• Title/Summary/Keyword: IDH

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Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review

  • Cho, Hee Jin;Koo, JaeHyung
    • BMB Reports
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    • v.54 no.12
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    • pp.601-607
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    • 2021
  • Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors (GPCRs). OR expression outside of the nose has functions distinct from odor perception, and may contribute to the pathogenesis of disorders including brain diseases and cancers. Glioma is the most common adult malignant brain tumor and requires novel therapeutic strategies to improve clinical outcomes. Here, we outlined the expression of brain ORs and investigated OR expression levels in glioma. Although most ORs were not ubiquitously expressed in gliomas, a subset of ORs displayed glioma subtype-specific expression. Moreover, through systematic survival analysis on OR genes, OR51E1 (mouse Olfr558) was identified as a potential biomarker of unfavorable overall survival, and OR2C1 (mouse Olfr15) was identified as a potential biomarker of favorable overall survival in isocitrate dehydrogenase (IDH) wild-type glioma. In addition to transcriptomic analysis, mutational profiles revealed that somatic mutations in OR genes were detected in > 60% of glioma samples. OR5D18 (mouse Olfr1155) was the most frequently mutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDH wild-type-specific mutation. Based on this systematic analysis and review of the genomic and transcriptomic profiles of ORs in glioma, we suggest that ORs are potential biomarkers and therapeutic targets for glioma.

Genetic Variation of Natural Populations of Schisandra nigra in Mt. Halla (격리된 입지환경에서 형성된 한라산 흑오미자 자생군락의 유전변이)

  • 이갑연;이석우;김세현;김판기;정동준;한상섭
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.3 no.1
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    • pp.30-36
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    • 2001
  • Schisandra nigra Max. has been cultivated far a medical use as well as food. It is an endemic species which has a unique habitat at the altitude of 600-1,400 m in Cheju island. In this study, three natural populations of S. nigra were investigated by using of starch-gel electrophoresis to determine the extent and distribution of genetic diversity. Except 2 monomorphic locus (Mdh-2 and Pgi-1), 4 of the 6 isozyme locus (Idh, Mdh-2, Mnr, and Pgi-2), verified from 4 isozymes, revealed polymorphism in the three populations of S. nigra. The mean number of allele per locus was 1.7 and the percentages of polymorphism loci were 38.9% at 95% level and 50% at 99% level respectively. The observed and estimated heterozygosities were 0.141 and 0.147 respectively. Although plants which were in the face of crisis and distributed in the restricted area, have been known to the very low degree of genetic variation, S. nigra showed higher genetic variation than others. Genetic variation was mostly allocated within population and individuals than that among populations. The result of Wright's F analysis estimates of $F_{IT}$ and $F_{IT}$ showed that S. nigra population revealed Hardy-Weinberg steady state.

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Genetic Variation of Several Isoenzymes in Pinus densiflora for. multicaulis (반송(Pinus densiflora for. multicaulis)의 몇 가지 동위효소(同位酵素)의 유전변이(遺傳變異))

  • Hwang, Jae Woo;Lee, Seok Woo
    • Journal of Korean Society of Forest Science
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    • v.85 no.3
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    • pp.409-415
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    • 1996
  • Isozyme variations in 4 enzyme systems in Pinus densiflora for. multicaulis in 31 individual trees collected throughout the country were studied by starch gel electrophoresis using haploid megagametophyte tissue to compare with those of Pinus densiflora. A minimum of 7 loci were found to code for isozymes of the enzyme systems. No variation was found at locus GOT-A; at the remaining 6 variable loci(GDH-A, GOT-B, GOT-C, IDH-A, LAP-,A, LAP-B) and 2 to 4 alleles were identified. We could not find any marker alleles to distinguish Pinus densiflora for. multicaulis from Pinus densiflora at the isozymes studied here. Allele frequency distributions at each loci were almost all the same as those of P. densiflora. The percentage of polymorphic loci(99% level), the number of alleles per locus, the observed and expected heterozygosities were 85.7, 2.3, 0.165 and 0.186%, respectively. The level of genetic diversity in Pinus densiflora for. multicaulis seemed to be less than that of P. densiflora.

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Glioblastoma Cellular Origin and the Firework Pattern of Cancer Genesis from the Subventricular Zone

  • Yoon, Seon-Jin;Park, Junseong;Jang, Dong-Su;Kim, Hyun Jung;Lee, Joo Ho;Jo, Euna;Choi, Ran Joo;Shim, Jin-Kyung;Moon, Ju Hyung;Kim, Eui-Hyun;Chang, Jong Hee;Lee, Jeong Ho;Kang, Seok-Gu
    • Journal of Korean Neurosurgical Society
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    • v.63 no.1
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    • pp.26-33
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    • 2020
  • Glioblastoma (GBM) is a disease without any definite cure. Numerous approaches have been tested in efforts to conquer this brain disease, but patients invariably experience recurrence or develop resistance to treatment. New surgical tools, carefully chosen samples, and experimental methods are enabling discoveries at single-cell resolution. The present article reviews the cell-of-origin of isocitrate dehydrogenase (IDH)-wildtype GBM, beginning with the historical background for focusing on cellular origin and introducing the cancer genesis patterned on firework. The authors also review mutations associated with the senescence process in cells of the subventricular zone (SVZ), and biological validation of somatic mutations in a mouse SVZ model. Understanding GBM would facilitate research on the origin of other cancers and may catalyze the development of new management approaches or treatments against IDH-wildtype GBM.

Inheritance and Linkage of Some Polymorphic Isozymes in Ginkgo biloba L. (은행나무의 몇가지 다형적(多形的) 동위효소(同位酵素)의 유전양식(遺傳樣式) 및 연관(連關))

  • Kwon, Hae-Yeun;Kim, Zin-Suh
    • Journal of Korean Society of Forest Science
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    • v.89 no.4
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    • pp.527-535
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    • 2000
  • Isozyme variants of 15 enzyme systems were analyzed in megagametophytes of Ginkgo biloba L. Five enzyme systems (ADH, G6PD, IDH, MPI, and UGPP) appeared to be monomorphic. Only 11 isozyme zones observed in 10 enzyme systems were polymorphic : ACON-A, FST-B, GDH-A, GOT-B, MDH-B, MDH-C, MNR-A, PGI-B, PGM-A, 6PGD-B and SKDH-B. The segregation ratio and heterogeneity at most polymorphic zones suggested that each isozyme zone was controlled by a single locus with codominant alleles, but significant deviation from 1 : 1 segregation was observed at MDH-B in pooled data. Three pairs of isozyme loci (ACON-A : MDH-B, GOT-B : PGI-B, and MNR-A : SKDH-B) were found to be weakly linked. Recombination frequencies between them ranged from 0.38 to 0.40 (p<0.05).

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Genetic Divergence of Two Types of Finespotted Flounder, Pleuronichthys cornutus, Distributed in the Japan Sea Area (일본 해역에 서식하고 있는 도다리, Pleuronichthys cornutus, 2형간의 유전적 분기)

  • PARK Jung-Youn;KIJIMA Akihiro;KANG Yong-Joo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.27 no.3
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    • pp.306-313
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    • 1994
  • In order to estimate the degree of genetic divergence between the two types of finespotted flounder, Pleuronichthys cornutus which is important commercially in Japan, isozyme analysis was carried out by starch gel electrophoresis. Twenty two loci coding for fourteen enzymes were scored in two types of finespotted flounder and three completely divergent loci (Acp, Idh-2 and Mdh-2), with no common alleles, were observed between these two types. Nei's genetic distance between two types was 0.46592. However, the expected average heterozygosity was 0.120 in type A (Hon meitagarei) and 0.095 in type B (Bake meitagarei) These results mean that the existence of two types of finespotted flounder was established in this study which may have had genetic divergence and the divergence time of these two types may have been about $2.3{\times}10^6$ years ago.

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INTERRELATIONSHIP BETWEEN VIRULENT CLONAL TYPES, SEROTYPES AND LEUKOTOXICITY OF KOREAN STRAINS OF A. ACTINOMYCETEMCOMITANS (한국인 Actinobacillus actinomycetemcomitans 균주의 특이 독성 clone형과 혈청형 및 백혈구독성과의 관계)

  • Ku, Young
    • Journal of Periodontal and Implant Science
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    • v.25 no.3
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    • pp.487-496
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    • 1995
  • Previous studies have demonstrated that not all A. actinomycetemcomitans produced significant level of leukotoxic factor and its leukotoxicity have associated with serotype and genetic variation. Our aim was to investigate on the interrelationship between serotype and leukotoxicity of an A. actinomycetemcomitans consisting of 13 clinically well characterized. Korean isolates and to evaluate if particular virulent clonal types of A. actinomycetemcomitans are associated with periodontal disease. For this study, 13 strains of A. actinomycetemcomitans from 6 patients with periodontal disease were isolated and identified by using a selective medium(tryptic soy agar supplemented with 10% serum, $75{\mu}g$ of bacitracin and $5{\mu}g$ of vancomycin per ml) in 10% C02 incubator for 3days with routine Gram staining, colony morphology and biochemical test..For serotyping, antisera were prepared from reference strains of 5 serotypes. (ATCC 29523,Y4, SUNY aB 67, IDH 781, IDH 1705) and then ammonium sulfate precipitation, immunoabsorption and indirect immunofluoroscent procedures were done. For analysis of leukotoxicity, sonic extract of A. actinomycetemcomitans exposed to PMN, and trypan blue was stained for counting the cell viability. Finally Southern blot analyses of genomic DNA digested with the restriction enzyme Tag I was done and the Southern blots were hybridized with the 530bp fragment, termed delta 530, originating from the ltx promoter of strain 652 and deleted from strain JP2. Also ltxA-3.1 and SC2 probe from strain JP2 were hybridized with genomic DNA fragments. Results reveal that strains isolated showed approximately equal proportions of 3 serotypes(b, d, e) and serotype b was not detected. 2 patients harbored 2 different serotypes in the same disease site. The prevalence of leukotoxic strain was 23% and there was no relationship between serotype, leukotoxicity and clinical observations. Especially virulent clonal types of Actinobacillus actinomycetemcomitan (JP2 strain) could not found. Further studies are necessary on the genetic polymorphism of leukotoxin and its relations to clinical status.

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THE RELATIONSHIP BETWEEN PERIODONTAL DISEASE SEVERITY AND Actinobacillus actinomycetemcomitans SEROTYPE & GENOTYPE DISTRIBUTION (Actinobacillus actinomycetemcomitans의 혈청형과 유전자형 분포가 치주질환 심도에 미치는 영향)

  • Kim, Eun-Gyoung;Kim, Sung-Jo;Choi, Jeom-Il
    • Journal of Periodontal and Implant Science
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    • v.24 no.3
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    • pp.541-560
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    • 1994
  • The present study was performed to evaluate the relationship between the serotype or the genotype of Actnobacillus actinomycetemcomitans (A. a.) and the severity of periodontal disease. Total 64 A. a. clinical isolates were sampled from 46 sites of 20 subjects classified into the group I (1 periodontally healthy subject, 2 gingivitis patients, 5 ealry adult periodontitis patients), group II (3 moderatelly adult periodontitis patients) and group III (1 advanced adult periodontitis patient, 8 RPP patients). Southern bolt hybridization (fingerprinting) patterns of the five reference strains, A. a. strain ATCC 29523 (serotype a), ATCC 29522 (Serotype b), ATCC 43719 (serotype c), IDH 781 (serotype d) and IDH 1705 (serotype e), were used as the five basic genotypic patterns (A, B, C, D, E). NT type was designated as one which did dnot represent any of those five basic types. The serotypes were determined by ELISA technique with the serum samples from pre-immunized rabbit. Based on subject-based analysis, it was noted that genotypes A and C, NT, and B, D, E were significantly related to the disease groups I, II, and III, respectively. It was also noted that both the serotypes a and c were significantly related to the disease group I and II, while serotypes were significantly related bm), and serotypes b and nd were frequently found in sites with severe attachment loss (LA>6mm). The results indicated that the significant relationship can be delineated beteen the genotypes and the serotypes of Acinobacillus actinomycetemcomitans and the periodontal disease severity. The results also indicated that genotyping can provide more detailed information on its relationship with the disease severity based on both the patient-based and the site-based analyses.

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Malignant Glioma with Neuronal Marker Expression : A Clinicopathological Study of 18 Cases

  • Kim, Hong Rye;Lee, Jae Jun;Lee, Jung-Il;Nam, Do Hyun;Suh, Yeon-Lim;Seol, Ho Jun
    • Journal of Korean Neurosurgical Society
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    • v.59 no.1
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    • pp.44-51
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    • 2016
  • Objective : Malignant gliomas with neuronal marker expression (MGwNM) are rare and poorly characterized. Increasingly diverse types of MGwNM have been described and these reported cases underscore the dilemmas in the classification and diagnosis of those tumors. The aim of this study is to provide additional insights into MGwNM and present the clinicopathological features of 18 patients. Methods : We reviewed the medical records of 18 patients diagnosed as MGwNM at our institute between January 2006 and December 2012. Macroscopic total resection was performed in 11 patients (61%). We evaluated the methylation status of $O^6$-methylguanine-DNA methyltransferase (MGMT) and expression of isocitrate dehydrogenase 1 (IDH-1) in all cases, and deletions of 1p and 19q in available cases. Results : The estimated median overall survival was 21.2 months. The median progression-free survival was 6.3 months. Six patients (33%) had MGMT methylation but IDH1 mutation was found in only one patient (6%). Gene analysis for 1p19q performed in nine patients revealed no deletion in six, 19q deletion only in two, and 1p deletion only in one. The extent of resection was significantly correlated with progression free survival on both univariate analysis and multivariate analysis (p=0.002 and p=0.013, respectively). Conclusion : In this study, the overall survival of MGwNM was not superior to glioblastoma. The extent of resection has a significant prognostic impact on progression-free survival. Further studies of the prognostic factors related to chemo-radio therapy, similar to studies with glioblastoma, are mandatory to improve survival.