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Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas

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Abstract

In this review we will describe eight commonly used rat brain tumor models and their application for the development of novel therapeutic and diagnostic modalities. The C6, 9L and T9 gliomas were induced by repeated injections of methylnitrosourea (MNU) to adult rats. The C6 glioma has been used extensively for a variety of studies, but since it arose in an outbred Wistar rat, it is not syngeneic to any inbred strain, and its potential to evoke an alloimmune response is a serious limitation. The 9L gliosarcoma has been used widely and has provided important information relating to brain tumor biology and therapy. The T9 glioma, although not generally recognized, was and probably still is the same as the 9L. Both of these tumors arose in Fischer rats and can be immunogenic in syngeneic hosts, a fact that must be taken into consideration when used in therapy studies, especially if survival is the endpoint. The RG2 and F98 gliomas were both chemically induced by administering ethylnitrosourea (ENU) to pregnant rats, the progeny of which developed brain tumors that subsequently were propagated in vitro and cloned. They are either weakly or non-immunogenic and have an invasive pattern of growth and uniform lethality, which make them particularly attractive models to test new therapeutic modalities. The CNS-1 glioma was induced by administering MNU to a Lewis rat. It has an infiltrative pattern of growth and is weakly immunogenic, which should make it useful in experimental neuro-oncology. Finally, the BT4C glioma was induced by administering ENU to a BD IX rat, following which brain cells were propagated in vitro until a tumorigenic clone was isolated. This tumor has been used for a variety of studies to evaluate new therapeutic modalities. The Avian Sarcoma Virus (ASV) induced tumors, and a continuous cell line derived from one of them designated RT-2, have been useful for studies in which de novo tumor induction is an important requirement. These tumors also are immunogenic and this limits their usefulness for therapy studies. It is essential to recognize the limitations of each of the models that have been described, and depending upon the nature of the study to be conducted, it is important that the appropriate model be selected.

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References

  1. Fomchenko EI, Holland EC (2006) Mouse models of brain tumors and their applications in preclinical trials. Clin Cancer Res 12:5288–5297. doi:10.1158/1078-0432.CCR-06-0438

    Article  PubMed  CAS  Google Scholar 

  2. Lampson LA (2001) New animal models to probe brain tumor biology, therapy, and immunotherapy: advantages and remaining concerns. J Neurooncol 53:275–287. doi:10.1023/A:1012230113527

    Article  PubMed  CAS  Google Scholar 

  3. Kimmelman J, Nalbantoglu J (2007) Faithful companions: a proposal for neurooncology trials in pet dogs. Cancer Res 67:4541–4544. doi:10.1158/0008-5472.CAN-06-3792

    Article  PubMed  CAS  Google Scholar 

  4. Krushelnycky BW, Farr-Jones MA, Mielke B et al (1991) Development of a large-animal human brain tumor xenograft model in immunosuppressed cats. Cancer Res 51:2430–2437

    PubMed  CAS  Google Scholar 

  5. Barth RF (1998) Rat brain tumor models in experimental neuro-oncology: the 9L, C6, T9, F98, RG2 (D74), RT-2 and CNS-1 gliomas. J Neurooncol 36:91–102. doi:10.1023/A:1005805203044

    Article  PubMed  CAS  Google Scholar 

  6. Candolfi M, Curtin JF, Nichols WS et al (2007) Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression. J Neurooncol 85:133–148. doi:10.1007/s11060-007-9400-9

    Article  PubMed  Google Scholar 

  7. Reilly KM, Rubin JB, Gilbertson RJ et al (2008) Rethinking brain tumors: the fourth mouse models of human cancers consortium nervous system tumors workshop. Cancer Res 68:5508–5511. doi:10.1158/0008-5472.CAN-08-0703

    Article  PubMed  CAS  Google Scholar 

  8. Barker M, Hoshino T, Gurcay O et al (1973) Development of an animal brain tumor model and its response to therapy with 1, 3-bis(2-chloroethyl)-1-nitrosourea. Cancer Res 33:976–986

    PubMed  CAS  Google Scholar 

  9. Kobayashi N, Allen N, Clendenon NR et al (1980) An improved rat brain-tumor model. J Neurosurg 53:808–815

    Article  PubMed  CAS  Google Scholar 

  10. Landen JW, Hau V, Wang M et al (2004) Noscapine crosses the blood-brain barrier and inhibits glioblastoma growth. Clin Cancer Res 10:5187–5201. doi:10.1158/1078-0432.CCR-04-0360

    Article  PubMed  CAS  Google Scholar 

  11. Lal S, Lacroix M, Tofilon P et al (2000) An implantable guide-screw system for brain tumor studies in small animals. J Neurosurg 92:326–333

    Article  PubMed  CAS  Google Scholar 

  12. Saini M, Roser F, Samii M et al (2004) A model for intratumoural chemotherapy in the rat brain. Acta Neurochir (Wien) 146:731–734. doi:10.1007/s00701-004-0261-0

    Article  CAS  Google Scholar 

  13. Benda P, Lightbody J, Sato G et al (1968) Differentiated rat glial cell strain in tissue culture. Science 161:370–371. doi:10.1126/science.161.3839.370

    Article  PubMed  CAS  Google Scholar 

  14. Schmidek HH, Nielsen SL, Schiller AL et al (1971) Morphological studies of rat brain tumors induced by N-nitrosomethylurea. J Neurosurg 34:335–340

    Article  PubMed  CAS  Google Scholar 

  15. Pfeiffer SE, Herschman HR, Lightbody J et al (1970) Synthesis by a clonal line of rat glial cells of a protein unique to the nervous system. J Cell Physiol 75:329–339. doi:10.1002/jcp.1040750309

    Article  PubMed  CAS  Google Scholar 

  16. Schlegel J, Piontek G, Kersting M et al (1999) The p16/Cdkn2a/Ink4a gene is frequently deleted in nitrosourea-induced rat glial tumors. Pathobiology 67:202–206. doi:10.1159/000028073

    Article  PubMed  CAS  Google Scholar 

  17. Asai A, Miyagi Y, Sugiyama A et al (1994) Negative effects of wild-type p53 and s-myc on cellular growth and tumorigenicity of glioma cells. Implication of the tumor suppressor genes for gene therapy. J Neurooncol 19:259–268. doi:10.1007/BF01053280

    Article  PubMed  CAS  Google Scholar 

  18. Sibenaller ZA, Etame AB, Ali MM et al (2005) Genetic characterization of commonly used glioma cell lines in the rat animal model system. Neurosurg Focus 19:E1. doi:10.3171/foc.2005.19.4.2

    Article  PubMed  Google Scholar 

  19. Guo P, Hu B, Gu W et al (2003) Platelet-derived growth factor-B enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment. Am J Pathol 162:1083–1093

    PubMed  CAS  Google Scholar 

  20. Heimberger AB, Suki D, Yang D et al (2005) The natural history of EGFR and EGFRvIII in glioblastoma patients. J Transl Med 3:38. doi:10.1186/1479-5876-3-38

    Article  PubMed  CAS  Google Scholar 

  21. Morford LA, Boghaert ER, Brooks WH et al (1997) Insulin-like growth factors (IGF) enhance three-dimensional (3D) growth of human glioblastomas. Cancer Lett 115:81–90. doi:10.1016/S0304-3835(97)04717-4

    Article  PubMed  CAS  Google Scholar 

  22. Assanah M, Lochhead R, Ogden A et al (2006) Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retroviruses. J Neurosci 26:6781–6790. doi:10.1523/JNEUROSCI.0514-06.2006

    Article  PubMed  CAS  Google Scholar 

  23. Nakada M, Niska JA, Tran NL et al (2005) EphB2/R-ras signaling regulates glioma cell adhesion, growth, and invasion. Am J Pathol 167:565–576

    PubMed  CAS  Google Scholar 

  24. Lampson LA, Lampson MA, Dunne AD (1993) Exploiting the lacZ reporter gene for quantitative analysis of disseminated tumor growth within the brain: use of the lacZ gene product as a tumor antigen, for evaluation of antigenic modulation, and to facilitate image analysis of tumor growth in situ. Cancer Res 53:176–182

    PubMed  CAS  Google Scholar 

  25. Doblas S, Saunders D, Kshirsagar P et al (2008) Phenyl-tert-butylnitrone induces tumor regression and decreases angiogenesis in a C6 rat glioma model. Free Radic Biol Med 44:63–72. doi:10.1016/j.freeradbiomed.2007.09.006

    Article  PubMed  CAS  Google Scholar 

  26. Solly F, Fish R, Simard B et al (2008) Tissue-type plasminogen activator has antiangiogenic properties without effect on tumor growth in a rat C6 glioma model. Cancer Gene Ther 15:685–692. doi:10.1038/cgt.2008.36

    Article  PubMed  CAS  Google Scholar 

  27. Ahmed AE, Jacob S, Nagy AA et al (2008) Dibromoacetonitrile-induced protein oxidation and inhibition of proteasomal activity in rat glioma cells. Toxicol Lett 179:29–33. doi:10.1016/j.toxlet.2008.03.017

    Article  PubMed  CAS  Google Scholar 

  28. Zhao S, Zhang X, Zhang J et al (2008) Intravenous administration of arsenic trioxide encapsulated in liposomes inhibits the growth of C6 gliomas in rat brains. J Chemother 20:253–262

    PubMed  CAS  Google Scholar 

  29. Sheehan J, Ionescu A, Pouratian N et al (2008) Use of trans sodium crocetinate for sensitizing glioblastoma multiforme to radiation: laboratory investigation. J Neurosurg 108:972–978. doi:10.3171/JNS/2008/108/5/0972

    Article  PubMed  Google Scholar 

  30. Mannino S, Molinari A, Sabatino G et al (2008) Intratumoral vs systemic administration of meta-tetrahydroxyphenylchlorin for photodynamic therapy of malignant gliomas: assessment of uptake and spatial distribution in C6 rat glioma model. Int J Immunopathol Pharmacol 21:227–231

    PubMed  CAS  Google Scholar 

  31. Yang WQ, Lun X, Palmer CA et al (2004) Efficacy and safety evaluation of human reovirus type 3 in immunocompetent animals: racine and nonhuman primates. Clin Cancer Res 10:8561–8576. doi:10.1158/1078-0432.CCR-04-0940

    Article  PubMed  Google Scholar 

  32. Tanriover N, Ulu MO, Sanus GZ et al (2008) The effects of systemic and intratumoral interleukin-12 treatment in C6 rat glioma model. Neurol Res 30:511–517. doi:10.1179/174313208X289516

    Article  PubMed  CAS  Google Scholar 

  33. Parsa AT, Chakrabarti I, Hurley PT et al (2000) Limitations of the C6/Wistar rat intracerebral glioma model: implications for evaluating immunotherapy. Neurosurgery 47:993–999. doi:10.1097/00006123-200010000-00050 discussion 999–1000

    Article  PubMed  CAS  Google Scholar 

  34. Trojan J, Johnson TR, Rudin SD et al (1993) Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNA. Science 259:94–97. doi:10.1126/science.8418502

    Article  PubMed  CAS  Google Scholar 

  35. Johnson TR, Trojan J, Rudin SD, Ilan J, Tykocinski ML (1993) Evoking an immune response to glioblastoma cells transfected with episome-based plasmid expressing insulin-like growth factor I. In: Levine AJ, Schmidek HH (eds) Molecular genetics of nervous system tumors. Wiley-Liss Inc., New York, pp 387–400

    Google Scholar 

  36. Karmakar S, Olive MF, Banik NL et al (2007) Intracranial stereotaxic cannulation for development of orthotopic glioblastoma allograft in Sprague-Dawley rats and histoimmunopathological characterization of the brain tumor. Neurochem Res 32:2235–2242. doi:10.1007/s11064-007-9450-6

    Article  PubMed  CAS  Google Scholar 

  37. Assadian S, Aliaga A, Del Maestro RF et al (2008) FDG-PET imaging for the evaluation of antiglioma agents in a rat model. Neuro-oncol 10:292–299. doi:10.1215/15228517-2008-014

    Article  PubMed  Google Scholar 

  38. Valable S, Lemasson B, Farion R et al (2008) Assessment of blood volume, vessel size, and the expression of angiogenic factors in two rat glioma models: a longitudinal in vivo and ex vivo study. NMR Biomed 21:1043–1056. doi:10.1002/nbm.1278

    Article  PubMed  CAS  Google Scholar 

  39. Valable S, Barbier EL, Bernaudin M et al (2008) In vivo MRI tracking of exogenous monocytes/macrophages targeting brain tumors in a rat model of glioma. Neuroimage 40:973–983. doi:10.1016/j.neuroimage.2008.01.005

    Article  PubMed  Google Scholar 

  40. Shen G, Shen F, Shi Z et al (2008) Identification of cancer stem-like cells in the C6 glioma cell line and the limitation of current identification methods. In Vitro Cell Dev Biol Anim 44:280–289. doi:10.1007/s11626-008-9115-z

    Article  PubMed  CAS  Google Scholar 

  41. Benda P, Someda K, Messer J et al (1971) Morphological and immunochemical studies of rat glial tumors and clonal strains propagated in culture. J Neurosurg 34:310–323

    Article  PubMed  CAS  Google Scholar 

  42. Ghods AJ, Irvin D, Liu G et al (2007) Spheres isolated from 9L gliosarcoma rat cell line possess chemoresistant and aggressive cancer stem-like cells. Stem Cells 25:1645–1653. doi:10.1634/stemcells.2006-0624

    Article  PubMed  CAS  Google Scholar 

  43. Barcellos-Hoff MH, Linfoot PA, Marton LJ et al (1992) Production of stable phenotypes from 9L rat brain tumor multicellular spheroids treated with 1, 3-bis(2-chloroethyl)-1-nitrosourea. Int J Cancer 52:409–413. doi:10.1002/ijc.2910520314

    Article  PubMed  CAS  Google Scholar 

  44. Schepkin VD, Lee KC, Kuszpit K et al (2006) Proton and sodium MRI assessment of emerging tumor chemotherapeutic resistance. NMR Biomed 19:1035–1042. doi:10.1002/nbm.1074

    Article  PubMed  CAS  Google Scholar 

  45. Black KL, Yin D, Konda BM et al (2008) Different effects of KCa and KATP agonists on brain tumor permeability between syngeneic and allogeneic rat models. Brain Res 1227:198–206. doi:10.1016/j.brainres.2008.06.046

    Article  PubMed  CAS  Google Scholar 

  46. Fross RD, Warnke PC, Groothuis DR (1991) Blood flow and blood-to-tissue transport in 9L gliosarcomas: the role of the brain tumor model in drug delivery research. J Neurooncol 11:185–197. doi:10.1007/BF00165526

    Article  PubMed  CAS  Google Scholar 

  47. Khan A, Jallo GI, Liu YJ et al (2005) Infusion rates and drug distribution in brain tumor models in rats. J Neurosurg 102:53–58

    PubMed  Google Scholar 

  48. Warnke PC, Blasberg RG, Groothuis DR (1987) The effect of hyperosmotic blood-brain barrier disruption on blood-to-tissue transport in ENU-induced gliomas. Ann Neurol 22:300–305. doi:10.1002/ana.410220304

    Article  PubMed  CAS  Google Scholar 

  49. Bansal A, Shuyan W, Hara T et al (2008) Biodisposition and metabolism of [(18)F]fluorocholine in 9L glioma cells and 9L glioma-bearing Fisher rats. Eur J Nucl Med Mol Imaging 35:1192–1203. doi:10.1007/s00259-008-0736-y

    Article  PubMed  CAS  Google Scholar 

  50. Yuan H, Schroeder T, Bowsher JE et al (2006) Intertumoral differences in hypoxia selectivity of the PET imaging agent 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone). J Nucl Med 47:989–998

    PubMed  CAS  Google Scholar 

  51. Wolff JE, Molenkamp G, Hotfilder M et al (1997) Dexamethasone inhibits glioma-induced formation of capillary like structures in vitro and angiogenesis in vivo. Klin Padiatr 209:275–277. doi:10.1055/s-2008-1043962

    Article  PubMed  CAS  Google Scholar 

  52. Yang H, Chopp M, Zhang X et al (2007) Using behavioral measurement to assess tumor progression and functional outcome after antiangiogenic treatment in mouse glioma models. Behav Brain Res 182:42–50. doi:10.1016/j.bbr.2007.05.013

    Article  PubMed  CAS  Google Scholar 

  53. Regnard P, Le Duc G, Brauer-Krisch E et al (2008) Irradiation of intracerebral 9L gliosarcoma by a single array of microplanar x-ray beams from a synchrotron: balance between curing and sparing. Phys Med Biol 53:861–878. doi:10.1088/0031-9155/53/4/003

    Article  PubMed  Google Scholar 

  54. Bencokova Z, Pauron L, Devic C et al (2008) Molecular and cellular response of the most extensively used rodent glioma models to radiation and/or cisplatin. J Neurooncol 86:13–21. doi:10.1007/s11060-007-9433-0

    Article  PubMed  CAS  Google Scholar 

  55. Donawho CK, Luo Y, Luo Y et al (2007) ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res 13:2728–2737. doi:10.1158/1078-0432.CCR-06-3039

    Article  PubMed  CAS  Google Scholar 

  56. Barba D, Hardin J, Ray J et al (1993) Thymidine kinase-mediated killing of rat brain tumors. J Neurosurg 79:729–735

    Article  PubMed  CAS  Google Scholar 

  57. Iwadate Y, Inoue M, Saegusa T et al (2005) Recombinant Sendai virus vector induces complete remission of established brain tumors through efficient interleukin-2 gene transfer in vaccinated rats. Clin Cancer Res 11:3821–3827. doi:10.1158/1078-0432.CCR-04-1485

    Article  PubMed  CAS  Google Scholar 

  58. Kumar S, Brown SL, Kolozsvary A et al (2008) Efficacy of suicide gene therapy in hypoxic rat 9L glioma cells. J Neurooncol 90:19–24. doi:10.1007/s11060-008-9635-0

    Article  PubMed  CAS  Google Scholar 

  59. Miletic H, Fischer Y, Litwak S et al (2007) Bystander killing of malignant glioma by bone marrow-derived tumor-infiltrating progenitor cells expressing a suicide gene. Mol Ther 15:1373–1381. doi:10.1038/sj.mt.6300155

    Article  PubMed  CAS  Google Scholar 

  60. Chignola R, Foroni R, Franceschi A et al (1995) Heterogeneous response of individual multicellular tumour spheroids to immunotoxins and ricin toxin. Br J Cancer 72:607–614

    PubMed  CAS  Google Scholar 

  61. Liu Y, Wang Q, Kleinschmidt-DeMasters BK et al (2007) TGF-beta2 inhibition augments the effect of tumor vaccine and improves the survival of animals with pre-established brain tumors. J Neurooncol 81:149–162. doi:10.1007/s11060-006-9222-1

    Article  PubMed  CAS  Google Scholar 

  62. Aghi M, Chou TC, Suling K et al (1999) Multimodal cancer treatment mediated by a replicating oncolytic virus that delivers the oxazaphosphorine/rat cytochrome P450 2B1 and ganciclovir/herpes simplex virus thymidine kinase gene therapies. Cancer Res 59:3861–3865

    PubMed  CAS  Google Scholar 

  63. Madara J, Krewet JA, Shah M (2005) Heat shock protein 72 expression allows permissive replication of oncolytic adenovirus dl1520 (ONYX-015) in rat glioblastoma cells. Mol Cancer 4:12. doi:10.1186/1476-4598-4-12

    Article  PubMed  CAS  Google Scholar 

  64. Blume MR, Wilson CP, Vasquez DA (1974) Immune response to a transplantable intracerebral glioma in rats. In: Sane K, Ishi S, Le Vey D (eds) Recent progress in neurological surgery. Excerpta Medica, Amsterdam, pp 129–134

    Google Scholar 

  65. Denlinger RH, Axler DA, Koestner A et al (1975) Tumor-specific transplantation immunity to intracerebral challenge with cells from a methylnitrosourea-induced brain tumor. J Med 6:249–259

    PubMed  CAS  Google Scholar 

  66. Morantz RA, Wood GW, Foster M et al (1979) Macrophages in experimental and human brain tumors. Part 1: Studies of the macrophage content of experimental rat brain tumors of varying immunogenicity. J Neurosurg 50:298–304

    Article  PubMed  CAS  Google Scholar 

  67. Chen CY, Chang YN, Ryan P et al (1995) Effect of herpes simplex virus thymidine kinase expression levels on ganciclovir-mediated cytotoxicity and the “bystander effect”. Hum Gene Ther 6:1467–1476. doi:10.1089/hum.1995.6.11-1467

    Article  PubMed  CAS  Google Scholar 

  68. Moolten FL (1986) Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res 46:5276–5281

    PubMed  CAS  Google Scholar 

  69. Coderre J, Rubin P, Freedman A et al (1994) Selective ablation of rat brain tumors by boron neutron capture therapy. Int J Radiat Oncol Biol Phys 28:1067–1077

    PubMed  CAS  Google Scholar 

  70. Moriuchi S, Wolfe D, Tamura M et al (2002) Double suicide gene therapy using a replication defective herpes simplex virus vector reveals reciprocal interference in a malignant glioma model. Gene Ther 9:584–591. doi:10.1038/sj.gt.3301693

    Article  PubMed  CAS  Google Scholar 

  71. Namba H, Tagawa M, Miyagawa T et al (2000) Treatment of rat experimental brain tumors by herpes simplex virus thymidine kinase gene-transduced allogeneic tumor cells and ganciclovir. Cancer Gene Ther 7:947–953. doi:10.1038/sj.cgt.7700172

    Article  PubMed  CAS  Google Scholar 

  72. Smilowitz HM, Micca PL, Nawrocky MM et al (2000) The combination of boron neutron-capture therapy and immunoprophylaxis for advanced intracerebral gliosarcomas in rats. J Neurooncol 46:231–240. doi:10.1023/A:1006409721365

    Article  PubMed  CAS  Google Scholar 

  73. Stojiljkovic M, Piperski V, Dacevic M et al (2003) Characterization of 9L glioma model of the Wistar rat. J Neurooncol 63:1–7. doi:10.1023/A:1023732619651

    Article  PubMed  Google Scholar 

  74. Bhattacharya P, Chekmenev EY, Perman WH et al (2007) Towards hyperpolarized (13)C-succinate imaging of brain cancer. J Magn Reson 186:150–155. doi:10.1016/j.jmr.2007.01.017

    Article  PubMed  CAS  Google Scholar 

  75. Jallo GI, Volkov A, Wong C et al (2006) A novel brainstem tumor model: functional and histopathological characterization. Childs Nerv Syst 22:1519–1525. doi:10.1007/s00381-006-0174-8

    Article  PubMed  Google Scholar 

  76. Saito R, Bringas J, Mirek H et al (2004) Invasive phenotype observed in 1, 3-bis(2-chloroethyl)-1-nitrosourea-resistant sublines of 9L rat glioma cells: a tumor model mimicking a recurrent malignant glioma. J Neurosurg 101:826–831

    Article  PubMed  Google Scholar 

  77. Schepkin VD, Lee KC, Kuszpit K et al (2006) Proton and sodium MRI assessment of emerging tumor chemotherapeutic resistance. NMR Biomed 19:1035–1042. doi:10.1002/nbm.1074

    Article  PubMed  CAS  Google Scholar 

  78. Kida Y, Cravioto H, Hochwald GM et al (1983) Immunity to transplantable nitrosourea-induced neurogenic tumors. II. Immunoprophylaxis of tumors of the brain. J Neuropathol Exp Neurol 42:122–135. doi:10.1097/00005072-198303000-00002

    Article  PubMed  CAS  Google Scholar 

  79. Jeffes EW, Zhang JG, Hoa N et al (2005) Antiangiogenic drugs synergize with a membrane macrophage colony-stimulating factor-based tumor vaccine to therapeutically treat rats with an established malignant intracranial glioma. J Immunol 174:2533–2543

    PubMed  CAS  Google Scholar 

  80. Pietronigro D, Drnovsky F, Cravioto H et al (2003) DTI-015 produces cures in T9 gliosarcoma. Neoplasia 5:17–22

    PubMed  CAS  Google Scholar 

  81. Shibuya N, Hochgeschwender U, Kida Y et al (1984) Immunity to transplantable nitrosourea-induced neurogenic tumors. III. Systemic adoptive transfer of immunity. J Neuropathol Exp Neurol 43:426–438. doi:10.1097/00005072-198407000-00007

    Article  PubMed  CAS  Google Scholar 

  82. Harada K, Yoshida J, Mizuno M et al (1995) Growth inhibition of intracerebral rat glioma by transfection-induced human interferon-beta. J Surg Oncol 59:105–109

    Article  PubMed  CAS  Google Scholar 

  83. Ko L, Koestner A, Wechsler W (1980) Morphological characterization of nitrosourea-induced glioma cell lines and clones. Acta Neuropathol 51:23–31. doi:10.1007/BF00688846

    Article  PubMed  CAS  Google Scholar 

  84. Weizsacker M, Nagamune A, Winkelstroter R et al (1982) Radiation and drug response of the rat glioma RG2. Eur J Cancer Clin Oncol 18:891–895. doi:10.1016/0277-5379(82)90200-0

    Article  PubMed  CAS  Google Scholar 

  85. Ferrier MC, Sarin H, Fung SH et al (2007) Validation of dynamic contrast-enhanced magnetic resonance imaging-derived vascular permeability measurements using quantitative autoradiography in the RG2 rat brain tumor model. Neoplasia 9:546–555. doi:10.1593/neo.07289

    Article  PubMed  CAS  Google Scholar 

  86. Ningaraj NS, Rao M, Hashizume K et al (2002) Regulation of blood-brain tumor barrier permeability by calcium-activated potassium channels. J Pharmacol Exp Ther 301:838–851. doi:10.1124/jpet.301.3.838

    Article  PubMed  CAS  Google Scholar 

  87. Hashizume K, Black KL (2002) Increased endothelial vesicular transport correlates with increased blood-tumor barrier permeability induced by bradykinin and leukotriene C4. J Neuropathol Exp Neurol 61:725–735

    PubMed  CAS  Google Scholar 

  88. Zagorac D, Jakovcevic D, Gebremedhin D et al (2008) Antiangiogenic effect of inhibitors of cytochrome P450 on rats with glioblastoma multiforme. J Cereb Blood Flow Metab 28:1431–1439. doi:10.1038/jcbfm.2008.31

    Article  PubMed  CAS  Google Scholar 

  89. Wang W, Tai CK, Kershaw AD et al (2006) Use of replication-competent retroviral vectors in an immunocompetent intracranial glioma model. Neurosurg Focus 20:E25. doi:10.3171/foc.2006.20.1.8

    Article  PubMed  Google Scholar 

  90. Miknyoczki S, Chang H, Grobelny J et al (2007) The selective poly(ADP-ribose) polymerase-1(2) inhibitor, CEP-8983, increases the sensitivity of chemoresistant tumor cells to temozolomide and irinotecan but does not potentiate myelotoxicity. Mol Cancer Ther 6:2290–2302. doi:10.1158/1535-7163.MCT-07-0062

    Article  PubMed  CAS  Google Scholar 

  91. Tsai NM, Lin SZ, Lee CC et al (2005) The antitumor effects of angelica sinensis on malignant brain tumors in vitro and in vivo. Clin Cancer Res 11:3475–3484. doi:10.1158/1078-0432.CCR-04-1827

    Article  PubMed  Google Scholar 

  92. Shen DH, Marsee DK, Schaap J et al (2004) Effects of dose, intervention time, and radionuclide on sodium iodide symporter (NIS)-targeted radionuclide therapy. Gene Ther 11:161–169. doi:10.1038/sj.gt.3302147

    Article  PubMed  CAS  Google Scholar 

  93. Oshiro S, Liu Y, Fukushima T et al (2001) Modified immunoregulation associated with interferon-gamma treatment of rat glioma. Neurol Res 23:359–366. doi:10.1179/016164101101198569

    Article  PubMed  CAS  Google Scholar 

  94. Kurozumi K, Hardcastle J, Thakur R et al (2007) Effect of tumor microenvironment modulation on the efficacy of oncolytic virus therapy. J Natl Cancer Inst 99:1768–1781. doi:10.1093/jnci/djm229

    Article  PubMed  CAS  Google Scholar 

  95. Wakimoto H, Fulci G, Tyminski E et al (2004) Altered expression of antiviral cytokine mRNAs associated with cyclophosphamide’s enhancement of viral oncolysis. Gene Ther 11:214–223. doi:10.1038/sj.gt.3302143

    Article  PubMed  CAS  Google Scholar 

  96. Mathieu D, Lecomte R, Tsanaclis AM et al (2007) Standardization and detailed characterization of the syngeneic Fischer/F98 glioma model. Can J Neurol Sci 34:296–306

    PubMed  Google Scholar 

  97. von Eckardstein KL, Patt S, Kratzel C et al (2005) Local chemotherapy of F98 rat glioblastoma with paclitaxel and carboplatin embedded in liquid crystalline cubic phases. J Neurooncol 72:209–215. doi:10.1007/s11060-004-3010-6

    Article  CAS  Google Scholar 

  98. Biston MC, Joubert A, Adam JF et al (2004) Cure of Fischer rats bearing radioresistant F98 glioma treated with cis-platinum and irradiated with monochromatic synchrotron X-rays. Cancer Res 64:2317–2323. doi:10.1158/0008-5472.CAN-03-3600

    Article  PubMed  CAS  Google Scholar 

  99. Rousseau J, Boudou C, Barth RF et al (2007) Enhanced survival and cure of F98 glioma-bearing rats following intracerebral delivery of carboplatin in combination with photon irradiation. Clin Cancer Res 13:5195–5201. doi:10.1158/1078-0432.CCR-07-1002

    Article  PubMed  CAS  Google Scholar 

  100. Rousseau R, Barth RF, Moeschberger ML et al. (2008) Efficacy of intracerebral delivery of carboplatin in combination with photon irradiation for treatment of F98 glioma bearing rats. Int J Radiat Oncol Biol Phys 73:530–536

    Google Scholar 

  101. Barth RF, Yang W, Coderre JA (2003) Rat brain tumor models to assess the efficacy of boron neutron capture therapy: a critical evaluation. J Neurooncol 62:61–74

    PubMed  Google Scholar 

  102. Yang W, Wu G, Barth RF et al (2008) Molecular targeting and treatment of composite EGFR and EGFRvIII-positive gliomas using boronated monoclonal antibodies. Clin Cancer Res 14:883–891. doi:10.1158/1078-0432.CCR-07-1968

    Article  PubMed  CAS  Google Scholar 

  103. Cho JY, Shen DH, Yang W et al (2002) In vivo imaging and radioiodine therapy following sodium iodide symporter gene transfer in animal model of intracerebral gliomas. Gene Ther 9:1139–1145. doi:10.1038/sj.gt.3301787

    Article  PubMed  CAS  Google Scholar 

  104. Adam JF, Joubert A, Biston MC et al (2006) Prolonged survival of Fischer rats bearing F98 glioma after iodine-enhanced synchrotron stereotactic radiotherapy. Int J Radiat Oncol Biol Phys 64:603–611. doi:10.1016/j.ijrobp.2005.09.004

    PubMed  CAS  Google Scholar 

  105. Blanchard J, Mathieu D, Patenaude Y et al (2006) MR-pathological comparison in F98-Fischer glioma model using a human gantry. Can J Neurol Sci 33:86–91

    PubMed  Google Scholar 

  106. Zhang J, van Zijl PC, Laterra J et al (2007) Unique patterns of diffusion directionality in rat brain tumors revealed by high-resolution diffusion tensor MRI. Magn Reson Med 58:454–462. doi:10.1002/mrm.21371

    Article  PubMed  Google Scholar 

  107. Zhang D, Feng XY, Henning TD et al. (2008) MR imaging of tumor angiogenesis using sterically stabilized gd-DTPA liposomes targeted to CD105. Eur J Radiol. doi:10.1016/j.ejrad.2008.04.022

  108. Wu X, Hu J, Zhou L et al (2008) In vivo tracking of superparamagnetic iron oxide nanoparticle-labeled mesenchymal stem cell tropism to malignant gliomas using magnetic resonance imaging. Laboratory investigation. J Neurosurg 108:320–329. doi:10.3171/JNS/2008/108/2/0320

    Article  PubMed  Google Scholar 

  109. Tzeng JJ, Barth RF, Orosz CG et al (1991) Phenotype and functional activity of tumor-infiltrating lymphocytes isolated from immunogenic and nonimmunogenic rat brain tumors. Cancer Res 51:2373–2378

    PubMed  CAS  Google Scholar 

  110. Paul DB, Barth RF, Yang W et al (2000) B7.1 expression by the weakly immunogenic F98 rat glioma does not enhance immunogenicity. Gene Ther 7:993–999. doi:10.1038/sj.gt.3301209

    Article  PubMed  CAS  Google Scholar 

  111. Clavreul A, Delhaye M, Jadaud E et al (2006) Effects of syngeneic cellular vaccinations alone or in combination with GM-CSF on the weakly immunogenic F98 glioma model. J Neurooncol 79:9–17. doi:10.1007/s11060-005-9115-8

    Article  PubMed  CAS  Google Scholar 

  112. Hanissian SH, Teng B, Akbar U et al (2005) Regulation of myeloid leukemia factor-1 interacting protein (MLF1IP) expression in glioblastoma. Brain Res 1047:56–64. doi:10.1016/j.brainres.2005.04.017

    Article  PubMed  CAS  Google Scholar 

  113. von Eckardstein KL, Patt S, Zhu J et al (2001) Short-term neuropathological aspects of in vivo suicide gene transfer to the F98 rat glioblastoma using liposomal and viral vectors. Histol Histopathol 16:735–744

    Google Scholar 

  114. Fenstermaker RA, Capala J, Barth RF et al (1995) The effect of epidermal growth factor receptor (EGFR) expression on in vivo growth of rat C6 glioma cells. Leukemia 9(Suppl 1):S106–S112

    PubMed  Google Scholar 

  115. Yang W, Barth RF, Wu G et al (2005) Development of a syngeneic rat brain tumor model expressing EGFRvIII and its use for molecular targeting studies with monoclonal antibody L8A4. Clin Cancer Res 11:341–350

    PubMed  CAS  Google Scholar 

  116. Wu G, Yang W, Barth RF et al (2007) Molecular targeting and treatment of an epidermal growth factor receptor-positive glioma using boronated cetuximab. Clin Cancer Res 13:1260–1268. doi:10.1158/1078-0432.CCR-06-2399

    Article  PubMed  CAS  Google Scholar 

  117. Wu G, Barth RF, Yang W et al (2006) Targeted delivery of methotrexate to epidermal growth factor receptor-positive brain tumors by means of cetuximab (IMC-C225) dendrimer bioconjugates. Mol Cancer Ther 5:52–59. doi:10.1158/1535-7163.MCT-05-0325

    Article  PubMed  CAS  Google Scholar 

  118. Bryant MJ, Chuah TL, Luff J et al (2008) A novel rat model for glioblastoma multiforme using a bioluminescent F98 cell line. J Clin Neurosci 15:545–551. doi:10.1016/j.jocn.2007.04.022

    Article  PubMed  CAS  Google Scholar 

  119. Ernestus RI, Wilmes LJ, Hoehn-Berlage M (1992) Identification of intracranial liqor metastases of experimental stereotactically implanted brain tumors by the tumor-selective MRI contrast agent MnTPPS. Clin Exp Metastasis 10:345–350. doi:10.1007/BF00058174

    Article  PubMed  CAS  Google Scholar 

  120. Kruse CA, Molleston MC, Parks EP et al (1994) A rat glioma model, CNS-1, with invasive characteristics similar to those of human gliomas: a comparison to 9L gliosarcoma. J Neurooncol 22:191–200. doi:10.1007/BF01052919

    Article  PubMed  CAS  Google Scholar 

  121. Kielian T, van Rooijen N, Hickey WF (2002) MCP-1 expression in CNS-1 astrocytoma cells: implications for macrophage infiltration into tumors in vivo. J Neurooncol 56:1–12. doi:10.1023/A:1014495613455

    Article  PubMed  Google Scholar 

  122. Platten M, Kretz A, Naumann U et al (2003) Monocyte chemoattractant protein-1 increases microglial infiltration and aggressiveness of gliomas. Ann Neurol 54:388–392. doi:10.1002/ana.10679

    Article  PubMed  CAS  Google Scholar 

  123. Owens GC, Orr EA, DeMasters BK et al (1998) Overexpression of a transmembrane isoform of neural cell adhesion molecule alters the invasiveness of rat CNS-1 glioma. Cancer Res 58:2020–2028

    PubMed  CAS  Google Scholar 

  124. Lapointe M, Lanthier J, Moumdjian R et al (2005) Expression and activity of l-isoaspartyl methyltransferase decrease in stage progression of human astrocytic tumors. Brain Res Mol Brain Res 135:93–103. doi:10.1016/j.molbrainres.2004.12.008

    Article  PubMed  CAS  Google Scholar 

  125. Matthews RT, Gary SC, Zerillo C et al (2000) Brain-enriched hyaluronan binding (BEHAB)/brevican cleavage in a glioma cell line is mediated by a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family member. J Biol Chem 275:22695–22703. doi:10.1074/jbc.M909764199

    Article  PubMed  CAS  Google Scholar 

  126. Nutt CL, Zerillo CA, Kelly GM et al (2001) Brain enriched hyaluronan binding (BEHAB)/brevican increases aggressiveness of CNS-1 gliomas in lewis rats. Cancer Res 61:7056–7059

    PubMed  CAS  Google Scholar 

  127. Biglari A, Bataille D, Naumann U et al (2004) Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model. Cancer Gene Ther 11:721–732. doi:10.1038/sj.cgt.7700783

    Article  PubMed  CAS  Google Scholar 

  128. Ali S, Curtin JF, Zirger JM et al (2004) Inflammatory and anti-glioma effects of an adenovirus expressing human soluble Fms-like tyrosine kinase 3 ligand (hsFlt3L): treatment with hsFlt3L inhibits intracranial glioma progression. Mol Ther 10:1071–1084. doi:10.1016/j.ymthe.2004.08.025

    Article  PubMed  CAS  Google Scholar 

  129. Laerum OD, Rajewsky MF (1975) Neoplastic transformation of fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. J Natl Cancer Inst 55:1177–1187

    PubMed  CAS  Google Scholar 

  130. Laerum OD, Rajewsky MF, Schachner M et al (1977) Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 89:273–295. doi:10.1007/BF00283783

    Article  PubMed  CAS  Google Scholar 

  131. Stuhr LE, Raa A, Oyan AM et al (2007) Hyperoxia retards growth and induces apoptosis, changes in vascular density and gene expression in transplanted gliomas in nude rats. J Neurooncol 85:191–202. doi:10.1007/s11060-007-9407-2

    Article  PubMed  CAS  Google Scholar 

  132. Pulkkinen M, Pikkarainen J, Wirth T et al (2008) Three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology: formulation development and in vitro anticancer activity. Eur J Pharm Biopharm 70:66–74. doi:10.1016/j.ejpb.2008.04.018

    Article  PubMed  CAS  Google Scholar 

  133. Raty JK, Airenne KJ, Marttila AT et al (2004) Enhanced gene delivery by avidin-displaying baculovirus. Mol Ther 9:282–291. doi:10.1016/j.ymthe.2003.11.004

    Article  PubMed  CAS  Google Scholar 

  134. Huszthy PC, Brekken C, Pedersen TB et al (2006) Antitumor efficacy improved by local delivery of species-specific endostatin. J Neurosurg 104:118–128. doi:10.3171/jns.2006.104.1.118

    Article  PubMed  CAS  Google Scholar 

  135. Sandstrom M, Johansson M, Bergstrom P et al (2008) Effects of the VEGFR inhibitor ZD6474 in combination with radiotherapy and temozolomide in an orthotopic glioma model. J Neurooncol 88:1–9. doi:10.1007/s11060-008-9527-3

    Article  PubMed  CAS  Google Scholar 

  136. Vallbo C, Bergenheim T, Hedman H et al (2002) The antimicrotubule drug estramustine but not irradiation induces apoptosis in malignant glioma involving AKT and caspase pathways. J Neurooncol 56:143–148. doi:10.1023/A:1014562503097

    Article  PubMed  Google Scholar 

  137. Yoshida D, Noha M, Watanabe K et al (2001) The bleb formation of the extracellular pseudopodia; early evidence of microtubule depolymerization by estramustine phosphate in glioma cell; in vitro study. J Neurooncol 52:37–47. doi:10.1023/A:1010653613588

    Article  PubMed  CAS  Google Scholar 

  138. Andersson U, Grankvist K, Bergenheim AT et al (2002) Rapid induction of long-lasting drug efflux activity in brain vascular endothelial cells but not malignant glioma following irradiation. Med Oncol 19:1–9. doi:10.1385/MO:19:1:1

    Article  PubMed  CAS  Google Scholar 

  139. Griffin JL, Lehtimaki KK, Valonen PK et al (2003) Assignment of 1H nuclear magnetic resonance visible polyunsaturated fatty acids in BT4C gliomas undergoing ganciclovir-thymidine kinase gene therapy-induced programmed cell death. Cancer Res 63:3195–3201

    PubMed  CAS  Google Scholar 

  140. Garcia-Cabrera I, Edvardsen K, Tysnes BB et al (1996) The lac-z reporter gene: a tool for in vitro studies of malignant glioma cell invasion. Invasion Metastasis 16:107–115

    PubMed  CAS  Google Scholar 

  141. Pedersen PH, Edvardsen K, Garcia-Cabrera I et al (1995) Migratory patterns of lac-z transfected human glioma cells in the rat brain. Int J Cancer 62:767–771. doi:10.1002/ijc.2910620620

    Article  PubMed  CAS  Google Scholar 

  142. Copeland DD, Talley FA, Bigner DD (1976) The fine structure of intracranial neoplasms induced by the inoculation of avian sarcoma virus in neonatal and adult rats. Am J Pathol 83:149–176

    PubMed  CAS  Google Scholar 

  143. Prabhu SS, Broaddus WC, Oveissi C et al (2000) Determination of intracranial tumor volumes in a rodent brain using magnetic resonance imaging, Evans blue, and histology: a comparative study. IEEE Trans Biomed Eng 47:259–265. doi:10.1109/10.821776

    Article  PubMed  CAS  Google Scholar 

  144. Beckman WC Jr, Powers SK, Brown JT et al (1987) Differential retention of rhodamine 123 by avian sarcoma virus-induced glioma and normal brain tissue of the rat in vivo. Cancer 59:266–270. doi:10.1002/1097-0142(19870115)59:2<266::AID-CNCR2820590215>3.0.CO;2-6

    Article  PubMed  Google Scholar 

  145. Valerie K, Hawkins W, Farnsworth J et al (2001) Substantially improved in vivo radiosensitization of rat glioma with mutant HSV-TK and acyclovir. Cancer Gene Ther 8:3–8. doi:10.1038/sj.cgt.7700265

    Article  PubMed  CAS  Google Scholar 

  146. Valerie K, Brust D, Farnsworth J et al (2000) Improved radiosensitization of rat glioma cells with adenovirus-expressed mutant herpes simplex virus-thymidine kinase in combination with acyclovir. Cancer Gene Ther 7:879–884. doi:10.1038/sj.cgt.7700185

    Article  PubMed  CAS  Google Scholar 

  147. Shah MR, Ramsey WJ (2003) CD8 + T-cell mediated anti-tumor responses cross-reacting against 9L and RT2 rat glioma cell lines. Cell Immunol 225:113–121. doi:10.1016/j.cellimm.2003.10.004

    Article  PubMed  CAS  Google Scholar 

  148. Mourad PD, Farrell L, Stamps LD et al (2003) Quantitative assessment of glioblastoma invasion in vivo. Cancer Lett 192:97–107. doi:10.1016/S0304-3835(02)00637-7

    Article  PubMed  CAS  Google Scholar 

  149. Beutler AS, Banck MS, Wedekind D et al (1999) Tumor gene therapy made easy: allogeneic major histocompatibility complex in the C6 rat glioma model. Hum Gene Ther 10:95–101

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Pathology, The Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH, 43210, USA

    Rolf F. Barth

  2. Department of Neurological Surgery, Dardinger Laboratory for Neuro-Oncology and Neurosciences, The Ohio State University, 385-D OSUCCC, 410 West 12th Avenue, OSUCCC, Columbus, OH, 43210, USA

    Balveen Kaur

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Barth, R.F., Kaur, B. Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas. J Neurooncol 94, 299–312 (2009). https://doi.org/10.1007/s11060-009-9875-7

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