• Title/Summary/Keyword: genetic alteration

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Identification of Tumor Suppressor Genes on Chromosome 21 (제21번 염색체의 종양억제유전자 발굴)

  • Lee, Eung-Bae;Choi, Jin-Eun;Jang, Jin-Sung;Park, Jae-Yong
    • Journal of Chest Surgery
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    • v.42 no.2
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    • pp.141-147
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    • 2009
  • Background: We performed this study to identify the tumor suppressor genes located in the long arm of chromosome 21 in non-small cell lung cancer. Material and Method: The genes of USP25 in 21q11.2, NCAM2, ADAMTS1 in 21q21.2, and Claudin-8 (CLDN8), Claudin-17 (CLDN17) and TIAM1 in 21q22.1 were investigated for their gene expressions, genetic alterations and promoter methylation. Result: The expressions of CLDN8 and CLDN17 were significantly decreased in 7 (L132, H157, H358, H522, H1299, H1703 and HCC2108) of 13 cell lines, and the expression of ADAMTS1 was also significantly reduced in 6 cell lines (A549, SW900, H1299, H1373, H1703 and H1793). There were no genetic alterations by PCR-SSCP and cDNA cloning in the cell lines with a decreased gene. In the cell lines with a decreased gene expression, the mRNA expression was increased significantly with treatment of 5-Aza-CdR. Conclusion: These results suggest that the ADMTS1, CLDN8 and CLDN17 may act as tumor suppressor genes.

Geochemical Dispersion of Elements in Volcanic Wallrocks of Pyrophyllite Deposits in Milyang Area, Kyeongnam Province (밀양지역 납석광상 화산암질 모암에서의 원소들의 지구화학적 분산)

  • Oh, Dae-Gyun;Chon, Hyo-Taek
    • Economic and Environmental Geology
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    • v.26 no.3
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    • pp.337-347
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    • 1993
  • Mineralogical and geochemical studies on some pyrophyllite deposits in Milyang area, Kyeongnam Province (Milyang and Sungjin mine) were carried out in order to investigate dispersion patterns of chemical elements in altered volcanic wallrocks, and to interpret genetic environments of the pyrophyllite deposits. Cretaceous andesitic and tuffaceous rocks, and pyrophyllite ore specimens were collected from the dumps and drilling cores. Andesitic wallrocks were grouped as unaltered and altered rocks in the order of pyrophyllitization. Vertical dispersion patterns and relative mobilities of chemical elements in volcanic wallrocks were discussed. Geochemical environment in the Milyang area is characterized by the occurrence of boron minerals such as dumortierite coexisting with pyrophyllite ores, and tourmaline in granitic rocks. Unaltered andesitic rocks are mainly composed of plagioclase, pyroxene and hornblende, and were propylitized and saussuritized. Altered andesitic rocks are bleached and consist of quartz, sericite, pyrophyllite, kaolinite, chlorite and disseminated pyrite. Pyrophyllite ores are mainly composed of quartz, pyrophyllite, dumortierite, dissemianted pyrite and some diaspore. Enrichment of $SiO_2$, $Al_2O_3$, LOI (loss on ignition), As and Cr, and depletion of $K_2O$, $Na_2O$, CaO, MgO and total Fe are characteristic during alteration process. The REE patterns show that the pyrophyllite deposits could be originated from the continental margin volcanics. The $(La/Lu)_{cn}$ ratios of the pyrophyllite ores increase from 4.2~23.2 to 2.67~128.8 owing to strong acidic hydrothermal alteration. Vertical dispersion patterns of $Al_2O_3$, $K_2O$, $Na_2O$, CaO, MgO, $Fe_2O_3$ (total Fe), As, Au, Sb, Cr and Sr in the wallrocks show the location of orebodies. Particularly dispersion patterns of $Al_2O_3$ and Cr indicate the extension of orebodies. Anomalous distribution of Au, As and Sb in wallrocks shows potential for gold occurrence below the pyrophyllite deposits. Judging from the relative mobilities of elements in wallrocks, $Al_2O_3$ could be added from hydrothermal solution, and the silicified rone be formed from the excess of $SiO_2$.

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Epigenetic Mechanisms of Depression: Role of Histone Modification and DNA Methylation in BDNF Gene (우울증의 후성유전기전: BDNF 유전자의 히스톤 변형 및 DNA 메틸화의 역할)

  • Park, Sung Woo
    • Journal of Life Science
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    • v.28 no.12
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    • pp.1536-1544
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    • 2018
  • Depression is a common, serious, and recurring mental disorder. The pathogenesis of depression involves many factors such as environmental factor, genetic factor and alteration of structure and function in neurobiological systems. Increasing evidence supports that epigenetic alteration may be associated with depression. The epigenetics is explained as the mechanisms by which environmental factor causes changes in chromatin structure and alters gene expression without changing DNA base sequence. DNA methylation and histone modification involving histone acetylation and methylation are the main epigenetic mechanisms. Animal studies have shown that stressful environment such as early life stress can leave persistent epigenetic marks in the genome, which alter gene expression and influence neural and behavioral function through adulthood. A potentially important gene in depression is brain-derived neurotrophic factor (BDNF). BDNF plays a central role in depression and antidepressant action. In studies of the rodent, exposure to stress at prenatal, postnatal, and adult stages alters BDNF expression through histone modification and DNA methylation of the BDNF gene which results in anxiety and depressive-like behavior. This review discusses recent advances in the study of the epigenetic mechanisms that contribute to depression, particularly histone modification and DNA methylation of the BDNF gene, that may help in the development of new targets for depression treatment.

Alteration in Concentrations of Leptin and Insulin in Korean Cattle with Reproductive Disorders (번식장애 한우의 렙틴 및 인슐린 농도 변화)

  • Choe, Chang-Yong;Kang, Da-Won
    • Journal of Embryo Transfer
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    • v.23 no.3
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    • pp.189-195
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    • 2008
  • The objective of this study is to investigate the changes in concentrations of leptin and insulin in serum of Korean cattle (Hanwoo) with reproductive disorders and to examine the relationship among leptin, insulin, and body condition score (BCS). The concentration of leptin in serum of pregnant Hanwoo showed insignificant difference from that in serum of Hanwoo with reproductive disorder, such as repeat breeding, follicular cyst, corpus luteum cyst, ovarian atrophy, and feeble estrus (p>0.05). However, the concentrations of leptin and insulin in serum were changed with different BCS value. In emaciated Hanwoo (BCS $2.0\sim2.9$), they were significantly decreased compared to BCS $3.0\sim3.4$ (p<0.05). The leptin showed different genotypes with different BCS value. In BCS $2.0\sim2.9$, C/T genotype was expressed (83.3%) more than C/C (16.7%) or T/T (0%) genotype, whereas C/C genotype was expressed (62.5%) more than C/T (25.0%) or T/T (12.5%) genotype in BCS $3.5\sim4.0$. The insulin concentration in follicular fluid obtained from ovary with follicular cyst which has follicles having diameter of $25\sim40 mm$ was significantly higher (p<0.05) than those in normal follicle fluid which has follicles having diameter of $3\sim10 mm$. These results showed that concentration of leptin and insulin in serum were related to BCS value and follicular size and suggest that the changes in concentration of leptin and/or insulin in serum could be a potent biomarker for diagnosis of bovine reproductive disorder.

Targeting Cancer Metabolism - Revisiting the Warburg Effects

  • Tran, Quangdon;Lee, Hyunji;Park, Jisoo;Kim, Seon-Hwan;Park, Jongsun
    • Toxicological Research
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    • v.32 no.3
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    • pp.177-193
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    • 2016
  • After more than half of century since the Warburg effect was described, this atypical metabolism has been standing true for almost every type of cancer, exhibiting higher glycolysis and lactate metabolism and defective mitochondrial ATP production. This phenomenon had attracted many scientists to the problem of elucidating the mechanism of, and reason for, this effect. Several models based on oncogenic studies have been proposed, such as the accumulation of mitochondrial gene mutations, the switch from oxidative phosphorylation respiration to glycolysis, the enhancement of lactate metabolism, and the alteration of glycolytic genes. Whether the Warburg phenomenon is the consequence of genetic dysregulation in cancer or the cause of cancer remains unknown. Moreover, the exact reasons and physiological values of this peculiar metabolism in cancer remain unclear. Although there are some pharmacological compounds, such as 2-deoxy-D-glucose, dichloroacetic acid, and 3-bromopyruvate, therapeutic strategies, including diet, have been developed based on targeting the Warburg effect. In this review, we will revisit the Warburg effect to determine how much scientists currently understand about this phenomenon and how we can treat the cancer based on targeting metabolism.

Au-Ag Minerals and Genetic Environments from the Yeongdeog Gold-Silver Deposits, Korea (영덕(盈德) 금(金)-은광상(銀鑛床)에서 산출(産出)되는 금(金)-은광물(銀鑛物)과 광상(鑛床)의 생성환경(生成環境))

  • Lee, Hyun Koo;Yoo, Bong-Cheal;Kim, Sang Jung
    • Economic and Environmental Geology
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    • v.28 no.6
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    • pp.541-551
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    • 1995
  • The Yeongdeog gold-silver deposits at Jipum, Gyeongsangbugdo, is of a middle Paleogene $(45.52{\pm}1.02Ma)$ vein type, and is hosted in shale and sandstone of Cretaceous age. Based on mineral paragenesis, vein structure and mineral assemblages, the ore mineralization can be divided into two distinct depositional stages. The early stage is associated with base-metals such as pyrite, arsenopyrite (27.99~30.99 at%), hematite, rutile, pyrrhotite, sphalerite (10.53~18.42 FeS mole%), chalcopyrite and galena with wallrock alteration such as chlorite, sericite and pyrite. The late stage is characterized by the Au-Ag mineralization such as electrum, Ag-bearing tetrahedrite, freibergite, pyrargyrite, unidentified mineral, pyrite, sphalerite (1.08~5.57 FeS mole%), chalcopyrite and galena. Fluid inclusion data indicate that fluid temperatures and salinities range from 343 to $227^{\circ}C$ and from 8.3 to 5.7 wt% eq. NaCl in early stage, respectively. Temperatures and salinities of NaCl eq. wt% range from 299 to $225^{\circ}C$ and from 12.9 to 4.3 in late stage, respectively. They suggest that complex cooling histories were occured by the mixing of the fluids. Sulfur fugacity $(-logfs_2)$ deduced by mineral assemblages and composition ranges from 8.3 to 14.7 atm. in early stage, and from 8.8 to 14.5 atm. in late stage. It suggests that the mineralization was related to decrease of temperature in early stage and fluctuations of $fS_2$ with decrease of temperature in late stage. Sulfur and oxygen isotope compositions are 4.48~5.60‰ and 9.25~10.8% in early stage, and late stage is 4.84~7.00‰ and 5.7‰, respectively. It indicated that hydrothermal fluids may be magmatic origin with some degree of mixing of another water during paragenetic time.

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Detection of p53 Mutation in Colorectal Cancer Using PCR-SSCP and DHPLC (대장암에서 PCR-SSCP와 DHPLC를 이용한 p53 돌연변이의 검출)

  • Sang-Bum Park;Sang-Man Han;Youn-Hyoung Nam;Won-Cheoul Jang
    • Journal of the Korean Chemical Society
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    • v.47 no.5
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    • pp.460-465
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    • 2003
  • Structural alteration of p53 and overexpression of p53 protein are the most common genetic abnormalities in various kinds of human cancer. Mutations in the p53 tumor-suppressor gene are usually associated with an advanced development of colorectal cancer characterized by the transition from the adenoma to carcinoma stage. Mutations in exons 5-8 of the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) and denaturing high performance liquid chromatography(DHPLC). SSCP analysis detected 7 mutations(C13109>T) in 50 colorectal cancer samples(14%) at exon 5, and DHPLC analysis detected 7 mutations (C13109>T) and 2 mutation(C13202>A, C13204>G) in 50 colorectal cancer samples(18%) at exon 5. All of 9 mutations were proved by sequencing analysis. We conclude that DHPLC is a highly sensitive and specific method for p53 gene mutations.

BLEEDING CONTROL BY CONTINUOUS WOUND DRAINAGE OF ACTIVE BLEEDING SITES OF TEETH EXTRACTION WOUND IN A PATIENT WITH ADVANCED LIVER CIRRHOSIS : REPORT OF A CASE (중증 간경변증 환자에서 발치창 과도 출혈부의 지속적 배농술을 통한 지혈 : 증례보고)

  • Mo, Dong-Yub;Yoo, Jae-Ha;Choi, Byung-Ho;Kim, Ha-Rang;Lee, Chun-Ui;Ryu, Mi-Heon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.35 no.6
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    • pp.431-436
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    • 2009
  • There are five principal causes for excessive bleeding in the immediate postextraction phase ; (1) Vascular wall alteration (wound infection, scurvy, chemicals, allergy) (2) Disorders of platelet function (genetic defect, drug-aspirin, autoimmune disease) (3) Thrombocytopenic purpuras (radiation, leukemia), (4) Inherited disorders of coagulation (hemophilia, Christmas disease, vitamin deficiency, anticoagulation drug-heparin, coumarin). If the hemorrhage from postextraction wound is unusually aggressive, and then dehydration and airway problem are occurred, the socket must be packed with gelatine sponge(Gelfoam) that was moistened with thrombin and wound closure & pressure dressing are applied. The thrombin clots fibrinogen to produce rapid hemostasis. Gelatine sponges moistened with thrombin provide effective coagulation of hemorrhage from small veins and capillaries. But, in dental alveoli, gelatine sponges may absorb oral microorganisms and cause alveolar osteitis (infection). This is a case report of bleeding control by continuous rubber strip & iodoform gauze drainage (without gelfoam packing) of active bleeding infection sites of three teeth extraction wounds in a 46-years-old female patient with advanced liver cirrhosis.

Approaches to Improving Production Efficiencies of Transgenic Animals

  • Tojo, Hideaki
    • Proceedings of the KSAR Conference
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    • 2000.10a
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    • pp.7-8
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    • 2000
  • Transgenic animals are very useful for scientific, pharmaceutical, and agricultural purposes. In livestock, transgenic technology has been used forthe genetic alteration of farm animals, the production of human proteins inlarge quantities in the milk of transgenic farm animals, and the generation of animals with organs suitable for xenotransplantation. To date, the transfer of foreign genes into farm animals has been performed mainly by microinjection of DNA into the pronuclei of fertilized eggs. However, the overall success rate of transgenic animals in livestock so far has been disappointingly low, eg., the efficiency is 0∼5% in swine, and less than 1% in sheep and cattle, compared with the rate in mice where 5% microinjected develop into transgenic animals. Recently, McGreath et al. (2000) have succeeded in producing the gene targeted sheep by the use of nuclear transfer from cultured somatic cells transfected with a foreign gene in vitro. However, we may need plenty of time until currently employ this method for gene transfer to farm animals. We have been studying to exploit the method for improving production efficiencies of transgenic animals with emphasis of its application to farm animals. The present paper describes three approaches that we have made in our laboratory to improve production efficiencies of transgenic animals, based on the DNA microinjection method. 1. Co-injection of restriction enzyme with foreign DNA into the pronucleus for elevating production efficiencies of transgenic animals. 2. Efficient selection of transgenic mouse embryos using EGFP as a marker gene. 3. Phenotypes of tansgenic mice expressing WAP/hGH-CAG/EGFP fusion gene produced by selecting transgenic embryos. 4. Efficient site-specific integration of the transgene targeting an endogenous lox like site in early mouse embryos.

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Molecular Evaluation of DNMT3A and IDH1/2 Gene Mutation: Frequency, Distribution Pattern and Associations with Additional Molecular Markers in Normal Karyotype Indian Acute Myeloid Leukemia Patients

  • Ahmad, Firoz;Mohota, Rupali;Sanap, Savita;Mandava, Swarna;Das, Bibhu Ranjan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1247-1253
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    • 2014
  • Mutations in the DNMT3A and IDH genes represent the most common genetic alteration after FLT3/NPM1 in acute myeloid leukemia (AML). We here analyzed the frequency and distribution pattern of DNMT3A and IDH mutations and their associations with other molecular markers in normal karyotype AML patients. Fortyfive patients were screened for mutations in DNMT3A (R882), IDH1 (R132) and IDH2 (R140 and R172) genes by direct sequencing. Of the 45 patients screened, DNMT3A and IDH mutations were observed in 6 (13.3%) and 7 (15.4%), respectively. Patients with isolated DNMT3A mutations were seen in 4 cases (9%), isolated IDH mutations in 5 (11.1%), while interestingly, two cases showed both DNMT3A and IDH mutations (4.3%). Nucleotide sequencing of DNMT3A revealed missense mutations (R882H and R882C), while that of IDH revealed R172K, R140Q, R132H and R132S. Both DNMT3A and IDH mutations were observed only in adults, with a higher frequency in males. DNMT3A and IDH mutations were significantly associated with NPM1, while trends towards higher coexistence with FLT3 mutations were observed. This is the first study to evaluate DNMT3A/IDH mutations in Indian patients. Significant associations among the various molecular markers was observed, that highlights cooperation between them and possible roles in improved risk stratification.