Biopolym. Cell. 2003; 19(1):19-30.
Molecular mechanisms of astrocytic gliomas carcinogenesis
1Garifulin O. M., 1Dmitrenko V. V., 1Kavsan V. M.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


Basic genetic alterations which lead to forming the astocytic gliomas of grade II–IV are described in the review. The data concerning the genetic elements, participating in the malignant transformation of astocytic cells, are summarized. The molecular mechanisms of the arising de novo and developing of the secondary astrocytic tumors are analyzed. The molecular characteristics of carcinogenesis of different malignancy grades astrocytic gliomas are compared. The general and specific elements that determine the malignant progression of astrocytic gliomas are described.


[1] Zozulya YuP, Patsko YaV, Nikiforova GM. Epidemiology neuro cancer: current situation in Ukraine and abroad (literature review). Klin meditsina. 1999; 5(2):234-47.
[2] Olovnikov AM. [Principle of marginotomy in template synthesis of polynucleotides]. Dokl Akad Nauk SSSR. 1971;201(6):1496-9.
[3] Watson JD. Origin of concatemeric T7 DNA. Nat New Biol. 1972;239(94):197-201.
[4] Cech TR, Nakamura TM, Lingner J. Telomerase is a true reverse transcriptase. Biokhimiia. 1997; 62(11):1407-10.
[5] Meeker AK, Coffey DS, Telomerase: a promising marker of biological immortality of germ, stem and cancer cells. Biokhimiia. 1997; 62(11):1547-57.
[6] Morii K, Tanaka R, Onda K, Tsumanuma I, Yoshimura J. Expression of telomerase RNA, telomerase activity, and telomere length in human gliomas. Biochem Biophys Res Commun. 1997;239(3):830-4.
[7] Mokbel K, Ghilchik M. Re: Telomerase activity in human breast tumors. J Natl Cancer Inst. 1996;88(12):839-40.
[8] Hiyama E, Kodama T, Shinbara K, Iwao T, Itoh M, Hiyama K, Shay JW, Matsuura Y, Yokoyama T. Telomerase activity is detected in pancreatic cancer but not in benign tumors. Cancer Res. 1997;57(2):326-31.
[9] Brien TP, Kallakury BV, Lowry CV, Ambros RA, Muraca PJ, Malfetano JH, Ross JS. Telomerase activity in benign endometrium and endometrial carcinoma. Cancer Res. 1997;57(13):2760-4.
[10] Wollemann M. Biochemistry of brain tumors. University Park Press, 1974, 197 p.
[11] Liang BC, Hays L. Mitochondrial DNA copy number changes in human gliomas. Cancer Lett. 1996;105(2):167-73.
[12] Liang BC. Evidence for association of mitochondrial DNA sequence amplification and nuclear localization in human low-grade gliomas. Mutat Res. 1996;354(1):27-33.
[13] Oudard S, Boitier E, Miccoli L, Rousset S, Dutrillaux B, Poupon MF. Gliomas are driven by glycolysis: putative roles of hexokinase, oxidative phosphorylation and mitochondrial ultrastructure. Anticancer Res. 1997;17(3C):1903-11.
[14] Meixensberger J, Herting B, Roggendorf W, Reichmann H. Metabolic patterns in malignant gliomas. J Neurooncol. 1995;24(2):153-61.
[15] Subhash MN, Rao BS, Shankar SK. Changes in lactate dehydrogenase isoenzyme pattern in patients with tumors of the central nervous system. Neurochem Int. 1993;22(2):121-4.
[16] Boado RJ, Black KL, Pardridge WM. Gene expression of GLUT3 and GLUT1 glucose transporters in human brain tumors. Brain Res Mol Brain Res. 1994;27(1):51-7.
[17] Head MW, Corbin E, Goldman JE. Coordinate and independent regulation of alpha B-crystallin and hsp27 expression in response to physiological stress. J Cell Physiol. 1994;159(1):41-50.
[18] Hitotsumatsu T, Iwaki T, Fukui M, Tateishi J. Distinctive immunohistochemical profiles of small heat shock proteins (heat shock protein 27 and alpha B-crystallin) in human brain tumors. Cancer. 1996;77(2):352-61.
[19] Kato S, Morita T, Takenaka T, Kato M, Hirano A, Herz F, Ohama E. Stress-response (heat-shock) protein 90 expression in tumors of the central nervous system: an immunohistochemical study. Acta Neuropathol. 1995;89(2):184-8.
[20] Ichimura K, Schmidt EE, Miyakawa A, Goike HM, Collins VP. Distinct patterns of deletion on 10p and 10q suggest involvement of multiple tumor suppressor genes in the development of astrocytic gliomas of different malignancy grades. Genes Chromosomes Cancer. 1998;22(1):9-15.
[21] Louis DN. The p53 gene and protein in human brain tumors. J Neuropathol Exp Neurol. 1994;53(1):11-21.
[22] Sidransky D, Mikkelsen T, Schwechheimer K, Rosenblum ML, Cavanee W, Vogelstein B. Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature. 1992;355(6363):846-7.
[23] Ohgaki H, Watanabe K, Peraud A, Biernat W, von Deimling A, Yasargil MG, Yonekawa Y, Kleihues P. A case history of glioma progression. Acta Neuropathol. 1999;97(5):525-32.
[24] Ohgaki H, Sch?uble B, zur Hausen A, von Ammon K, Kleihues P. Genetic alterations associated with the evolution and progression of astrocytic brain tumours. Virchows Arch. 1995;427(2):113-8.
[25] James CD, Collins VP. Glial tumors. Molecular genetics of nervous system tumors. Eds A. J. Levine, H. H. Schmidek. New-York: Wiley-Liss press, 1993: 241-8.
[26] Weber RG, Sabel M, Reifenberger J, Sommer C, Oberstrass J, Reifenberger G, Kiessling M, Cremer T. Characterization of genomic alterations associated with glioma progression by comparative genomic hybridization. Oncogene. 1996;13(5):983-94.
[27] Nishizaki T, Ozaki S, Harada K, Ito H, Arai H, Beppu T, Sasaki K. Investigation of genetic alterations associated with the grade of astrocytic tumor by comparative genomic hybridization. Genes Chromosomes Cancer. 1998;21(4):340-6.
[28] Fults D, Pedone CA, Thomas GA, White R. Allelotype of human malignant astrocytoma. Cancer Res. 1990;50(18):5784-9.
[29] Sallinen SL, Sallinen P, Haapasalo H, Kononen J, Karhu R, Hel?n P, Isola J. Accumulation of genetic changes is associated with poor prognosis in grade II astrocytomas. Am J Pathol. 1997;151(6):1799-807.
[30] Hoang-Xuan K, Merel P, Vega F, Hugot JP, Cornu P, Delattre JY, Poisson M, Thomas G, Delattre O. Analysis of the NF2 tumor-suppressor gene and of chromosome 22 deletions in gliomas. Int J Cancer. 1995;60(4):478-81.
[31] Seizinger BR, Martuza RL, Gusella JF. Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma. Nature. 1986 Aug 14-20;322(6080):644-7.
[32] Louis DN. A molecular genetic model of astrocytoma histopathology. Brain Pathol. 1997;7(2):755-64. Review.
[33] Willert JR, Daneshvar L, Sheffield VC, Cogen PH. Deletion of chromosome arm 17p DNA sequences in pediatric high-grade and juvenile pilocytic astrocytomas. Genes Chromosomes Cancer. 1995;12(3):165-72.
[34] Koopmann J, Maintz D, Schild S, Schramm J, Louis DN, Wiestler OD, von Deimling A. Multiple polymorphisms, but no mutations, in the WAF1/CIP1 gene in human brain tumours. Br J Cancer. 1995;72(5):1230-3.
[35] Ono Y, Tamiya T, Ichikawa T, Matsumoto K, Furuta T, Ohmoto T, Akiyama K, Seki S, Ueki K, Louis DN. Accumulation of wild-type p53 in astrocytomas is associated with increased p21 expression. Acta Neuropathol. 1997;94(1):21-7.
[36] Rubio MP, von Deimling A, Yandell DW, Wiestler OD, Gusella JF, Louis DN. Accumulation of wild type p53 protein in human astrocytomas. Cancer Res. 1993;53(15):3465-7.
[37] Alderson LM, Castleberg RL, Harsh GR 4th, Louis DN, Henson JW. Human gliomas with wild-type p53 express bcl-2. Cancer Res. 1995;55(5):999-1001.
[38] Heldin CH. Structural and functional studies on platelet-derived growth factor. EMBO J. 1992;11(12):4251-9.
[39] Hermanson M, Funa K, Koopmann J, Maintz D, Waha A, Westermark B, Heldin CH, Wiestler OD, Louis DN, von Deimling A, Nist?r M. Association of loss of heterozygosity on chromosome 17p with high platelet-derived growth factor alpha receptor expression in human malignant gliomas. Cancer Res. 1996;56(1):164-71.
[40] B?gler O, Huang HJ, Cavenee WK. Loss of wild-type p53 bestows a growth advantage on primary cortical astrocytes and facilitates their in vitro transformation. Cancer Res. 1995;55(13):2746-51.
[41] Yahanda AM, Bruner JM, Donehower LA, Morrison RS. Astrocytes derived from p53-deficient mice provide a multistep in vitro model for development of malignant gliomas. Mol Cell Biol. 1995;15(8):4249-59.
[42] Hermanson M, Funa K, Hartman M, Claesson-Welsh L, Heldin CH, Westermark B, Nist?r M. Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res. 1992;52(11):3213-9.
[43] Satoh J, Kim SU. Cytokines and growth factors induce HSP27 phosphorylation in human astrocytes. J Neuropathol Exp Neurol. 1995;54(4):504-12.
[44] Pilkington GJ. Tumour cell migration in the central nervous system. Brain Pathol. 1994;4(2):157-66.
[45] Eibl RH, Pietsch T, Moll J, Skroch-Angel P, Heider KH, von Ammon K, Wiestler OD, Ponta H, Kleihues P, Herrlich P. Expression of variant CD44 epitopes in human astrocytic brain tumors. J Neurooncol. 1995;26(3):165-70.
[46] Ekstrand AJ, James CD, Cavenee WK, Seliger B, Pettersson RF, Collins VP. Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res. 1991;51(8):2164-72.
[47] Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS 3rd, Johnson BE, Skolnick MH. A cell cycle regulator potentially involved in genesis of many tumor types. Science. 1994;264(5157):436-40.
[48] Walker DG, Duan W, Popovic EA, Kaye AH, Tomlinson FH, Lavin M. Homozygous deletions of the multiple tumor suppressor gene 1 in the progression of human astrocytomas. Cancer Res. 1995;55(1):20-3.
[49] Rosenberg JE, Lisle DK, Burwick JA, Ueki K, von Deimling A, Mohrenweiser HW, Louis DN. Refined deletion mapping of the chromosome 19q glioma tumor suppressor gene to the D19S412-STD interval. Oncogene. 1996;13(11):2483-5.
[50] Rubio MP, Correa KM, Ueki K, Mohrenweiser HW, Gusella JF, von Deimling A, Louis DN. The putative glioma tumor suppressor gene on chromosome 19q maps between APOC2 and HRC. Cancer Res. 1994;54(17):4760-3.
[51] el-Azouzi M, Chung RY, Farmer GE, Martuza RL, Black PM, Rouleau GA, Hettlich C, Hedley-Whyte ET, Zervas NT, Panagopoulos K, et al. Loss of distinct regions on the short arm of chromosome 17 associated with tumorigenesis of human astrocytomas. Proc Natl Acad Sci U S A. 1989;86(18):7186-90.
[52] Fults D, Petronio J, Noblett BD, Pedone CA. Chromosome 11p15 deletions in human malignant astrocytomas and primitive neuroectodermal tumors. Genomics. 1992;14(3):799-801.
[53] Sonoda Y, Iizuka M, Yasuda J, Makino R, Ono T, Kayama T, Yoshimoto T, Sekiya T. Loss of heterozygosity at 11p15 in malignant glioma. Cancer Res. 1995;55(10):2166-8.
[54] Ueki K, Ono Y, Henson JW, Efird JT, von Deimling A, Louis DN. CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated. Cancer Res. 1996;56(1):150-3.
[55] Fischer U, Meltzer P, Meese E. Twelve amplified and expressed genes localized in a single domain in glioma. Hum Genet. 1996;98(5):625-8.
[56] He J, Olson JJ, James CD. Lack of p16INK4 or retinoblastoma protein (pRb), or amplification-associated overexpression of cdk4 is observed in distinct subsets of malignant glial tumors and cell lines. Cancer Res. 1995;55(21):4833-6.
[57] Matsuoka M, Tani K, Asano S. Interferon-alpha-induced G1 phase arrest mediated by the down-regulation of G1 cyclin-associated kinase activities in mouse macrophages. Blood. 1996; 88(10):539-43.
[58] Selleri C, Sato T, Del Vecchio L, Luciano L, Barrett AJ, Rotoli B, Young NS, Maciejewski JP. Involvement of Fas-mediated apoptosis in the inhibitory effects of interferon-alpha in chronic myelogenous leukemia. Blood. 1997;89(3):957-64.
[59] Dutcher J. Biological and antitumor activity of IFN. Oncol Biother Update. 1996; 1(11): 1-11.
[60] Welter C, Henn W, Theisinger B, Fischer H, Zang KD, Blin N. The cellular myb oncogene is amplified, rearranged and activated in human glioblastoma cell lines. Cancer Lett. 1990;52(1):57-62.
[61] Roberts WM, Douglass EC, Peiper SC, Houghton PJ, Look AT. Amplification of the gli gene in childhood sarcomas. Cancer Res. 1989;49(19):5407-13.
[62] Gerosa MA, Talarico D, Fognani C, Raimondi E, Colombatti M, Tridente G, De Carli L, Della Valle G. Overexpression of N-ras oncogene and epidermal growth factor receptor gene in human glioblastomas. J Natl Cancer Inst. 1989;81(1):63-7.
[63] Lang FF, Miller DC, Koslow M, Newcomb EW. Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors. J Neurosurg. 1994;81(3):427-36.
[64] H?bert CA, Baker JB. Interleukin-8: a review. Cancer Invest. 1993;11(6):743-50.
[65] Yamanaka R, Tanaka R, Saitoh T, Okoshi S. Cytokine gene expression on glioma cell lines and specimens. J Neurooncol. 1994;21(3):243-7.
[66] Sawaya RE, Yamamoto M, Gokaslan ZL, Wang SW, Mohanam S, Fuller GN, McCutcheon IE, Stetler-Stevenson WG, Nicolson GL, Rao JS. Expression and localization of 72 kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo. Clin Exp Metastasis. 1996;14(1):35-42.
[67] Rao JS, Yamamoto M, Mohaman S, Gokaslan ZL, Fuller GN, Stetler-Stevenson WG, Rao VH, Liotta LA, Nicolson GL, Sawaya RE. Expression and localization of 92 kDa type IV collagenase/gelatinase B (MMP-9) in human gliomas. Clin Exp Metastasis. 1996;14(1):12-8.
[68] Karlbom AE, James CD, Boethius J, Cavenee WK, Collins VP, Nordenskj?ld M, Larsson C. Loss of heterozygosity in malignant gliomas involves at least three distinct regions on chromosome 10. Hum Genet. 1993;92(2):169-74.
[69] Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997;15(4):356-62.
[70] Teng DH, Hu R, Lin H, Davis T, Iliev D, Frye C, Swedlund B, Hansen KL, Vinson VL, Gumpper KL, Ellis L, El-Naggar A, Frazier M, Jasser S, Langford LA, Lee J, Mills GB, Pershouse MA, Pollack RE, Tornos C, Troncoso P, Yung WK, Fujii G, Berson A, Steck PA, et al. MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer Res. 1997;57(23):5221-5.
[71] Wang SI, Puc J, Li J, Bruce JN, Cairns P, Sidransky D, Parsons R. Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res. 1997;57(19):4183-6.
[72] Bostr?m J, Cobbers JM, Wolter M, Tabatabai G, Weber RG, Lichter P, Collins VP, Reifenberger G. Mutation of the PTEN (MMAC1) tumor suppressor gene in a subset of glioblastomas but not in meningiomas with loss of chromosome arm 10q. Cancer Res. 1998;58(1):29-33.
[73] Chiariello E, Roz L, Albarosa R, Magnani I, Finocchiaro G. PTEN/MMAC1 mutations in primary glioblastomas and short-term cultures of malignant gliomas. Oncogene. 1998;16(4):541-5.
[74] Harada K, Nishizaki T, Ozaki S, Kubota H, Ito H, Sasaki K. Intratumoral cytogenetic heterogeneity detected by comparative genomic hybridization and laser scanning cytometry in human gliomas. Cancer Res. 1998;58(20):4694-700.
[75] Sugawa N, Ekstrand AJ, James CD, Collins VP. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci U S A. 1990;87(21):8602-6.
[76] Rollbrocker B, Waha A, Louis DN, Wiestler OD, von Deimling A. Amplification of the cyclin-dependent kinase 4 (CDK4) gene is associated with high cdk4 protein levels in glioblastoma multiforme. Acta Neuropathol. 1996;92(1):70-4.
[77] Maruno M, Yoshimine T, Muhammad AK, Ninomiya H, Kato A, Hayakawa T. Chromosomal aberrations detected by comparative genomic hybridization (CGH) in human astrocytic tumors. Cancer Lett. 1999;135(1):61-6.
[78] Watanabe K, Tachibana O, Sata K, Yonekawa Y, Kleihues P, Ohgaki H. Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol. 1996;6(3):217-23;
[79] von Deimling A, Louis DN, von Ammon K, Petersen I, Hoell T, Chung RY, Martuza RL, Schoenfeld DA, Ya?argil MG, Wiestler OD, et al. Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme. J Neurosurg. 1992;77(2):295-301.
[80] Biernat W, Kleihues P, Yonekawa Y, Ohgaki H. Amplification and overexpression of MDM2 in primary (de novo) glioblastomas. J Neuropathol Exp Neurol. 1997;56(2):180-5.
[81] Ono Y, Tamiya T, Ichikawa T, Kunishio K, Matsumoto K, Furuta T, Ohmoto T, Ueki K, Louis DN. Malignant astrocytomas with homozygous CDKN2/p16 gene deletions have higher Ki-67 proliferation indices. J Neuropathol Exp Neurol. 1996;55(10):1026-31.
[82] Mizuno M, Yoshida J, Sugita K, Inoue I, Seo H, Hayashi Y, Koshizaka T, Yagi K. Growth inhibition of glioma cells transfected with the human beta-interferon gene by liposomes coupled with a monoclonal antibody. Cancer Res. 1990;50(24):7826-9.
[83] Saxena A, Shriml LM, Dean M, Ali IU. Comparative molecular genetic profiles of anaplastic astrocytomas/glioblastomas multiforme and their subsequent recurrences. Oncogene. 1999;18(6):1385-90.
[84] Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature. 1996;379(6560):88-91.
[85] Goldman CK, Kim J, Wong WL, King V, Brock T, Gillespie GY. Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology. Mol Biol Cell. 1993;4(1):121-33.
[86] Gammeltoft S, Danielsen A, Frodin M. Insulin-like growth factors in the nervous system: evolution, fetal development, maintenance and tumor formation. The insulin-like growth factors and their regulatory proteins. Ed. D. LeRoith. New-York: Elsevier Science, 1994: 295-305.
[87] Glick RP, Unterman TG, Lacson R. Identification of insulin-like growth factor (IGF) and glucose transporter-1 and -3 mRNA in CNS tumors. Regul Pept. 1993;48(1-2):251-6.
[88] Sandberg AC, Engberg C, Lake M, von Holst H, Sara VR. The expression of insulin-like growth factor I and insulin-like growth factor II genes in the human fetal and adult brain and in glioma. Neurosci Lett. 1988;93(1):114-9.
[89] Trojan J, Blossey BK, Johnson TR, Rudin SD, Tykocinski M, Ilan J, Ilan J. Loss of tumorigenicity of rat glioblastoma directed by episome-based antisense cDNA transcription of insulin-like growth factor I. Proc Natl Acad Sci U S A. 1992;89(11):4874-8.
[90] Ambrose D, Resnicoff M, Coppola D, Sell C, Miura M, Jameson S, Baserga R, Rubin R. Growth regulation of human glioblastoma T98G cells by insulin-like growth factor-1 and its receptor. J Cell Physiol. 1994;159(1):92-100.
[91] Chotani MA, Chiu IM. Differential regulation of human fibroblast growth factor 1 transcripts provides a distinct mechanism of cell-specific growth factor expression. Cell Growth Differ. 1997;8(9):999-1013.
[92] Takahashi JA, Mori H, Fukumoto M, Igarashi K, Jaye M, Oda Y, Kikuchi H, Hatanaka M. Gene expression of fibroblast growth factors in human gliomas and meningiomas: demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues. Proc Natl Acad Sci U S A. 1990;87(15):5710-4.
[93] Morrison RS, Yamaguchi F, Saya H, Bruner JM, Yahanda AM, Donehower LA, Berger M. Basic fibroblast growth factor and fibroblast growth factor receptor I are implicated in the growth of human astrocytomas. J Neurooncol. 1994;18(3):207-16. Review.
[94] Yamaguchi F, Saya H, Bruner JM, Morrison RS. Differential expression of two fibroblast growth factor-receptor genes is associated with malignant progression in human astrocytomas. Proc Natl Acad Sci U S A. 1994;91(2):484-8.
[95] Myers RL, Chedid M, Tronick SR, Chiu IM. Different fibroblast growth factor 1 (FGF-1) transcripts in neural tissues, glioblastomas and kidney carcinoma cell lines. Oncogene. 1995;11(4):785-9.
[96] Mapstone T, McMichael M, Goldthwait D. Expression of platelet-derived growth factors, transforming growth factors, and the ros gene in a variety of primary human brain tumors. Neurosurgery. 1991;28(2):216-22.
[97] Wrann M, Bodmer S, de Martin R, Siepl C, Hofer-Warbinek R, Frei K, Hofer E, Fontana A. T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta. EMBO J. 1987;6(6):1633-6.
[98] Kuppner MC, Hamou MF, Sawamura Y, Bodmer S, de Tribolet N. Inhibition of lymphocyte function by glioblastoma-derived transforming growth factor beta 2. J Neurosurg. 1989;71(2):211-7.
[99] Nabioullin R, Sone S, Mizuno K, Yano S, Nishioka Y, Haku T, Ogura T. Interleukin-10 is a potent inhibitor of tumor cytotoxicity by human monocytes and alveolar macrophages. J Leukoc Biol. 1994;55(4):437-42.
[100] Nitta T, Hishii M, Sato K, Okumura K. Selective expression of interleukin-10 gene within glioblastoma multiforme. Brain Res. 1994;649(1-2):122-8.
[101] Kwaan HC. The plasminogen-plasmin system in malignancy. Cancer Metastasis Rev. 1992;11(3-4):291-311.
[102] Gladson CL, Pijuan-Thompson V, Olman MA, Gillespie GY, Yacoub IZ. Up-regulation of urokinase and urokinase receptor genes in malignant astrocytoma. Am J Pathol. 1995;146(5):1150-60.
[103] Murphy P, Hart DA. Modulation of plasminogen activator and plasminogen activator inhibitor expression in the human U373 glioblastoma/astrocytoma cell line by inflammatory mediators. Exp Cell Res. 1992;198(1):93-100.
[104] Go Y, Chintala SK, Mohanam S, Gokaslan Z, Venkaiah B, Bjerkvig R, Oka K, Nicolson GL, Sawaya R, Rao JS. Inhibition of in vivo tumorigenicity and invasiveness of a human glioblastoma cell line transfected with antisense uPAR vectors. Clin Exp Metastasis. 1997;15(4):440-6.
[105] Chintala SK, Sawaya R, Gokaslan ZL, Fuller G, Rao JS. Immunohistochemical localization of extracellular matrix proteins in human glioma, both in vivo and in vitro. Cancer Lett. 1996;101(1):107-14.
[106] Sehgal A, Boynton AL, Young RF, Vermeulen SS, Yonemura KS, Kohler EP, Aldape HC, Simrell CR, Murphy GP. Cell adhesion molecule Nr-CAM is over-expressed in human brain tumors. Int J Cancer. 1998;76(4):451-8.
[107] Reyes-Mugica M, Rieger-Christ K, Ohgaki H, Ekstrand BC, Helie M, Kleinman G, Yahanda A, Fearon ER, Kleihues P, Reale MA. Loss of DCC expression and glioma progression. Cancer Res. 1997;57(3):382-6.
[108] Schott B, Bennis S, Pourquier P, Ries C, Londos-Gagliardi D, Robert J. Differential over-expression of mdr1 genes in multidrug-resistant rat glioblastoma cell lines selected with doxorubicin or vincristine. Int J Cancer. 1993;55(1):115-21.
[109] Walther W, Stein U, Pfeil D. Gene transfer of human TNF alpha into glioblastoma cells permits modulation of mdr1 expression and potentiation of chemosensitivity. Int J Cancer. 1995;61(6):832-9.
[110] Newcomb EW, Cohen H, Lee SR, Bhalla SK, Bloom J, Hayes RL, Miller DC. Survival of patients with glioblastoma multiforme is not influenced by altered expression of p16, p53, EGFR, MDM2 or Bcl-2 genes. Brain Pathol. 1998;8(4):655-67.
[111] Lichtor T, Libermann TA. Coexpression of interleukin-1 beta and interleukin-6 in human brain tumors. Neurosurgery. 1994;34(4):669-72;
[112] Farias-Eisner R, Sherman MP, Aeberhard E, Chaudhuri G. Nitric oxide is an important mediator for tumoricidal activity in vivo. Proc Natl Acad Sci U S A. 1994;91(20):9407-11.
[113] Ludwig HC, Feiz-Erfan I, Bockermann V, Behnke-Mursch J, Schallock K, Markakis E. Expression of nitric oxide synthase isozymes (NOS I-III) by immunohistochemistry and DNA in situ hybridization. Correlation with macrophage presence, vascular endothelial growth factor (VEGF) and oedema volumetric data in 220 glioblastomas. Anticancer Res. 2000;20(1A):299-304.
[114] Strohman R. Epigenesis: the missing beat in biotechnology? Biotechnology (N Y). 1994;12(2):156-64.