate hydrolase in tumour. In the non-tumoral areas, however, 53% of normal hydrolytic activity and immunologically present fumarylacetoacetate hydrolase were found. This case demonstrates the high risk of liver cancer in tyrosinemia I even in a seemingly favorable biological environment. In this study of tyrosinemia I, Case 2 with negative succinylacetone accumulation and the recovery of acute liver failure was compared with Case 1. Diet restriction and NTBC treatment are crucial to prevent hepatocellular carcinoma until liver transplant can take place and cure the condition. Further studies are needed to examine cases where liver cancer did not result despite clinical symptoms/signs of tyrosinemia type I.