Abstract
The poor prognosis for patients with malignant gliomas calls for novel therapeutic approaches in this field of oncology. At present, involved-field radiotherapy is the single most effective treatment. Most of the currently available chemotherapy strategies fail because of the resistance of glioma cells to cytotoxic agents. Mutations of tumor suppressor genes (such as Rb or p53) or enhanced expression of oncogenes (such as bcl-2 or bcl-X), both common features of malignant gliomas, may inhibit the efficient killing of tumor cells by cytotoxic drugs or radiotherapy. Because activation of apoptotic cell death cascades is now considered to be a powerful instrument to rapidly and specifically induce the death of target cells, many researchers are seeking ways to utilize the apoptotic signaling pathway for therapeutic purposes.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Thompson, C. B. (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267, 1456–1462.
Smith, C. A., Farrah, T., and Goodwin, R. G. (1994) TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 76, 959–962.
Tartaglia, L. A., Ayres, T. M., Wong, G. H., and Goeddel, D. V. (1993) Novel domain within the 55 kd TNF receptor signals cell death. Cell 74, 845–853.
Banner, D. W., D’Arcy, A., Janes, W., Gentz, R., Schoenfeld, H. J., Broger, C., Loetscher, H., and Lesslauer, W. (1993) Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation. Cell 73, 431–445.
Krammer, P. H., Dhein, J., Walczak, H., Behrmann, I., Mariani, S., Matiba, B., et al. (1994) Role of APO-1-mediated apoptosis in the immune system. Immunol. Rev. 142, 175–191.
Schulze-Osthoff, K., Ferrari, D., Los, M., Wesselborg, S., and Peter, M. E. (1998) Apoptosis signaling by death receptors. Eur. J. Biochem. 254, 439–459.
Ashkenazi, A. and Dixit, V. M. (1998) Death receptors: signaling and modulation. Science 281, 1305–1308.
Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., and Nagata, S. (1998) A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391, 43–50.
Yoshida, J., Wakabayashi, T., Mizuno, M., Sugita, K., Yoshida, T., Hori, S., et al. (1992) Clinical effect of intra-arterial tumor necrosis factor for malignant glioma. J. Neurosurg. 77, 78–83.
Bodmer, J. L., Burns, K., Schneider, P., Hofmann, K., Steiner, V., Thome, M., et al. (1997) TRAMP, a novel apoptosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas(Apo-1/CD95). Immunity 6, 79–88.
Trauth, B. C., Klas, C., Peters, A. M., Matzku, S., Moller, P., Falk, W., Debatin, K. M., and Krammer, P. H. (1989) Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 245, 301–305.
Yonehara, S., Ishii, A., and Yonehara, M. (1989) A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J. Exp. Med. 169, 1747–1756.
Nagata, S. (1997) Apoptosis by death factor. Cell 88, 355–365.
Chinnaiyan, A. M., O’Rourke, K., Tewari, M., and Dixit, V. M. (1995) FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81, 505–512.
Boldin, M. P., Goncharov, T. M., Goltsev, Y. V., and Wallach, D. (1996) Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 85, 803–815.
Muzio, M., Chinnaiyan, A. M., Kischkel, F. C., O’Rourke, K., Shevchenko, A., Ni, J., et al. (1996) FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell 85, 817–827.
Kischkel, F. C., Hellbardt, S., Behrmann, I., Germer, M., Pawlita, M., Krammer, P. H., and Peter, M. E. (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 14, 5579–5588.
Medema, J. P., Scaffidi, C., Kischkel, F. C., Shevchenko, A., Mann, M., Krammer, P. H., and Peter, M. E. (1997) FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J. 16, 2794–2804.
Nicholson, D. W. and Thornberry, N. A. (1997) Caspases: killer proteases. Trends Biochem. Sci. 22, 299–306.
Reed, J. C. (1997) Double identity for proteins of the Bcl-2 family. Nature 387, 773–776.
Weller, M., Malipiero, U., Aguzzi, A., Reed, J. C., and Fontana, A. (1995) Protooncogene bd-2 gene transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation. J. Clin. Invest. 95, 2633–2643.
Itoh, N., Tsujimoto, Y., and Nagata, S. (1993) Effect of bcl-2 on Fas antigen-mediated cell death. J. Immunol. 151, 621–627.
Roy, N., Mahadevan, M. S., McLean, M., Shutler, G., Yaraghi, Z., Farahani, R., et al. (1995) Gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 80, 167–178.
Duckett, C. S., Nava, V. E., Gedrich, R. W., Clem, R. J., Dongen, J. L., Gilfillan, M. C., et al. (1996) A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J. 15, 2685–2694.
Liston, P., Roy, N., Tamai, K., Lefebvre, C., Baird, S., Cherton Horvat, G., et al. (1996) Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 379, 349–353.
Ambrosini, G., Adida, C., and Altieri, D. C. (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat. Med 3, 917–921.
Thome, M., Schneider, P., Hofmann, K., Fickenscher, H., Meinl, E., Neipel, F., et al. (1997) Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386, 517–521.
Pitti, R. M., Marsters, S. A., Lawrence, D. A., Roy, M., Kischkel, F. C., Dowd, P., et al. (1998) Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 396, 699–703.
Weller, M., Kleihues, P., Dichgans, J., and Ohgaki, H. (1998) CD95 ligand: lethal weapon against malignant glioma? Brain Pathol. 8, 285–293.
Leithäuser, F., Dhein, J., Mechtersheim, G., Koretz, K., Brüderlein, S., Henne, C., et al. (1993) Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor superfamily, in normal and neoplastic cells. Lab. Invest. 69, 415–429.
French, L. E., Hahne, M., Viard, I., Radlgruber, G., Zanone, R., Becker, K., Muller, C., and Tschopp, J. (1996) Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover. J. Cell Biol. 133, 335–343.
Weller, M., Frei, K., Groscurth, P., Krammer, P. H., Yonekawa, Y., and Fontana, A. (1994) Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines. J. Clin. Invest. 94, 954–964.
Tachibana, O., Nakazawa, H., Lampe, J., Watanabe, K., Kleihues, P., and Ohgaki, H. (1995) Expression of Fas/APO-1 during the progression of astrocytomas. Cancer Res. 55, 5528–5530.
Gratas, C., Tohma, Y., Meir, E., Klein, M., Tenan, M., Ishii, N., et al. (1997) Fas ligand expression in glioblastoma cell lines and primary astrocytic brain tumors. Brain Pathol. 7, 863–869.
Tohma, Y., Gratas, C., Meir, E. G., Desbaillets, I., Tenan, M., Tachibana, O., Kleihues, P., and Ohgaki, H. (1998) Necrogenesis and Fas/APO-1 (CD95) expression in primary (novo) and secondary glioblastomas. J. Neuropathol. Exp. Neurol. 57, 239–245.
Frei, K., Ambar, B., Adachi, N., Yonekawa, Y., and Fontana, A. (1998) Ex vivo malignant glioma cells are sensitive to Fas (CD95/APO-1) ligand-mediated apoptosis. J. Neuroimmunol. 87, 105–113.
Tachibana, O., Lampe, J., Kleihues, P., and Ohgaki, H. (1996) Preferential expression of Fas/APO 1 (CD95) and apoptotic cell death in perinecrotic cells of glioblastoma multiforme. Acta Neuropathol. (Berl.) 92, 431–434.
Weller, M., Weinstock, C., Will, C., Wagenknecht, B., Dichgans, J., Lang, F., and Gulbins, E. (1997) CD95-dependent T cell killing by glioma cells expressing CD95L: more on tumor immune escape, the CD95 counterattack, and the immune privilege of the brain. Cell Physiol. Biochem. 7, 282–288.
Saas, P., Walker, P. R., Hahne, M., Quiquerez, A. L., Schnuriger, V., Perrin, G., et al. (1997) Fas ligand expression by astrocytoma in vivo: maintaining immune privilege in the brain? J. Clin. Invest. 99, 1173–1178.
Roth, W., Fontana, A., Trepel, M., Reed, J. C., Dichgans, J., and Weller, M. (1997) Immunochemotherapy of malignant glioma: synergistic activity of CD95 ligand and chemotherapeutics. Cancer Immunol. Immunother 44, 55–63.
Zipp, F., Martin, R., Lichtenfels, R., Roth, W., Dichgans, J., Krammer, P. H., and Weller, M. (1997) Human autoreactive and foreign antigen-specific T cells resist apoptosis induced by soluble recombinant CD95 ligand. J. Immunol. 159, 2108–2115.
Schneider, P., Holler, N., Bodmer, J. L., Hahne, M., Frei, K., Fontana, A., Tschopp, J. (1998) Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity. J. Exp. Med. 187, 1205–1213.
Weller, M., Malipiero, U., Rensing Ehl, A., Barr, P. J., and Fontana, A. (1995) Fas/APO-1 gene transfer for human malignant glioma. Cancer Res. 55, 2936–2944.
Wagenknecht, B., Schulz, J. B., Gulbins, E., and Weller, M. (1998) Crm-A, bcl-2 and NDGA inhibit CD95L-induced apoptosis of malignant glioma cells at the level of caspase 8 processing. Cell Death Differ. 5, 894–900.
Krajewski, S., Krajewska, M., Ehrmann, J., Sikorska, M., Lach, B., Chatten, J., and Reed, J. C. (1997) Immunohistochemical analysis of Bcl-2, Bel-X, Mcl-1, and Bax in tumors of central and peripheral nervous system origin. Am. J. Pathol. 150, 805–814.
Roth, W., Grimmel, C., Rieger, L., Strik, H., Takayama, S., Pichgans, J., et al. (2000) Bag-1 and bcl-2 gene transfer in malignant glioma: modulation of cell cycle regulation and aptosis. Brain Pathol. 10, 223–234.
Weller, M., Rieger, J., Grimmel, C., Meir, E. G., Tribolet, N., Krajewski, S., et al. (1998) Predicting chemoresistance in human malignant glioma cells: the role of molecular genetic analyses. Int. J. Cancer 79, 640–644.
Rensing-Ehl, A., Frei, K., Flury, R., Matiba, B., Mariani, S. M., Weller, M., et al. (1995) Local Fas/APO-1 (CD95) ligand-mediated tumor cell killing in vivo. Eur. J. Immunol. 25, 2253–2258.
Arai, H., Gordon, D., Nabel, E.G., and Nabel, G. J. (1997) Gene transfer of Fas ligand induces tumor regression in vivo. Proc. Natl. Acad. Sci. U.S.A. 94, 13,862–13, 867.
Seino, K., Kayagaki, N., Okumura, K., and Yagita, H. (1997) Antitumor effect of locally produced CD95 ligand. Nat. Med. 3, 165–170.
Yu, J. S., Sena Esteves, M., Paulus, W., Breakefield, X. O., and Reeves, S. A. (1996) Retroviral delivery and tetracycline-dependent expression of IL-lbeta-converting enzyme (ICE) in a rat glioma model provides controlled induction of apoptotic death in tumor cells. Cancer Res. 56, 5423–5427.
Kondo, S., Tanaka, Y., Kondo, Y., Ishizaka, Y., Hitomi, M., Haqqi, T., et al. (1998) Retro-viral transfer of CPP32beta gene into malignant gliomas in vitro and in vivo. Cancer Res. 58, 962–967.
Kondo, S., Ishizaka, Y., Okada, T., Kondo, Y., Hitomi, M., Tanaka, Y., et al. (1998) FADD gene therapy for malignant gliomas in vitro and in vivo. Hum. Gene Ther. 9, 1599–1608.
Roth, W., Wagenknecht, B., Grimmel, C., Dichgans, J., and Weller, M. (1998) Taxolmediated augmentation of CD95 ligand-induced apoptosis of human malignant glioma cells. Association with bc1–2 phosphorylation but neither activation of p53 nor G2/M cell cycle arrest. Br. J. Cancer 77, 404–411.
Winter, S., Roth, W., Dichgans, J., and Weller, M. (1998) Synergy of CD95 ligand and teniposide: no role of cleavable complex formation and enhanced CD95 expression. Eur. J. Pharmacol. 352, 111–115.
Winter, S. and Weller, M. (1998) Potentiation of CD95L-induced apoptosis of human malignant glioma cells by topotecan involves inhibition of RNA synthesis but not changes in CD95 or CD95L protein expression. J. Pharmacol. Exp. Ther. 286, 1374–1382.
Weller, M., Winter, S., Schmidt, C., Esser, P., Fontana, A., Dichgans, J., and Groscurth, P. (1997) Topoisomerase-I inhibitors for human malignant glioma: differential modulation of p53, p21, bax and bc1–2 expression and of CD95-mediated apoptosis by camptothecin and beta-lapachone. Int. J. Cancer 73, 707–714.
Hueber, A., Durka, S., and Weller, M. (1998) CD95-mediated apoptosis: no variation in cellular sensitivity during cell cycle progression. FEBS Lett. 432, 155–157.
Micheau, O., Solary, E., Hammann, A., Martin, F., and Dimanche-Boitrel, M. T. (1997) Sensitization of cancer cells treated with cytotoxic drugs to fas-mediated cytotoxicity. J. Natl. Cancer Inst. 89, 783–789.
Müller, M., Strand, S., Hug, H., Heinemann, E. M., Walczak, H., Hofmann, W. J., et al. (1997) Drug-induced apoptosis in hepatoma cells is mediated by the CD95 (APO-1/Fas) receptor/ligand system and involves activation of wild-type p53. J. Clin. Invest. 99, 403–413.
Friesen, C., Herr, I., Krammer, P. H., and Debatin, K. M. (1996) Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nat. Med. 2, 574–577.
Fulda, S., Sieverts, H., Friesen, C., Herr, I., and Debatin, K.M. (1997) The CD95 (APO-1/ Fas) system mediates drug-induced apoptosis in neuroblastoma cells. Cancer Res. 57, 3823–3829.
Eischen, C. M., Kottke, T. J., Martins, L. M., Basi, G. S., Tung, J. S., Earnshaw, W. C., Leibson, P. J., and Kaufmann, S. H. (1997) Comparison of apoptosis in wild-type and Fas-resistant cells: chemotherapy-induced apoptosis is not dependent on Fas/Fas ligand interactions. Blood 90, 935–943.
Gamen, S., Anel, A., Lasierra, P., Alava, M. A., Martinez Lorenzo, M. J., Pineiro, A., and Naval, J. (1997) Doxorubicin-induced apoptosis in human T-cell leukemia is mediated by caspase-3 activation in a Fas-independent way. FEBS Lett. 417, 360–364.
Villunger, A., Egle, A., Kos, M., Hartmann, B. L., Geley, S., Kofler, R., and Greil, R. (1997) Drug-induced apoptosis is associated with enhanced Fas (Apo-1/CD95) ligand expression but occurs independently of Fas (Apo-1/CD95) signaling in human T-acute lymphatic leukemia cells. Cancer Res. 57, 3331–3334.
Ogasawara, J., Watanabe Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., et al. (1993) Lethal effect of the anti-Fas antibody in mice. Nature 364, 806–809.
Nagata, S. (1996) Fas ligand and immune evasion. Nat. Med. 2, 1306–1307.
Weller, M. and Fontana, A. (1995) The failure of current immunotherapy for malignant glioma. Tumor-derived TGF-(3, T-cell apoptosis, and the immune privilege of the brain. Brain Res. Rev. 21, 128–151.
Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C. P., Nicholl, J. K., et al. (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3, 673–682.
Pitti, R. M., Marsters, S. A., Ruppert, S., Donahue, C. J., Moore, A., and Ashkenazi, A. (1996) Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J. Biol. Chem. 271, 12,687–12, 690.
Marsters, S. A., Pitti, R. M., Donahue, C. J., Ruppert, S., Bauer, K. D., and Ashkenazi, A. (1996) Activation of apoptosis by Apo-2 ligand is independent of FADD but blocked by CrmA. Curr. Biol. 6, 750–752.
Pan, G., O’Rourke, K., Chinnaiyan, A. M., Gentz, R., Ebner, R., Ni, J., and Dixit, V. M. (1997) The receptor for the cytotoxic ligand TRAIL. Science 276, 111–113.
Pan, G., Ni, J., Wei, Y. F., Yu, G., Gentz, R., and Dixit, V. M. (1997) Antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277, 815–818.
Chaudhary, P. M., Eby, M., Jasmin, A., Bookwalter, A., Murray, J., and Hood, L. (1997) Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway. Immunity 7, 821–830.
Sheridan, J. P., Marsters, S. A., Pitti, R. M., Gurney, A., Skubatch, M., Baldwin, D., et al. (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277, 818–821.
Schneider, P., Bodmer, J. L., Thome, M., Hofmann, K., Holler, N., and Tschopp, J. (1997) Characterization of two receptors for TRAIL. FEBS Lett. 416, 329–334.
Degli-Esposti, M. A., Smolak, P. J., Walczak, H., Waugh, J., Huang, C. P., DuBose, R. F., Goodwin, R. G., and Smith, C. A. (1997) Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J. Exp. Med. 186, 1165–1170.
Marsters, S. A., Sheridan, J. P., Pitti, R. M., Huang, A., Skubatch, M., Baldwin, D., et al. (1997) Novel receptor for Apo2L/TRAIL contains a truncated death domain. Curr. Biol. 7, 1003–1006.
Degli-Esposti, M. A., Dougall, W. C., Smolak, P. J., Waugh, J. Y., Smith, C. A., and Goodwin, R. G. (1997) The novel receptor TRAIL-R4 induces NF-KB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity 7, 813–820.
Pan, G., Ni, J., Yu, G., Wei, Y. F., and Dixit, V. M. (1998) TRUNDD, a new member of the TRAIL receptor family that antagonizes TRAIL signaling. FEBS Lett. 424, 41–45.
Glaser, T., Wagenknecht, B., Groscurth, P., Krammer, P. H., and Weller, M. (1999) Death ligand/receptor-independent caspase activation mediates drug-induced cytotoxic cell death in human malignant glioma cells. Oncogene 18, 5044–5053.
Golstein, P. (1997) Cell death: TRAIL and its receptors. Curr. Biol. 7, R750 — R753.
Mongkolsapaya, J., Cowper, A. E., Xu, X. N., Morris, G., McMichael, A. J., Bell, J. I., and Screaton, G. R. (1998) Lymphocyte inhibitor of TRAIL (TNF-related apoptosis-inducing ligand): a new receptor protecting lymphocytes from the death ligand TRAIL. J. Immunol. 160, 3–6.
Griffith, T. S., Chin, W. A., Jackson, G. C., Lynch, D. H., and Kubin, M. Z. (1998) Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. J. Immunol. 161, 2833–2840.
Walczak, H., Degli Esposti, M. A., Johnson, R. S., Smolak, P. J., Waugh, J. Y., Boiani, N., et al. (1997) TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J. 16, 5386–5397.
Schneider, P., Thome, M., Burns, K., Bodmer, J. L., Hofmann, K., Kataoka, T., Holler, N., and Tschopp, J. (1997) TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. Immunity 7, 831–836.
MacFarlane, M., Ahmad, M., Srinivasula, S. M., Fernandes Alnemri, T., Cohen, G. M., and Alnemri, E. S. (1997) Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL. J. Biol. Chem. 272, 25,417–25, 420.
Griffith, T. S. and Lynch, D. H. (1998) TRAIL: a molecule with multiple receptors and control mechanisms. Curr. Opin. Immunol. 10, 559–563.
Rieger, J., Naumann, U., Glaser, T., Ashkenazi, A., and Weller, M. (1998) APO2 ligand: a novel lethal weapon against malignant glioma? FEBS Lett. 427, 124–128.
Rieger, J., Ohgaki, H., Kleihues, P., and Weller, M. (1999) Human astrocytic brain tumors express APO2L/TRAIL. Acta Neuropathol. 97, 1–4.
Snell, V., Clodi, K., Zhao, S., Goodwin, R., Thomas, E. K., Morris, S. W., et al. (1997) Activity of TNF-related apoptosis-inducing ligand (TRAIL) in haematological malignancies. Br. J. Haematol. 99, 618–624.
Thomas, W. D. and Hersey, P. (1998) TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in Fas ligand-resistant melanoma cells and mediates CD4 T cell killing of target cells. J. Immunol. 161, 2195–2200.
Mariani, S. M., Matiba, B., Armandola, E. A., and Krammer, P. H. (1997) Interleukin 1 beta-converting enzyme related proteases/caspases are involved in TRAIL-induced apoptosis of myeloma and leukemia cells. J. Cell Biol. 137, 221–229.
Roth, W., Wagenknecht, B., Dichgans, J., and Weller, M. (1998) Interferon-a enhances CD95L-induced apoptosis of human malignant glioma cells. J. Neuroimmunol. 87, 121–129.
Weller, M., Schmidt, C., Roth, W., and Dichgans, J. (1997) Chemotherapy of human malignant glioma: prevention of efficacy by dexamethasone? Neurology 48, 1704–1709.
Naumann, U., Durka, S., and Weller, M. (1998) Dexamethasone-mediated protection from drug cytotoxicity: association with p21 WAF1/CIP1 protein accumulation? Oncogene 17, 1567–1575.
Fujisawa, K., Asahara, H., Okamoto, K., Aono, H., Hasunuma, T., Kobata, T., et al. (1996) Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-1 tax transgenic mice. J. Clin. Invest. 98, 271–278.
Zhang, H., Yang, Y., Horton, J. L., Samoilova, E. B., Judge, T. A., Turka, L. A., Wilson, J. M., and Chen, Y. (1997) Amelioration of collagen-induced arthritis by CD95 (Apo-1/Fas)ligand gene transfer. J. Clin. Invest. 100, 1951–1957.
Richardson, B. C., Lalwani, N. D., Johnson, K. J., and Marks, R. M. (1994) Fas ligation triggers apoptosis in macrophages but not endothelial cells. Eur. J. Immunol. 24, 2640–2645.
Walczak, H., Miller, R. E., Ariail, K., Gliniak, B., Griffith, T. S., Kubin, M., et al. (1999) Tumoricidal activity of tumor necrosis factor-related aptosis-inducing ligand in vivo. Nat. Med. 5, 159–163.
Ashkenazi, A., Pai, R. C., Fong, S., Leung, S., Lawrence, D. A., Marsters, S. A., et al. (1999) Safety and antitumor activity of recombinant soluble Apo2L ligand. J. Clin. Invest. 104, 155–162.
Roth, W., Isenmann, S., Naumann, U., Kugler, S., Bahr, M., Dichgans, J., et al. (1999) Locoregional Apo2L/TRAIL eradicates intracranial human malignant glioma xenografts in athymic mice in the absence of neurotoxicity. Biochem. Res. Commun. 265, 479–483.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer Science+Business Media New York
About this chapter
Cite this chapter
Roth, W., Weller, M. (2001). Death Ligand/Death Receptor-Mediated Apoptosis for Treatment of Brain Tumors. In: Liau, L.M., Becker, D.P., Cloughesy, T.F., Bigner, D.D. (eds) Brain Tumor Immunotherapy. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-035-3_16
Download citation
DOI: https://doi.org/10.1007/978-1-59259-035-3_16
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-110-3
Online ISBN: 978-1-59259-035-3
eBook Packages: Springer Book Archive