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Antioxidant enzymes in oligodendroglial brain tumors: association with proliferation, apoptotic activity and survival

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Summary

Purpose of the study was to investigate the relationship between antioxidant enzyme expression and clinicopathological features in oligodendroglial tumors. The expression of antioxidant enzymes and related proteins (AOEs),␣manganese superoxide dismutase (MnSOD), thioredoxin (Trx), thioredoxin reductase (TrxR) and gammaglutamylcysteine synthetase catalytic and regulatory subunits (GLCL-C and GLCL-R), was studied in 85 oligodendroglial tumors. The material included 71 primary (43 grade II and 28 grade III) and 14 recurrent (6 grade II and 8 grade III) tumors. Fifty-seven cases were pure oligodendrogliomas and 28 were mixed oligoastrocytomas. Immunoreactivity for MnSOD was found in 89%, Trx in 29%, TrxR in 76%, GLCL-C in 70% and GLCL-R in 68% of cases. Increased Trx expression was associated with higher tumor grade, cell proliferation and apoptosis (P=0.006, P=0.001 and P=0.003, Mann–Whitney test). Pure oligodendrogliomas showed more intense staining than oligoastrocytomas, especially for MnSOD (P=0.002, Mann–Whitney test). In the total series Trx was associated with poor prognosis in univariate survival analysis (P=0.0343, log-rank test) and furthermore in Cox multivariate analysis (P=0.009) along with age (P=0.002). The results suggest that the expression of Trx has a correlation to patient outcome and that there may be some association between AOEs, like MnSOD and Trx, and clinicopathological features of oligodendrogliomas.

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References:

  1. Kleihues P, Cavanee WK, (eds) 2000 Pathology and Genetics. Tumours of the Nervous System, World Health Organization Classification of Tumours Lyon International Agency for Research on Cancer

    Google Scholar 

  2. Reifenberger G, Louis DN, Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology J Neuropathol Exp Neurol 62 (2):111–126 2003

    PubMed  CAS  Google Scholar 

  3. Fortin D, Cairncross GJ, Hammond RR, Oligodendroglioma: an appraisal of recent data pertaining to diagnosis and treatment Neurosurgery 45(6):1279–1291 1999

    Article  PubMed  CAS  Google Scholar 

  4. Halliwell B, Reactive oxygen species in living systems: source, biochemistry, and role in human disease Am J Med 91(3C): 14S–22S 1991

    Article  PubMed  CAS  Google Scholar 

  5. Soini Y, Kahlos K, Napankangas U, Kaarteenaho-Wiik R, Saily M, Koistinen P, Paakko P, Holmgren A, Kinnula VL, Widespread expression of thioredoxin and thioredoxin reductase in non-small cell lung carcinoma Clin Cancer Res 7 (6):1750–1757 2001

    PubMed  CAS  Google Scholar 

  6. Powis G, Montfort WR, Properties and biological activities of thioredoxins Annu Rev Biophys Biomol Struct 30:421–455, 2001

    Article  PubMed  CAS  Google Scholar 

  7. Powis G, Kirkpatrick DL, Angulo M, Baker A: Thioredoxin redox control of cell growth and death and the effects of inhibitors. Chem Biol Interact 111–112: 23–34, 1998

    Google Scholar 

  8. Powis G, Oblong JE, Gasdaska PY, Berggren M, Hill SR, Kirkpatrick DL: The thioredoxin/thioredoxin reductase redox system and control of cell growth. Oncol Res 10–11 (6): 539–544, 1994

  9. Kinnula V, Crapo J, Superoxide dismutases in the lung and human lung diseases Am J Respir Crit Care Med 167: 1600–1619 2003

    Article  PubMed  Google Scholar 

  10. Church SL, Grant JW, Meese EU, Trent JM, Sublocalization of the gene encoding manganese superoxide dismutase (MnSOD/SOD2) to 6q25 by fluorescence in situ hybridization and somatic cell hybrid mapping Genomics 14 (3): 823–825 1992

    Article  PubMed  CAS  Google Scholar 

  11. Paunu N, Sallinen SL, Karhu R, Miettinen H, Sallinen P, Kononen J, Laippala P, Simola KO, Helen P, Haapasalo H, Chromosome imbalances in familial gliomas detected by comparative genomic hybridization Gene Chromosome Canc 29 4:339–346 2000

    Article  CAS  Google Scholar 

  12. Marklund SL, Westman NG, Lundgren E, Roos G, Copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues Can Res 42 5:1955–1961 1982

    CAS  Google Scholar 

  13. Li Y, Huang T-T, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ, Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase Nat Genet 11 4:376–381 1995

    Article  PubMed  CAS  Google Scholar 

  14. Carlsson LM, Jonnson J, Edlund T, Marklund SL, Mice lacking extracellular superoxide dismutase are more sensitive to hyperoxia Proc Natl Acad Sci USA 92 14:6264–6268 1995

    Article  PubMed  CAS  Google Scholar 

  15. Cobbs CS, Whisenhunt TR, Wesemann DR, Harkins LE, Van Meir EG, Samanta M, Inactivation of wild-type p53 protein function by reactive oxygen and nitrogen species in malignant glioma cells Can Res 63 24:8670–8673 2003

    CAS  Google Scholar 

  16. Kinnula V, Pietarinen-Runtti P, Raivio K, Kahlos K, Pelin K, Mattson K, Linnainmaa K, Manganese superoxide dismutase in human pleural mesotheliomas cell lines Free Rad Biol Med 21 4:527–532 1996

    Article  PubMed  CAS  Google Scholar 

  17. Kahlos K, Anttila S, Asikainen T, Kinnula K, Raivio KO, Mattson K, Linnainmaa K, Kinnula VL, Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma Am J Respir Cell Mol Biol 18 4:570–580 1998

    PubMed  CAS  Google Scholar 

  18. Kahlos K, Paakko P, Kurttila E, Soini Y, Kinnula VL, Manganese superoxide dismutase as a diagnostic marker for malignant pleural mesothelioma Br J Cancer 82 5:1022–1029 2000

    Article  PubMed  CAS  Google Scholar 

  19. Kahlos K, Soini Y, Paakko P, Saily M, Linnainmaa K, Kinnula VL, Proliferation, apoptosis, and manganese superoxide dismutase in malignant mesothelioma Int J Cancer 88 1:37–43 2000

    Article  PubMed  CAS  Google Scholar 

  20. Haapasalo H, Kylaniemi M, Paunu N, Kinnula VL, Soini Y, Expression of antioxidant enzymes in astrocytic brain tumors Brain Pathol 13 2:155–164 2003

    Article  PubMed  CAS  Google Scholar 

  21. Holmgren A, Björnstedt M, Thioredoxin and thioredoxin reductase Method Enzymol 252:199–208 1995

    Article  CAS  Google Scholar 

  22. Mustacich D, Powis G, Thioredoxin reductase Biochem J 346:1–8 2000

    Article  PubMed  CAS  Google Scholar 

  23. Sun QA, Wu Y, Zappacosta F, Jeang KT, Lee BJ, Hatfield DL, Gladyshev VN, Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases J Biol Chem 274 35:24522–24530 1999

    Article  PubMed  CAS  Google Scholar 

  24. Tew KD, Glutathione-associated enzymes in anticancer drug resistance Cancer Res 54(16):4313–4320 1994

    PubMed  CAS  Google Scholar 

  25. Zhang K, Mack P, Wong KP, Glutathione-related mechanisms in cellular resistance to anticancer drugs Int J Oncol 12(4):871–882 1998

    PubMed  CAS  Google Scholar 

  26. Dalton TP, Dieter MZ, Yang Y, Shertzer HG, Nebert DW, Knockout of the mouse glutamate cysteine ligase catalytic subunit (Gclc) gene: embryonic lethal when homozygous, and proposed model for moderate glutathione deficiency when heterozygous Biochem Biophys Res Commun 279 2: 324 2000

    Article  PubMed  CAS  Google Scholar 

  27. Järvinen K, Soini Y, Kahlos K, Kinnula VL, Overexpression of gamma-glutamylcysteine synthetase in human malignant mesothelioma Hum Pathol33(7):748–755 2002

    Article  PubMed  CAS  Google Scholar 

  28. Sallinen PK, Haapasalo HK, Visakorpi T, Helen PT, Rantala IS, Isola JJ, Helin HJ, Prognostication of astrocytomas patient survival by Ki-67 (MIB-1), PCNA and S-phase fraction using archival paraffin-embedded samples J Pathol 174(4):275–282 1994

    Article  PubMed  CAS  Google Scholar 

  29. Miettinen HE, Paunu N, Rantala I, Kalimo H, Paljärvi L, Helin H, Haapasalo H, Cell cycle regulators (p51, p53, pRb) in oligodendrocytic tumors: a study by novel tumor microarray technique J Neurooncol 55(1):29–37 2001

    Article  PubMed  CAS  Google Scholar 

  30. Zhang Y, Zhao W, Zhang H, Domann FE, Oberley H, Overexpression of copper zinc superoxide dismutase suppresses human glioma cell growth Cancer Res62(4):1205–1212 2002

    PubMed  CAS  Google Scholar 

  31. Church SL, Grant JW, Ridnour LA, Oberley LW, Swanson PE, Meltzer PS, Trent JM, Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells Proc Natl Acad Sci USA 90(7):3113–3117 1993

    Article  PubMed  CAS  Google Scholar 

  32. Liang BC, Ross DA, Greenberg HS, Meltzer PS, Trent JM, Evidence of allelic imbalance of chromosome 6 in human astrocytomas Neurology 44:533–536 1994

    PubMed  CAS  Google Scholar 

  33. Raffel J, Bhattacharyya AK, Gallegos A, Cui H, Einspahr JG, Alberts DS, Powis G, Increased expression of thioredoxin-1 in human colorectal cancer is associated with decreased patient survival J Lab Clin Med 142(1):46–51 2003

    Article  PubMed  CAS  Google Scholar 

  34. Hu J, Ma X, Lindner DJ, Karra S, Hofmann ER, Reddy SP, Kalvakolan DV, Modulation of p53 dependent gene expression and cell death through thioredoxin–thioredoxin reductase by Interferon-Retinoid combination Oncogene 20 31:4235–4248 2001

    Article  PubMed  CAS  Google Scholar 

  35. Cairncross G, MacDonald D, Ludwin S, Lee D, Cascino T, Buckner J, Fulton D, Dropcho E, Stewart D, Schold C Jr, et al. Chemotherapy for anaplastic oligodendroglioma National Cancer Institute of Canada Clinical Trials Group J Clin Oncol 12(10):2013–2021 1994

    PubMed  CAS  Google Scholar 

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Acknowledgements

Eila Pohjola, Reija Randen and Salla Kolmihaara are warmly thanked for their assistance. This study was financially supported by Medical Research Fund of Tampere University Hospital, Pirkanmaa Cancer Society, Cancer Society of Finland and Cancer Society of southwestern Finland.

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Authors and Affiliations

  1. Department of Pathology, Tampere University Hospital, Tampere, Finland

    Järvelä Sally, Paljärvi Leo & Haapasalo Hannu

  2. Department of Ophthalmology, Tampere University Hospital, Tampere, Finland

    Bragge Helena

  3. Department of Oncology, Tampere University Hospital, Tampere, Finland

    Paunu Niina

  4. Department of Orthopaedics and Traumatology, Tampere City Hospital, Tampere, Finland

    Järvelä Timo

  5. Department of Pathology, Kuopio University Hospital, Kuopio, Finland

    Paljärvi Leo

  6. Departments of Pathology, Turku and Helsinki University Hospitals, Turku and Helsinki, Finland

    Kalimo Hannu

  7. Department of Neurosurgery, Tampere University Hospital, Tampere, Finland

    Helén Pauli

  8. Department of Medicine, Division of Pulmonary Medicine, Helsinki University Hospital, Helsinki, Finland

    Kinnula Vuokko

  9. Department of Pathology, University of Oulu, Oulu, Finland

    Soini Ylermi

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  1. Järvelä Sally
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  2. Bragge Helena
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  3. Paunu Niina
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  4. Järvelä Timo
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Correspondence to Järvelä Sally.

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Sally, J., Helena, B., Niina, P. et al. Antioxidant enzymes in oligodendroglial brain tumors: association with proliferation, apoptotic activity and survival. J Neurooncol 77, 131–140 (2006). https://doi.org/10.1007/s11060-005-9030-z

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  • DOI: https://doi.org/10.1007/s11060-005-9030-z

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