In vivo models of primary brain tumors: Pitfalls and perspectives

Neuro-Oncology

Volumn 14, Issue 8, 2012, Pages 979-993

  Huszthy, Peter C ^a   Daphu, Inderjit ^a   Niclou, Simone P ^b   Stieber, Daniel ^b   Nigro, Janice M ^c   Sakariassen, Per O ^c   Miletic, Hrvoje ^a,c   Thorsen, Frits ^a   Bjerkvig, Rolf ^a,b  

^a UNIVERSITY OF BERGEN   (Norway)

^b LUXEMBOURG INSTITUTE OF HEALTH   (Luxembourg)

^c HAUKELAND UNIVERSITY HOSPITAL   (Norway)

Author keywords

animal models; brain tumor development

Indexed keywords

BRAIN TUMOR; CANCER CELL CULTURE; CENTRAL NERVOUS SYSTEM TUMOR; CHEMICAL CARCINOGENESIS; DISEASE COURSE; EXPERIMENTAL MODEL; EXPERIMENTAL NEOPLASM; GENETIC ENGINEERING; GENETIC MODEL; GLIOBLASTOMA; GLIOMA; HUMAN; IN VIVO STUDY; NONHUMAN; PRIMARY TUMOR; REVIEW; TUMOR BIOPSY; TUMOR CELL LINE; TUMOR MODEL; TUMOR XENOGRAFT;

ANIMALS; BRAIN NEOPLASMS; DISEASE MODELS, ANIMAL; GLIOBLASTOMA; HUMANS;

EID: 84864704674     PISSN: 15228517     EISSN: 15235866     Source Type: Journal    
DOI: 10.1093/neuonc/nos135     Document Type: Review

References (133)

1. Kerbel RS. What is the optimal rodent model for anti-tumor drug testing? Cancer Metastasis Rev. 1998;17(3):301-304.
2. Kerbel RS.Human tumor xenografts as predictive preclinicalmodels for anticancer drug activity in humans: better than commonly perceived-but they can be improved. Cancer Biol Ther. 2003;2(4 suppl 1):S134-S139.
3. Peterson JK, Houghton PJ. Integrating pharmacology and in vivo cancer models in preclinical and clinical drug development. Eur J Cancer. 2004;40(6):837-844.
4. Hesselager G, Holland EC. Using mice to decipher the molecular genetics of brain tumors. Neurosurgery. 2003;53(3):685-694; discussion 695.
5. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57-70.
6. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell. 2011;144(5):646-674.
7. Greene HS, Arnold HL, Jr. The homologous and heterologous transplantation of brain and brain tumors. J Neurosurg. 1945;2(4):315-331.
8. Greene HS. The significance of the heterologous transplantability of human cancer. Cancer. 1952;5(1):24-44.
9. Druckrey H, Ivankovic S, Preussmann R. [Selective induction of malignant tumors in the brain and spinal cord of rats by N-methyl-N-nitrosourea]. Z Krebsforsch. 1965;66:389-408.
10. Flanagan SP. 'Nude', a new hairless gene with pleiotropic effects in the mouse. Genet Res. 1966;8(3):295-309.
11. Ponten J, Macintyre EH. Long term culture of normal and neoplastic human glia. Acta Pathol Microbiol Scand. 1968;74(4):465-486.
12. Festing MF, May D, Connors TA, Lovell D, Sparrow S. An athymic nude mutation in the rat. Nature. 1978;274(5669):365-366.
13. Danks RA, Orian JM, Gonzales MF, et al. Transformation of astrocytes in transgenic mice expressing SV40 T antigen under the transcriptional control of the glial fibrillary acidic protein promoter. Cancer Res. 1995;55(19):4302-4310.
14. Holland EC, Hively WP, DePinho RA, Varmus HE. A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cellcycle arrest pathways to induce glioma-like lesions in mice. Genes Dev. 1998;12(23):3675-3685.
15. Holland EC, Celestino J, Dai C, Schaefer L, Sawaya RE, Fuller GN. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat Genet. 2000;25(1):55-57.
16. Engebraaten O, Hjortland GO, Hirschberg H, Fodstad O. Growth of precultured human glioma specimens in nude rat brain. J Neurosurg. 1999;90(1):125-132.
17. Reilly KM, Loisel DA, Bronson RT, McLaughlin ME, Jacks T. Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nat Genet. 2000;26(1):109-113.
18. Lee J, Kotliarova S, Kotliarov Y, et al. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell. 2006;9(5):391-403.
19. Krementz ET, Greene HS. Heterologous transplantation of human neural tumors. Cancer. 1953;6(1):100-110.
20. Jones TR, Bigner SH, Schold SC, Jr, Eng LF, Bigner DD. Anaplastic human gliomas grown in athymic mice. Morphology and glial fibrillary acidic protein expression. Am J Pathol. 1981;105(3):316-327.
21. Thomas DGT, Graham DI. Brain Tumours: Scientific Basis, Clinical Investigation, and Current Therapy. London/Boston: Butterworth; 1980, xiv, 382 p.
22. Peterson DL, Sheridan PJ, Brown WE, Jr. Animal models for brain tumors: historical perspectives and future directions. J Neurosurg. 1994;80(5):865-876.
23. Barth RF, Kaur B. Rat brain tumor models in experimental neurooncology: The C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas. J Neurooncol. 2009;94(3):299-312.
24. Li A, Walling J, Kotliarov Y, et al. Genomic changes and gene expression profiles reveal that established glioma cell lines are poorly representative of primary human gliomas. Mol Cancer Res. 2008;6(1):21-30.
25. Sibenaller ZA, Etame AB, Ali MM, et al. Genetic characterization of commonly used glioma cell lines in the rat animal model system. Neurosurg Focus. 2005;19(4):E1.
26. De Witt Hamer PC, Van Tilborg AA, Eijk PP, et al. The genomic profile of human malignant glioma is altered early in primary cell culture and preserved in spheroids. Oncogene. 2008;27(14):2091-2096.
27. Ernst A, Hofmann S, Ahmadi R, et al. Genomic and expression profiling of glioblastoma stem cell-like spheroid cultures identifies novel tumorrelevant genes associated with survival. Clin Cancer Res. 2009;15(21):6541-6550.
28. Mahesparan R, Read TA, Lund-Johansen M, Skaftnesmo KO, Bjerkvig R, Engebraaten O. Expression of extracellular matrix components in a highly infiltrative in vivo glioma model. Acta Neuropathol. 2003;105(1):49-57.
29. Bigner DD, Laerum OD, Rajewsky MF. International Union against Cancer. Biology of Brain Tumors. Geneva: International Union Against Cancer; 1978, 209 p.
30. Neuwelt EA, Barnett P, Barranger J, McCormick C, Pagel M, Frenkel E. Inability of dimethyl sulfoxide and 5-fluorouracil to open the bloodbrain barrier. Neurosurgery. 1983;12(1):29-34.
31. Schold SC, Jr, Friedman HS, Bigner DD. Therapeutic profile of the human glioma line D-54 MG in athymic mice. Cancer Treat Rep. 1987;71(9):849-850.
32. Schold SC, Jr, Friedman HS, Bjornsson TD, Bigner DD. Treatment of human glioma and medulloblastoma tumor lines in athymic mice with diaziquone and diaziquone-based drug combinations. Cancer Res. 1984;44(6):2352-2357.
33. Schold SC, Jr, Bigner DD. Treatment of five subcutaneous human glioma tumor lines in athymic mice with carmustine, procarbazine, and mithramycin. Cancer Treat Rep. 1983;67(9):811-819.
34. Eyre HJ, Eltringham JR, Gehan EA, et al. Randomized comparisons of radiotherapy and carmustine versus procarbazine versus dacarbazine for the treatment of malignant gliomas following surgery: A Southwest Oncology Group Study. Cancer Treat Rep. 1986;70(9): 1085-1090.
35. Bullard DE, Schold SC, Jr, Bigner SH, Bigner DD. Growth and chemotherapeutic response in athymic mice of tumors arising from human gliomaderived cell lines. J Neuropathol Exp Neurol. 1981;40(4):410-427.
36. Edwards MS, Levin VA, Wilson CB. Brain tumor chemotherapy: An evaluation of agents in current use for phase II and III trials. Cancer Treat Rep. 1980;64(12):1179-1205.
37. Chamberlain MC, Prados MD, Silver P, Levin VA. A phase II trial of oral melphalan in recurrent primary brain tumors. Am J Clin Oncol. 1988;11(1):52-54.
38. Dinapoli RP, Brown LD, Arusell RM, et al. Phase III comparative evaluation of PCNU and carmustine combined with radiation therapy for high-grade glioma. J Clin Oncol. 1993;11(7):1316-1321.
39. Hambardzumyan D, Amankulor NM, Helmy KY, Becher OJ, Holland EC. Modeling adult gliomas using RCAS/t-va technology. Transl Oncol. 2009;2(2):89-95.
40. Hambardzumyan D, Parada LF, Holland EC, Charest A. Genetic modeling of gliomas in mice: new tools to tackle old problems. Glia. 2011;59(8):1155-1168.
41. McLendon R, Friedman A, Bigner D, et al. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455(7216):1061-1068.
42. Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321(5897): 1807-1812.
43. Cortese Hassett AL, Locker JD, Kunz HW, Gill TJ, 3rd. Molecular analysis of MHC-linked genes affecting growth and development. Transplant Proc. 1989;21(1 Pt 1):563-564.
44. Mohr U, Rittinghausen S, Takenaka S, Ernst H, Dungworth DL, Pylev LN. Pathology of tumours in laboratory animals. Tumours of the lower respiratory tract and pleura in the rat. IARC Sci Publ. 1990;(99):275-299.
45. Ausman JI, Shapiro WR, Rall DP. Studies on the chemotherapy of experimental brain tumors: Development of an experimental model. Cancer Res. 1970;30(9):2394-2400.
46. Berens ME, Giese A, Shapiro JR, Coons SW. Allogeneic astrocytoma in immune competent dogs. Neoplasia. 1999;1(2): 107-112.
47. Ernestus RI, Wilmes LJ, Hoehn-Berlage M. Identification of intracranial liqor metastases of experimental stereotactically implanted brain tumors by the tumor-selective MRI contrast agent MnTPPS. Clin Exp Metastasis. 1992;10(5):345-350.
48. Gavin PR, Kraft SL, Wendling LR, Miller DL. Canine spontaneous brain tumors-a large animal model for BNCT. Strahlenther Onkol. 1989;165(2-3):225-228.
49. Dagle GE, Zwicker GM, Renne RA. Morphology of spontaneous brain tumors in the rat. Vet Pathol. 1979;16(3):318-324.
50. Schmidek HH, Nielsen SL, Schiller AL, Messer J. Morphological studies of rat brain tumors induced by N-nitrosomethylurea. J Neurosurg. 1971;34(3):335-340.
51. Druckrey H, Landschutz C. [Transplacental and neonatal carcinogenesis by ethylnitrosobiuret (ENBU) in BD IX-rats]. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1971;76(1):45-58.
52. Ivankovic S, Druckrey H. [Transplacental induction of malignant tumors of the nervous system. I. Ethyl-nitroso-urea (ENU) in BD IX rats]. Z Krebsforsch. 1968;71(4):320-360.
53. Swenberg JA, Koestner A, Wechsler W. The induction of tumors of the nervous system in rats with intravenous methylnitrosourea (MNU). J Neuropathol Exp Neurol. 1971;30(1):122.
54. Lantos PL, Pilkington GJ. Neuroblasts in cerebral tumors induced by ethylnitrosourea in rats. A fine structrual study. Virchows Arch B Cell Pathol. 1977;25(3):243-259.
55. Laerum OD, Rajewsky MF. Neoplastic transformation of fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. J Natl Cancer Inst. 1975;55(5):1177-1187.
56. Wechsler W, Ramadan MA, Pfeiffer SE. Morphologic and biochemical characteristics of transplantable neurogenic tumors induced by N-ethyl-N-nitrosourea in inbred BD IX rats. J Natl Cancer Inst. 1979;62(4):811-817.
57. Oda H, Zhang S, Tsurutani N, et al. Loss of p53 is an early event in induction of brain tumors in mice by transplacental carcinogen exposure. Cancer Res. 1997;57(4):646-650.
58. Samkange-Zeeb F, Schlehofer B, Schuz J, et al. Occupation and risk of glioma, meningioma and acoustic neuroma: results from a German case-control study (interphone study group, Germany). Cancer Epidemiol. 2010;34(1):55-61.
59. Samanic CM, De Roos AJ, Stewart PA, Rajaraman P, Waters MA, Inskip PD. Occupational exposure to pesticides and risk of adult brain tumors. Am J Epidemiol. 2008;167(8):976-985.
60. Benda P, Lightbody J, Sato G, Levine L, Sweet W. Differentiated rat glial cell strain in tissue culture. Science. 1968;161(839):370-371.
61. Parsa AT, Chakrabarti I, Hurley PT, et al. Limitations of the C6/Wistar rat intracerebral glioma model: Implications for evaluating immunotherapy. Neurosurgery. 2000;47(4):993-999; discussion 999-1000.
62. Resnicoff M, Sell C, Rubini M, et al. Rat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumors. Cancer Res. 1994;54(8):2218-2222.
63. Resnicoff M, Tjuvajev J, Rotman HL, et al. Regression of C6 rat brain tumors by cells expressing an antisense insulin-like growth factor I receptor RNA. J Exp Ther Oncol. 1996;1(6):385-389.
64. Kondziolka D, Lunsford LD, Claassen D, Pandalai S, Maitz AH, Flickinger JC. Radiobiology of radiosurgery: Part II. The rat C6 glioma model. Neurosurgery. 1992;31(2):280-287; discussion 287-288.
65. Beutler AS, Banck MS, Wedekind D, Hedrich HJ. Tumor gene therapy made easy: Allogeneic major histocompatibility complex in the C6 rat glioma model. Hum Gene Ther. 1999;10(1):95-101.
66. He J, Yin Y, Luster TA,Watkins L, Thorpe PE. Antiphosphatidylserine antibody combined with irradiation damages tumor blood vessels and induces tumor immunity in a rat model of glioblastoma. Clin Cancer Res. 2009;15(22):6871- 6880.
67. Mariani CL, Kouri JG, Streit WJ. Rejection of RG-2 gliomas is mediated by microglia and T lymphocytes. J Neurooncol. 2006;79(3):243-253.
68. Gunnersen JM, Spirkoska V, Smith PE, Danks RA, Tan SS. Growth and migration markers of rat C6 glioma cells identified by serial analysis of gene expression. Glia. 2000;32(2):146-154.
69. Schlegel J, Piontek G, Kersting M, et al. The p16/Cdkn2a/Ink4a gene is frequently deleted in nitrosourea-induced rat glial tumors. Pathobiology. 1999;67(4):202-206.
70. Westphal M, Meissner H. Establishing human glioma-derived cell lines. Methods Cell Biol. 1998;57:147-165.
71. Bigner SH, Schold SC, Friedman HS, Mark J, Bigner DD. Chromosomal composition of malignant human gliomas through serial subcutaneous transplantation in athymic mice. Cancer Genet Cytogenet. 1989;40(1):111-120.
72. Clark MJ, Homer N, O'Connor BD, et al. U87MG decoded: The genomic sequence of a cytogenetically aberrant human cancer cell line. PLoS Genet. 2010;6(1):e1000832.
73. McKeever PE, Davenport RD, Shakui P. Patterns of antigenic expression of human glioma cells. Crit Rev Neurobiol. 1991;6(2):119-147.
74. PaulusW, Huettner C, Tonn JC. Collagens, integrins and the mesenchymal drift in glioblastomas: A comparison of biopsy specimens, spheroid and early monolayer cultures. Int J Cancer. 1994;58(6):841-846.
75. Arnaout MA, Michishita M, Sharma CP. On the regulation of beta 2 integrins. Adv Exp Med Biol. 1992;323:171-179.
76. Anderson RC, Elder JB, Brown MD, et al. Changes in the immunologic phenotype of human malignant glioma cells after passaging in vitro. Clin Immunol. 2002;102(1):84-95.
77. Hansemann D. Ueber asymmetrische Zelltheilung in Epithelkrebsen und deren biologische Bedeutung. Virchows Arch Pathol Anat. 1890;119:299-326.
78. Boveri T. Zur Frage der Enstehung maligner Tumoren. Jena: Gustav Fischer Verlag, 1914.
79. Reynolds BA, Tetzlaff W, Weiss S. A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci. 1992;12(11):4565-4574.
80. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992;255(5052):1707-1710.
81. Vescovi AL, Reynolds BA, Fraser DD, Weiss S. bFGF regulates the proliferative fate of unipotent (neuronal) and bipotent (neuronal/astroglial) EGF-generated CNS progenitor cells. Neuron. 1993;11(5):951-966.
82. Galli R, Binda E, Orfanelli U, et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 2004;64(19):7011-7021.
83. Hemmati HD, Nakano I, Lazareff JA, et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA. 2003;100(25):15178-15183.
84. Ignatova TN, Kukekov VG, Laywell ED, Suslov ON, Vrionis FD, Steindler DA. Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia. 2002;39(3):193-206.
85. Tunici P, Bissola L, Lualdi E, et al. Genetic alterations and in vivo tumorigenicity of neurospheres derived from an adult glioblastoma. Mol Cancer. 2004;3:25.
86. Kelly JJ, Blough MD, Stechishin OD, et al. Oligodendroglioma cell lines containing t(1;19)(q10;p10). Neuro Oncol. 2010;12:745-755.
87. Chen R, Nishimura MC, Bumbaca SM, et al. A hierarchy of selfrenewing tumor-initiating cell types in glioblastoma. Cancer Cell. 2010;17(4):362-375.
88. Gunther HS, Schmidt NO, Phillips HS, et al. Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria. Oncogene. 2008;27(20):2897-2909.
89. Schulte A, Gunther HS, Phillips HS, et al. A distinct subset of glioma cell lines with stem cell-like properties reflects the transcriptional phenotype of glioblastomas and overexpresses CXCR4 as therapeutic target. Glia. 2011;59(4):590-602.
90. Wakimoto H, Mohapatra G, Kanai R, et al. Maintenance of primary tumor phenotype and genotype in glioblastoma stem cells. Neuro Oncol. 2011;14:132-144.
91. Bjerkvig R, Johansson M, Miletic H, Niclou SP. Cancer stem cells and angiogenesis. Semin Cancer Biol. 2009;19(5):279-284.
92. Wan F, Zhang S, Xie R, et al. The utility and limitations of neurosphere assay, CD133 immunophenotyping and side population assay in glioma stem cell research. Brain Pathol. 2010;20(5):877-889.
93. Pollard SM, Yoshikawa K, Clarke ID, et al. Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell. 2009;4(6):568-580.
94. Persson AI, Petritsch C, Swartling FJ, et al. Non-stem cell origin for oligodendroglioma. Cancer Cell. 2010;18(6):669-682.
95. Reynolds BA, Vescovi AL. Brain cancer stem cells: Think twice before going flat. Cell Stem Cell. 2009;5(5):466-467; author reply 468-469.
96. Grippo MC, Penteado PF, Carelli EF, Cruz-Hofling MA, Verinaud L. Establishment and partial characterization of a continuous human malignant glioma cell line: NG97. Cell Mol Neurobiol. 2001;21(4): 421-428.
97. Kruse CA, Varella-Garcia M, Kleinschmidt-Demasters BK, et al. Receptor expression, cytogenetic, and molecular analysis of six continuous human glioma cell lines. In Vitro Cell Dev Biol Anim. 1998;34(6):455-462.
98. Kelly JJ, Blough MD, Stechishin OD, et al. Oligodendroglioma cell lines containing t(1;19)(q10;p10). Neuro Oncol. 2010;12:745-755.
99. Luchman HA, Stechishin OD, Dang NH, et al. An in vivo patient-derived model of endogenous IDH1-mutant glioma. Neuro Oncol. 2012;14(2):184-191.
100. Bjerkvig R, Tonnesen A, Laerum OD, Backlund EO. Multicellular tumor spheroids from human gliomas maintained in organ culture. J Neurosurg. 1990;72(3):463-475.
101. Nygaard SJ, Haugland HK, Laerum OD, Lund-Johansen M, Bjerkvig R, Tysnes OB. Dynamic determination of human glioma invasion in vitro. J Neurosurg. 1998;89(3):441-447.
102. Wang J, Miletic H, Sakariassen PO, et al. A reproducible brain tumour model established from human glioblastoma biopsies. BMC Cancer. 2009;9:465.
103. Backlund EO, Bjerkvig R. Stereotactic biopsies as a model for studying the interaction between gliomas and normal brain tissue in vitro. J Neurosurg Sci. 1989;33(1):31-33.
104. Sakariassen PO, Prestegarden L, Wang J, et al. Angiogenesis-independent tumor growth mediated by stem-like cancer cells. Proc Natl Acad Sci USA. 2006;103(44):16466-16471.
105. Claes A, Schuuring J, Boots-Sprenger S, et al. Phenotypic and genotypic characterization of orthotopic human glioma models and its relevance for the study of anti-glioma therapy. Brain Pathol. 2008;18(3):423-433.
106. Taillandier L, Antunes L, Angioi-Duprez KS. Models for neurooncological preclinical studies: solid orthotopic and heterotopic grafts of human gliomas into nude mice. J Neurosci Methods. 2003;125(1- 2):147-157.
107. Giannini C, Sarkaria JN, Saito A, et al. Patient tumor EGFR and PDGFRA gene amplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme. Neuro Oncol. 2005;7(2):164-176.
108. Rolstad B. The athymic nude rat: An animal experimental model to reveal novel aspects of innate immune responses? Immunol Rev. 2001;184:136-144.
109. Keunen O, Johansson M, Oudin A, et al. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc Natl Acad Sci USA. 2011;108(9):3749-3754.
110. Huszthy PC, Giroglou T, Tsinkalovsky O, et al. Remission of invasive, cancer stem-like glioblastoma xenografts using lentiviral vectormediated suicide gene therapy. PLoS One. 2009;4(7):e6314.
111. Hodgson JG, Yeh RF, Ray A, et al. Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts. Neuro Oncol. 2009;11(5):477-487.
112. Huse JT, Holland EC. Targeting brain cancer: Advances in the molecular pathology of malignant glioma and medulloblastoma. Nat Rev Cancer. 2010;10(5):319-331.
113. Momota H, Holland EC. Mouse models of CNS embryonal tumors. Brain Tumor Pathol. 2009;26(2):43-50.
114. Fomchenko EI, Holland EC. Mouse models of brain tumors and their applications in preclinical trials. Clin Cancer Res. 2006;12(18): 5288-5297.
115. Wee B, Charles N, Holland EC. Animal models to study cancer-initiating cells from glioblastoma. Front Biosci. 2011;17:2243-2258.
116. Macleod KF, Jacks T. Insights into cancer from transgenic mouse models. J Pathol. 1999;187(1):43-60.
117. Talmadge JE, Hood KC, Zobel LC, Shafer LR, Coles M, Toth B. Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid suppressor cell expansion. Int Immunopharmacol. 2007;7(2):140-151.
118. Talmadge JE, Singh RK, Fidler IJ, Raz A. Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol. 2007;170(3):793-804.
119. Federspiel MJ, Bates P, Young JA, Varmus HE, Hughes SH. A system for tissue-specific gene targeting: Transgenic mice susceptible to subgroup A avian leukosis virus-based retroviral vectors. Proc Natl Acad Sci USA. 1994;91(23):11241-11245.
120. Greenhouse JJ, Petropoulos CJ, Crittenden LB, Hughes SH. Helper-independent retrovirus vectors with Rous-associated virus type O long terminal repeats. J Virol. 1988;62(12):4809-4812.
121. Guha A. Ras activation in astrocytomas and neurofibromas. Can J Neurol Sci. 1998;25(4):267-281.
122. 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): 150-153.
123. Henson JW, Schnitker BL, Correa KM, et al. The retinoblastoma gene is involved in malignant progression of astrocytomas. Ann Neurol. 1994;36(5):714-721.
124. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765-773.
125. Dai C, Celestino JC,Okada Y, Louis DN, Fuller GN, Holland EC. PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev. 2001;15(15): 1913-1925.
126. Charles NA, Holland EC, Gilbertson R, Glass R, Kettenmann H. The brain tumor microenvironment. Glia. 2012;60(3): 502-514.
127. DeNardo DG, Barreto JB, Andreu P, et al. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16(2): 91-102.
128. Charles N, Holland EC. The perivascular niche microenvironment in brain tumor progression. Cell Cycle. 2010;9(15): 3012-3021.
129. Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA. Effects of an Rb mutation in the mouse. Nature. 1992;359(6393): 295-300.
130. Weiss WA, Burns MJ, Hackett C, et al. Genetic determinants of malignancy in a mouse model for oligodendroglioma. Cancer Res. 2003;63(7):1589-1595.
131. Niclou SP, Danzeisen C, Eikesdal HP, et al. A novel eGFP-expressing immunodeficient mouse model to study tumor-host interactions. FASEB J. 2008;22(9):3120-3128.
132. Golebiewska A, Brons NH, Bjerkvig R, Niclou SP. Critical appraisal of the side population assay in stem cell and cancer stem cell research. Cell Stem Cell. 2011;8(2):136-147.
133. Gupta PB, Fillmore CM, Jiang G, et al. Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell. 2011;146(4):633-644.