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Ganciclovir mediated regression of rat brain tumors expressing the herpes simplex virus thymidine kinase imaged by magnetic resonance.

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Maron, A Gustin, Thierry [MONT] Mottet, I. Demeure, R. Octave, Jean-Noël [UCL]

Using a rat C6 brain tumor model, we studied the antitumor effects of Herpes simplex virus type 1 thymidine kinase (HSV-tk) gene transfer followed by ganciclovir treatment. C6 glioma cells were transfected in vitro with the HSV-tk gene, and tested for their sensitivity to ganciclovir. Although there was no surviving cell at a 30 microM ganciclovir concentration, unmodified C6 cells were not affected by the drug. For in vivo experiments, intracerebral tumors were induced in rats by stereotactic injection of 10(4) HSV-tk-modified C6 cells. Ten days later, the animals were treated with intraperitoneal injections of ganciclovir for 21 days. The tumors evolution was evaluated by high resolution magnetic resonance imaging. In 33% of the rats, the signal intensity of the tumors became heterogeneous, with development of highly hyperintense areas, and a complete tumor regression was subsequently noted. Histological examination of successfully treated tumors revealed progressive necrosis with formation of cysts. The survival time of the HSV-tk/ganciclovir treated animals was consistently increased, all rats surviving more than 30 days and 33% of them being still alive after 80 days.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 1995
Journal information "Journal of neuro-oncology" - Vol. 24, no. 3, p. 259-65 (1995)
Peer reviewed yes
issn 0167-594X
Publication status Publié
Affiliations UCL - (MGD) Service de neurochirurgie
UCL - MD/CHIR - Département de chirurgie
MESH Subject Animals ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Brain Neoplasms - drug therapy - pathology ; Disease Models, Animal ; Ganciclovir - therapeutic use ; Gene Transfer Techniques ; Glioma - drug therapy - pathology ; Magnetic Resonance Imaging ; Male ; Neoplasm Staging ; Neoplasm Transplantation ; Rats ; Rats, Wistar ; Reproducibility of Results ; Simplexvirus - enzymology ; Survival Rate ; Thymidine Kinase - genetics - therapeutic use
Links
  1. Schoenberg BS: The epidemiology of nervous system tumors. In: Oncology of the Nervous System, MD Walker (eds). Martinus Nijhoff Publishers, Boston, 1983, pp 1?30
  2. Daumas-Duport C, Scheithauer B, O'Fallon J, Kelly P: Grading of astrocytomas: a simple and reproductible method. Cancer 62: 2152?2165, 1988
  3. Mahaley MS, Mettlin C, Natarajan N, Laws ER Jr, Peace BB: National survey of patterns of care for brain-tumor patients. J Neurosurg 71: 826?836, 1989
  4. Itaya T, Yamagiwa S, Okada F, Oikawa T, Kuzumaki N, Takeichi N, Hosokawa M, Kobayashi H: Xenogenization of a mouse lung carcinoma (3LL) by transfection with an allogenic class I major histocompatibility complex gene (H-2Ld). Cancer Res 47: 3136?3140, 1987
  5. Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B, Frost P: Interleu-kin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 60: 397?403, 1990
  6. Tepper RI, Pattengale PK, Leder P: Murine interleukin-4 potent anti-tumor activityin vivo. Cell 57: 503?512, 1989
  7. Wei MX, Hurford RK Jr, Tepper RI, Breakefield XO, Chiocca EA: Genetic treatment of intracerebral rodent brain tumors with an interleukin-4 retrovirus vector (Abstract). Soc Neurosci 19: 1071, 1993
  8. Gansbacher B, Bannerji R, Daniels B, Zier K, Cronin K, Gilboa E: Retroviral vector-mediated ?-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res 50: 7820?7825, 1990
  9. Ram Z, Walbridge S, Heiss JD, Culver KW, Blaese RM, Oldfield EH:In vivo transfer of the human interleukin-2 gene: negative tumoricidal results in experimental brain tumors. J Neurosurg 80: 535?54, 1994
  10. Austin EA, Huber BE: A first step in the development of gene therapy for colorectal carcinoma: cloning, sequencing, and expression of Escherichia coli cytosine deaminase. Mol Pharm 43: 380?387, 1993
  11. Caruso M, Panis Y, Gagandeep S, Houssin D, Salzmann JL, Klatzmann D: Regression of established macroscopic liver metastases afterin situ transduction of a suicide gene. Proc Natl Acad Sci USA 90: 7024?7028, 1993
  12. Moolten FL: Tumor chemosensitivity conferred by inserted Herpes simplex thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res 46: 5276?5281, 1986
  13. Moolten FL, Wells JM: Curability of tumors bearing Herpes thymidine kinase genes transferred by retroviral vectors. J Natl Cancer Inst 82: 297?300, 1990
  14. Moolten FL, Wells JM, Heyman RA, Evans RM: Lymphoma regression induced by ganciclovir in mice bearing a Herpes thymidine kinase transgene. Hum Gene Ther 1: 125?134, 1990
  15. Mullen CA, Kilstrup M, Blaese RM: Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine: a negative selection system. Proc Natl Acad Sci USA 89: 33?37, 1992
  16. Barba D, Hardin J, Ray J, Gage FH: Thymidine kinase-me-diated killing of rat brain tumors. J Neurosurg 79: 729?735, 1993
  17. Barba D, Hardin J, Sadelain M, Gage FH: Development of anti-tumor immunity following thymidine kinase-mediated killing of experimental brain tumors. Proc Natl Acad Sci USA 91: 4348?4352, 1994
  18. Chen SH, Shine HD, Goodman JC, Grossman RG, Woo SLC: Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transferin vivo. Proc Natl Acad Sci USA 91: 3054?3057, 1994
  19. Culver KW, Ram Z, Wallbridge S, Ishii H, Oldfield EH, Blaese RM:In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science 256: 1550?1552, 1992
  20. Ram Z, Culver KW, Walbridge S, Blaese RM, Oldfield EH:In situ retroviral-mediated gene transfer for the treatment of brain tumors in rats. Cancer Res 53: 83?88, 1993
  21. Colbere-Garapin F, Chousterman S, Horodniceanu F, Kourilsky P, Garapin AC: Cloning of the active thymidine kinase gene of Herpes simplex virus type 1 in Escherichia coli K12. Proc Natl Acad Sci USA 76: 3755?3758, 1979
  22. Chen C, Okayoma H: Calcium phosphate-mediated gene transfer: a highly efficient transfection system for stably transforming cells with plasmid DNA. Biotechniques 6: 632?638, 1988
  23. Benabid AL, Remy C, Chauvin C: Experimental models of rat brain tumors by stereotactic injection of C6 glioma and HTC hepatoma cell lines. In: Walker MD (eds) Biology of Brain Tumor, Martinus Nijhoff Publishers, Boston, pp 221?226, 1986
  24. Kobayashi N, Allen N, Clendenon NR, Ko LW: An improved rat brain-tumor model. J Neurosurg 53: 808?815, 1980
  25. Ezzedine ZD, Martuza RL, Platika D, Short MP, Malick A, Choi B, Breakefield XO: Selective killing of glioma cells in culture andin vivo by retrovirus transfer of the Herpes simplex virus thymidine kinase gene. New Biol 3: 608?614, 1991
  26. Takamiya Y, Short MP, Ezzedine ZD, Moolten FL, Breake-field XO, Martuza RL: Gene therapy of malignant brain tumors: a rat glioma line bearing the Herpes simplex virus type 1-thymidine kinase gene and wild type retrovirus kills other tumor cells. J Neurosci Res 33: 493?503, 1992
  27. Takamiya Y, Short MP, Moolten FL, Fleet C, Mineta T, Breakefield XO, Martuza RL: An experimental model of retrovirus gene therapy for malignant brain tumors. J Neurosurg 79: 104?110, 1993
Bibliographic reference Maron, A ; Gustin, Thierry ; Mottet, I. ; Demeure, R. ; Octave, Jean-Noël. Ganciclovir mediated regression of rat brain tumors expressing the herpes simplex virus thymidine kinase imaged by magnetic resonance.. In: Journal of neuro-oncology, Vol. 24, no. 3, p. 259-65 (1995)
Permanent URL http://hdl.handle.net/2078.1/23007