TGF-β2 signaling in high-grade gliomas

Current Pharmaceutical Biotechnology

Volumn 12, Issue 12, 2011, Pages 2150-2157

  Hau, Peter ^a   Jachimczak, Piotr ^b   Schlaier, Jürgen ^a   Bogdahn, Ulrich ^a  

^a UNIVERSITY OF REGENSBURG   (Germany)

^b Antisense Pharma   (Germany)

Author keywords

Antisense; Gliomagenesis; High grade glioma; Oligonucleotide; Signaling pathway; Transforming growth factor beta

Indexed keywords

CARMUSTINE; CD133 ANTIGEN; FIBROBLAST GROWTH FACTOR 2; GAMMA INTERFERON; GELATINASE A; GELATINASE B; HLA DR ANTIGEN; INTERLEUKIN 10; INTERLEUKIN 2; INTERLEUKIN 6; LOMUSTINE; MESSENGER RNA; PLATELET DERIVED GROWTH FACTOR; PROCARBAZINE; SMAD PROTEIN; TEMOZOLOMIDE; TRABEDERSEN; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2; TRANSFORMING GROWTH FACTOR BETA3; VASCULOTROPIN; VINCRISTINE;

ANTISENSE THERAPY; ARTICLE; B LYMPHOCYTE ACTIVATION; CANCER COMBINATION CHEMOTHERAPY; CANCER GENE THERAPY; CANCER RADIOTHERAPY; CANCER REGRESSION; CANCER SURGERY; CANCER SURVIVAL; CARCINOGENESIS; CELL PROLIFERATION; CYTOKINE PRODUCTION; CYTOTOXIC T LYMPHOCYTE; DISEASE SEVERITY; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG TARGETING; GENE EXPRESSION; GENETIC TRANSCRIPTION; GLIOBLASTOMA; GLIOMA; GLIOMAGENESIS; HUMAN; IMMUNE DEFICIENCY; MULTIMODALITY CANCER THERAPY; MULTIPLE CYCLE TREATMENT; NONHUMAN; RECURRENT CANCER; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; SURVIVAL RATE; T LYMPHOCYTE ACTIVATION; TREATMENT RESPONSE;

ANIMALS; ANTINEOPLASTIC AGENTS; BRAIN NEOPLASMS; GLIOMA; HUMANS; OLIGODEOXYRIBONUCLEOTIDES; THIONUCLEOTIDES; TRANSFORMING GROWTH FACTOR BETA2;

EID: 84855245343     PISSN: 13892010     EISSN: 18734316     Source Type: Journal    
DOI: 10.2174/138920111798808347     Document Type: Article

References (104)

1. Bonafoux, D.; Lee, W.C. Strategies for TGF-beta modulation: a review of recent patents. Expert Opin. Ther. Pat., 2009, 19(12), 1759-1769.
2. Chen, R.; Nishimura, M.C.; Bumbaca, S.M.; Kharbanda, S.; Forrest, W.F.; Kasman, I.M.; Greve, J.M.; Soriano, R.H.; Gilmour, L.L.; Rivers, C.S.; Modrusan, Z.; Nacu, S.; Guerrero, S.; Edgar, K.A.; Wallin, J.J.; Lamszus, K.; Westphal, M.; Heim, S.; James, C.D.; Vandenberg, S.R.; Costello, J.F.; Moorefield, S.; Cowdrey, C.J.; Prados, M.; Phillips, H.S. A hierarchy of self-renewing tumorinitiating cell types in glioblastoma. Cancer Cell, 2010, 17(4), 362-375.
3. Mourad, P.D.; Farrell, L.; Stamps, L.D.; Chicoine, M.R.; Silbergeld, D.L. Why are systemic glioblastoma metastases rare? Systemic and cerebral growth of mouse glioblastoma. Surg. Neurol., 2005. 63(6), 511-519.discussion 519.
4. Kleihues, P.; Louis, D.N.; Scheithauer, B.W.; Rorke, L.B.; Reifenberger, G.; Burger, P.C.; Cavenee, W.K. The WHO classification of tumors of the nervous system. J. Neuropathol. Exp. Neurol., 2002. 61(3), 215-225.discussion 226-229.
5. Stupp, R.; Mason, W.P.; Van Den Bent, M.J.; Weller, M.; Fisher, B.; Taphoorn, M.J.; Belanger, K.; Brandes, A.A.; Marosi, C.; Bogdahn, U.; Curschmann, J.; Janzer, R.C.; Ludwin, S.K.; Gorlia, T.; Allgeier, A.; Lacombe, D.; Cairncross, J.G.; Eisenhauer, E.; Mirimanoff, R.O. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med., 2005. 352(10), 987-996.
6. Stupp, R.; Hegi, M.E.; Mason, W.P.; Van Den Bent, M.J.; Taphoorn, M.J.; Janzer, R.C.; Ludwin, S.K.; Allgeier, A.; Fisher, B.; Belanger, K.; Hau, P.; Brandes, A.A.; Gijtenbeek, J.; Marosi, C.; Vecht, C.J.; Mokhtari, K.; Wesseling, P.; Villa, S.; Eisenhauer, E.; Gorlia, T.; Weller, M.; Lacombe, D.; Cairncross, J.G.; Mirimanoff, R.O. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol., 2009. 10(5), 459-466.
7. Wen, P.Y.; Brandes, A.A. Treatment of recurrent high-grade gliomas. Curr. Opin. Neurol., 2009, 22(6),657-664.
8. Flanders, K.C.; Ludecke, G.; Engels, S.; Cissel, D.S.; Roberts, A.B.; Kondaiah, P.; Lafyatis, R.; Sporn, M.B.; Unsicker, K. Localization and actions of transforming growth factor-beta s in the embryonic nervous system. Development, 1991. 113(1), 183-191.
9. Miller, M.W. Expression of transforming growth factor-beta in developing rat cerebral cortex: effects of prenatal exposure to ethanol. J. Comp. Neurol., 2003, 460(3), 410-424.
10. Pelton, R.W.; Saxena, B.; Jones, M.; Moses, H.L.; Gold, L.I. Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development. J. Cell Biol., 1991, 115(4), 1091-1105.
11. Roberts, A.B. Molecular and cell biology of TGF-beta. Miner Electrolyte Metab., 1998, 24(2-3), 111-119.
12. Rich, J.N. The role of transforming growth factor-beta in primary brain tumors. Front Biosci., 2003, 8, e245-260.
13. Derynck, R.; Goeddel, D.V.; Ullrich, A.; Gutterman, J.U.; Williams, R.D.; Bringman, T.S.; Berger, W.H. Synthesis of messenger RNAs for transforming growth factors alpha and beta and the epidermal growth factor receptor by human tumors. Cancer Res., 1987, 47(3), 707-712.
14. Jachimczak, P.; Bogdahn, U.; Schneider, J.; Behl, C.; Meixensberger, J.; Apfel, R.; Dorries, R.; Schlingensiepen, K.H.; Brysch, W. The effect of transforming growth factor-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides in reversing cellular immunosuppression in malignant glioma. J. Neurosurg., 1993, 78(6), 944-951.
15. Kjellman, C.; Olofsson, S.P.; Hansson, O.; Von Schantz, T.; Lindvall, M.; Nilsson, I.; Salford, L.G.; Sjogren, H.O.; Widegren, B. Expression of TGF-beta isoforms, TGF-beta receptors, and SMAD molecules at different stages of human glioma. Int. J. Cancer, 2000. 89(3), 251-258.
16. Schlingensiepen, K.H.; Schlingensiepen, R.; Steinbrecher, A.; Hau, P.; Bogdahn, U.; Fischer-Blass, B.; Jachimczak, P. Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009. Cytokine Growth Factor Rev., 2006. 17(1-2), 129-139.
17. Wick, W.; Platten, M.; Weller, M. Glioma cell invasion: regulation of metalloproteinase activity by TGF-beta. J. Neurooncol., 2001. 53(2), 177-185.
18. Lopez-Casillas, F.; Payne, H.M.; Andres, J.L.; Massague, J. Betaglycan can act as a dual modulator of TGF-beta access to signaling receptors: mapping of ligand binding and GAG attachment sites. J. Cell Biol., 1994. 124(4), 557-568.
19. Massague, J.; Seoane, J.; Wotton, D. Smad transcription factors. Genes Dev., 2005. 19(23), 2783-2810.
20. Derynck, R.; Zhang, Y.E. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature, 2003. 425(6958), 577-584.
21. Moustakas, A.; Heldin, C.H. Non-Smad TGF-beta signals. J. Cell Sci., 2005. 118(Pt 16), 3573-3584.
22. Padua, D.; Massague, J. Roles of TGFbeta in metastasis. Cell Res., 2009. 19(1), 89-102.
23. Aigner, L.; Bogdahn, U. TGF-beta in neural stem cells and in tumors of the central nervous system. Cell Tissue Res., 2008. 331(1), 225-241.
24. Nickl-Jockschat, T.; Arslan, F.; Doerfelt, A.; Bogdahn, U.; Bosserhoff, A.; Hau, P. An imbalance between Smad and MAPK pathways is responsible for TGF-beta tumor promoting effects in high-grade gliomas. Int. J. Oncol., 2007, 30(2), 499-507.
25. Seoane, J. Escaping from the TGFbeta anti-proliferative control. Carcinogenesis, 2006, 27(11), 2148-2156.
26. Platten, M.; Wick, W.; Weller, M. Malignant glioma biology: role for TGF-beta in growth, motility, angiogenesis, and immune escape. Microsc. Res. Tech., 2001, 52(4), 401-410.
27. Rich, J.; Borton, A.; Wang, X.; Platten, M.; Wick, W.; Weller, M. Transforming growth factor-beta signaling in cancer. Microsc. Res. Tech., 2001, 52(4), 363-373.
28. Siegel, P.M.; Massague, J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat. Rev. Cancer, 2003, 3(11), 807-821.
29. Wakefield, L.M.; Roberts, A.B. TGF-beta signaling: positive and negative effects on tumorigenesis. Curr. Opin. Genet. Dev., 2002. 12(1), 22-29.
30. Wachs, F.P.; Winner, B.; Couillard-Despres, S.; Schiller, T.; Aigner, R.; Winkler, J.; Bogdahn, U.; Aigner, L. Transforming growth factor-beta1 is a negative modulator of adult neurogenesis. J. Neuropathol. Exp. Neurol., 2006. 65(4), 358-370.
31. Jachimczak, P.; Hessdorfer, B.; Fabel-Schulte, K.; Wismeth, C.; Brysch, W.; Schlingensiepen, K.H.; Bauer, A.; Blesch, A.; Bogdahn, U. Transforming growth factor-beta-mediated autocrine growth regulation of gliomas as detected with phosphorothioate antisense oligonucleotides. Int. J. Cancer, 1996. 65(3), 332-337.
32. Jennings, M.T.; Maciunas, R.J.; Carver, R.; Bascom, C.C.; Juneau, P.; Misulis, K.; Moses, H.L. TGF beta 1 and TGF beta 2 are potential growth regulators for low-grade and malignant gliomas in vitro: evidence in support of an autocrine hypothesis. Int. J. Cancer, 1991, 49(1), 129-139.
33. Bruna, A.; Darken, R.S.; Rojo, F.; Ocana, A.; Penuelas, S.; Arias, A.; Paris, R.; Tortosa, A.; Mora, J.; Baselga, J.; Seoane, J. High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell, 2007, 11(2), 147-160.
34. Fontana, A.; Bodmer, S.; Frei, K.; Malipiero, U.; Siepl, C. Expression of TGF-beta 2 in human glioblastoma: a role in resistance to immune rejection? Ciba. Found Symp., 1991, 157, 232-238;discussion 238-241.
35. Kuppner, M.C.; Hamou, M.F.; Sawamura, Y.; Bodmer, S.; De Tribolet, N. Inhibition of lymphocyte function by glioblastomaderived transforming growth factor beta 2. J. Neurosurg., 1989, 71(2), 211-217.
36. Maxwell, M.; Galanopoulos, T.; Neville-Golden, J.; Antoniades, H.N. Effect of the expression of transforming growth factor-beta 2 in primary human glioblastomas on immunosuppression and loss of immune surveillance. J. Neurosurg., 1992. 76(5), 799-804.
37. Bodmer, S.; Huber, D.; Heid, I.; Fontana, A. Human glioblastoma cell derived transforming growth factor-beta 2: evidence for secretion of both high and low molecular weight biologically active forms. J. Neuroimmunol., 1991. 34(1), 33-42.
38. Tada, T.; Yabu, K.; Kobayashi, S. Detection of active form of transforming growth factor-beta in cerebrospinal fluid of patients with glioma. Jpn. J. Cancer Res., 1993, 84(5), 544-548.
39. Frankel, B.; Longo, S.L.; Ryken, T.C. Human astrocytomas coexpressing Fas and Fas ligand also produce TGFbeta2 and Bcl-2. J. Neurooncol., 1999, 44(3), 205-212.
40. Tsushima, H.; Ito, N.; Tamura, S.; Matsuda, Y.; Inada, M.; Yabuuchi, I.; Imai, Y.; Nagashima, R.; Misawa, H.; Takeda, H.; Matsuzawa, Y.; Kawata, S. Circulating transforming growth factor beta 1 as a predictor of liver metastasis after resection in colorectal cancer. Clin. Cancer Res., 2001, 7(5), 1258-1262.
41. Schneider, T.; Sailer, M.; Ansorge, S.; Firsching, R.; Reinhold, D. Increased concentrations of transforming growth factor beta1 and beta2 in the plasma of patients with glioblastoma. J. Neurooncol., 2006, 79(1), 61-65.
42. Fontana, A.; Hengartner, H.; De Tribolet, N.; Weber, E. Glioblastoma cells release interleukin 1 and factors inhibiting interleukin 2-mediated effects. J. Immunol., 1984, 132(4), 1837-1844.
43. De Martin, R.; Haendler, B.; Hofer-Warbinek, R.; Gaugitsch, H.; Wrann, M.; Schlusener, H.; Seifert, J.M.; Bodmer, S.; Fontana, A.; Hofer, E. Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-beta gene family. EMBO J., 1987, 6(12), 3673-3677.
44. Wrann, M.; Bodmer, S.; De Martin, R.; Siepl, C.; Hofer-Warbinek, R.; Frei, K.; Hofer, E.; Fontana, A. T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta. EMBO J., 1987, 6(6), 1633-1636.
45. Bodmer, S.; Strommer, K.; Frei, K.; Siepl, C.; De Tribolet, N.; Heid, I.; Fontana, A. Immunosuppression and transforming growth factor-beta in glioblastoma. Preferential production of transforming growth factor-beta 2. J. Immunol., 1989, 143(10), 3222-3229.
46. Brooks, W.H.; Netsky, M.G.; Normansell, D.E.; Horwitz, D.A. Depressed cell-mediated immunity in patients with primary intracranial tumors. Characterization of a humoral immunosuppressive factor. J. Exp. Med., 1972. 136(6), 1631-1647.
47. Darley, R.; Morris, A.; Passas, J.; Bateman, W. Interactions between interferon gamma and retinoic acid with transforming growth factor beta in the induction of immune recognition molecules. Cancer Immunol. Immunother., 1993. 37(2), 112-118.
48. Fontana, A.; Constam, D.B.; Frei, K.; Malipiero, U.; Pfister, H.W. Modulation of the immune response by transforming growth factor beta. Int. Arch. Allergy Immunol., 1992, 99(1), 1-7.
49. Kehrl, J.H.; Roberts, A.B.; Wakefield, L.M.; Jakowlew, S.; Sporn, M.B.; Fauci, A.S. Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. J. Immunol., 1986, 137(12), 3855-3860.
50. Kehrl, J.H.; Wakefield, L.M.; Roberts, A.B.; Jakowlew, S.; Alvarez-Mon, M.; Derynck, R.; Sporn, M.B.; Fauci, A.S. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J. Exp. Med., 1986, 163(5), 1037-1050.
51. Siepl, C.; Bodmer, S.; Frei, K.; Macdonald, H.R.; De Martin, R.; Hofer, E.; Fontana, A. The glioblastoma-derived T cell suppressor factor/transforming growth factor-beta 2 inhibits T cell growth without affecting the interaction of interleukin 2 with its receptor. Eur. J. Immunol., 1988, 18(4), 593-600.
52. Thomas, D.A.; Massague, J. TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell, 2005, 8(5), 369-380.
53. Li, M.O.; Wan, Y.Y.; Sanjabi, S.; Robertson, A.K.; Flavell, R.A. Transforming growth factor-beta regulation of immune responses. Annu. Rev. Immunol., 2006, 24, 99-146.
54. Gabrilovich, D.I.; Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol., 2009, 9(3), 162-174.
55. El Andaloussi, A.; Lesniak, M.S. An increase in CD4+CD25+FOXP3+ regulatory T cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme. Neuro. Oncol., 2006, 8(3), 234-243.
56. Jacobs, J.F.; Idema, A.J.; Bol, K.F.; Nierkens, S.; Grauer, O.M.; Wesseling, P.; Grotenhuis, J.A.; Hoogerbrugge, P.M.; De Vries, I.J.; Adema, G.J. Regulatory T cells and the PD-L1/PD-1 pathway mediate immune suppression in malignant human brain tumors. Neuro. Oncol., 2009, 11(4), 394-402.
57. Heimberger, A.B.; Abou-Ghazal, M.; Reina-Ortiz, C.; Yang, D.S.; Sun, W.; Qiao, W.; Hiraoka, N.; Fuller, G.N. Incidence and prognostic impact of foxp3+ regulatory T cells in human gliomas. Clin. Cancer Res., 2008, 14(16), 5166-5172.
58. El Andaloussi, A.; Han, Y.; Lesniak, M.S. Prolongation of survival following depletion of CD4+CD25+ regulatory T cells in mice with experimental brain tumors. J. Neurosurg., 2006, 105(3), 430-437.
59. Grauer, O.M.; Sutmuller, R.P.; Van Maren, W.; Jacobs, J.F.; Bennink, E.; Toonen, L.W.; Nierkens, S.; Adema, G.J. Elimination of regulatory T cells is essential for an effective vaccination with tumor lysate-pulsed dendritic cells in a murine glioma model. Int. J. Cancer, 2008, 122(8), 1794-1802.
60. Biollaz, G.; Bernasconi, L.; Cretton, C.; Puntener, U.; Frei, K.; Fontana, A.; Suter, T. Site-specific anti-tumor immunity: differences in DC function, TGF-beta production and numbers of intratumoral Foxp3+ Treg. Eur. J. Immunol., 2009, 39(5), 1323-1333.
61. Wan, Y.Y.; Flavell, R.A. TGF-beta and regulatory T cell in immunity and autoimmunity. J. Clin. Immunol., 2008, 28(6),647-659.
62. Jachimczak, P.; Fabel-Schulte, K.; Hessdorfer, B.; Brysch, W.; Schlingensiepen, K.H.; Blesch, A.; Bogdahn, U. Transforming growth factor-beta-mediated regulation of human peripheral blood mononuclear cell proliferation as detected with phosphorothioate antisense oligodeoxynucleotides. Cell Immunol., 1995. 165(1), 125-133.
63. Hau, P.; Jachimczak, P.; Schlingensiepen, R.; Schulmeyer, F.; Jauch, T.; Steinbrecher, A.; Brawanski, A.; Proescholdt, M.; Schlaier, J.; Buchroithner, J.; Pichler, J.; Wurm, G.; Mehdorn, M.; Strege, R.; Schuierer, G.; Villarrubia, V.; Fellner, F.; Jansen, O.; Straube, T.; Nohria, V.; Goldbrunner, M.; Kunst, M.; Schmaus, S.; Stauder, G.; Bogdahn, U.; Schlingensiepen, K.H. Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies. Oligonucleotides, 2007, 17(2), 201-212.
64. Koochekpour, S.; Pilkington, G.J. Vascular and perivascular GD3 expression in human glioma. Cancer Lett., 1996, 104(1), 97-102.
65. Pertovaara, L.; Kaipainen, A.; Mustonen, T.; Orpana, A.; Ferrara, N.; Saksela, O.; Alitalo, K. Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. J. Biol. Chem., 1994, 269(9), 6271-6274.
66. Machein, M.R.; Plate, K.H. Role of VEGF in developmental angiogenesis and in tumor angiogenesis in the brain. Cancer Treat Res., 2004. 117, 191-218.
67. Stiles, J.D.; Ostrow, P.T.; Balos, L.L.; Greenberg, S.J.; Plunkett, R.; Grand, W.; Heffner, R.R. Jr. Correlation of endothelin-1 and transforming growth factor beta 1 with malignancy and vascularity in human gliomas. J. Neuropathol. Exp. Neurol., 1997. 56(4), 435-439.
68. Pepper, M.S. Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev., 1997. 8(1), 21-43.
69. Nygaard, S.J.; Haugland, H.K.; Laerum, O.D.; Lund-Johansen, M.; Bjerkvig, R.; Tysnes, O.B. Dynamic determination of human glioma invasion in vitro. J. Neurosurg., 1998. 89(3), 441-447.
70. Bhowmick, N.A.; Neilson, E.G.; Moses, H.L. Stromal fibroblasts in cancer initiation and progression. Nature, 2004. 432(7015), 332-337.
71. Kalluri, R.; Zeisberg, M. Fibroblasts in cancer. Nat. Rev. Cancer, 2006. 6(5), 392-401.
72. Pollard, J.W. Tumour-educated macrophages promote tumour progression and metastasis. Nat. Rev. Cancer, 2004. 4(1), 71-78.
73. Wels, J.; Kaplan, R.N.; Rafii, S.; Lyden, D. Migratory neighbors and distant invaders: tumor-associated niche cells. Genes. Dev., 2008. 22(5), 559-574.
74. Derynck, R.; Akhurst, R.J.; Balmain, A. TGF-beta signaling in tumor suppression and cancer progression. Nat. Genet., 2001. 29(2), 117-129.
75. Paulus, W.; Baur, I.; Huettner, C.; Schmausser, B.; Roggendorf, W.; Schlingensiepen, K.H.; Brysch, W. Effects of transforming growth factor-beta 1 on collagen synthesis, integrin expression, adhesion and invasion of glioma cells. J. Neuropathol. Exp. Neurol., 1995. 54(2), 236-244.
76. Arslan, F.; Bosserhoff, A.K.; Nickl-Jockschat, T.; Doerfelt, A.; Bogdahn, U.; Hau, P. The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-beta2. Br. J. Cancer, 2007, 96(10), 1560-1568.
77. Wesolowska, A.; Kwiatkowska, A.; Slomnicki, L.; Dembinski, M.; Master, A.; Sliwa, M.; Franciszkiewicz, K.; Chouaib, S.; Kaminska, B. Microglia-derived TGF-beta as an important regulator of glioblastoma invasion--an inhibition of TGF-betadependent effects by shRNA against human TGF-beta type II receptor. Oncogene, 2008, 27(7), 918-930.
78. Watabe, T.; Miyazono, K. Roles of TGF-beta family signaling in stem cell renewal and differentiation. Cell Res., 2009, 19(1), 103-115.
79. Penuelas, S.; Anido, J.; Prieto-Sanchez, R.M.; Folch, G.; Barba, I.; Cuartas, I.; Garcia-Dorado, D.; Poca, M.A.; Sahuquillo, J.; Baselga, J.; Seoane, J. TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma. Cancer Cell, 2009, 15(4), 315-327.
80. Ikushima, H.; Todo, T.; Ino, Y.; Takahashi, M.; Miyazawa, K.; Miyazono, K. Autocrine TGF-beta signaling maintains tumorigenicity of glioma-initiating cells through Sry-related HMGbox factors. Cell Stem Cell, 2009, 5(5), 504-514.
81. Seoane, J. TGFbeta and cancer initiating cells. Cell Cycle, 2009, 8(23), 3787-3788.
82. Dick, J.E. Stem cell concepts renew cancer research. Blood, 2008, 112(13), 4793-4807.
83. Marotta, L.L.; Polyak, K. Cancer stem cells: a model in the making. Curr. Opin. Genet. Dev., 2009, 19(1), 44-50.
84. Visvader, J.E.; Lindeman, G.J. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat. Rev. Cancer, 2008, 8(10), 755-768.
85. Singh, S.K.; Clarke, I.D.; Terasaki, M.; Bonn, V.E.; Hawkins, C.; Squire, J.; Dirks, P.B. Identification of a cancer stem cell in human brain tumors. Cancer Res., 2003, 63(18), 5821-5828.
86. Singh, S.K.; Clarke, I.D.; Hide, T.; Dirks, P.B. Cancer stem cells in nervous system tumors. Oncogene, 2004, 23(43), 7267-7273.
87. Beier, D.; Hau, P.; Proescholdt, M.; Lohmeier, A.; Wischhusen, J.; Oefner, P.J.; Aigner, L.; Brawanski, A.; Bogdahn, U.; Beier, C.P. CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res., 2007, 67(9), 4010-4015.
88. Phillips, H.S.; Kharbanda, S.; Chen, R.; Forrest, W.F.; Soriano, R.H.; Wu, T.D.; Misra, A.; Nigro, J.M.; Colman, H.; Soroceanu, L.; Williams, P.M.; Modrusan, Z.; Feuerstein, B.G.; Aldape, K. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell, 2006, 9(3), 157-173.
89. Wang, H.; Lathia, J.D.; Wu, Q.; Wang, J.; Li, Z.; Heddleston, J.M.; Eyler, C.E.; Elderbroom, J.; Gallagher, J.; Schuschu, J.; Macswords, J.; Cao, Y.; Mclendon, R.E.; Wang, X.F.; Hjelmeland, A.B.; Rich, J.N. Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth. Stem Cells, 2009, 27(10), 2393-2404.
90. Seoane, J. The TGFBeta pathway as a therapeutic target in cancer. Clin. Transl. Oncol., 2008, 10(1), 14-19.
91. Akhurst, R.J. Large-and small-molecule inhibitors of transforming growth factor-beta signaling. Curr. Opin. Investig. Drugs, 2006, 7(6), 513-521.
92. Dumont, N.; Arteaga, C.L. Targeting the TGF beta signaling network in human neoplasia. Cancer Cell, 2003, 3(6), 531-536.
93. Saunier, E.F.; Akhurst, R.J. TGF beta inhibition for cancer therapy. Curr. Cancer Drug Targets, 2006, 6(7), 565-578.
94. Wrzesinski, S.H.; Wan, Y.Y.; Flavell, R.A. Transforming growth factor-beta and the immune response: implications for anticancer therapy. Clin. Cancer Res., 2007, 13(18 Pt 1), 5262-5270.
95. Yingling, J.M.; Blanchard, K.L.; Sawyer, J.S. Development of TGF-beta signalling inhibitors for cancer therapy. Nat. Rev. Drug Discov., 2004. 3(12), 1011-1022.
96. Friese, M.A.; Wischhusen, J.; Wick, W.; Weiler, M.; Eisele, G.; Steinle, A.; Weller, M. RNA interference targeting transforming growth factor-beta enhances NKG2D-mediated antiglioma immune response, inhibits glioma cell migration and invasiveness, and abrogates tumorigenicity in vivo. Cancer Res., 2004. 64(20), 7596-603.
97. Schlingensiepen, K.H.; Schlingensiepen, R.; Steinbrecher, A.; Hau, P.; Bogdahn, U.; Fischer-Blass, B.; Jachimczak, P. Targeted tumor therapy with the TGF-beta2 antisense compound AP 12009. Cytokine Growth Factor Rev., 2006, 17(1-2), 129-139.
98. Jachimczak, P.; Fabel-Schulte, K.; Apfel, R.; Tschertner, I.; Schlingensiepen, K.-H.; Brysch, W.; Bogdahn, U. In: Evaluation of target sites for antisense oligodeoxynucleotides specific for transforming growth factor-beta1 and-beta2 mRNA gene walking. 89th Annual Meeting of the American Association for Cancer Research. 1998, Tulane.
99. Eckstein, F. Phosphorothioate analogues of nucleotides-Tools for the investigation of biochemical processes. Angewandte Chemie-International Edition in English, 1983, 22(6), 423-506.
100. Schlingensiepen, R.; Goldbrunner, M.; Szyrach, M.N.; Stauder, G.; Jachimczak, P.; Bogdahn, U.; Schulmeyer, F.; Hau, P.; Schlingensiepen, K.H. Intracerebral and intrathecal infusion of the TGF-beta 2-specific antisense phosphorothioate oligonucleotide AP 12009 in rabbits and primates: toxicology and safety. Oligonucleotides, 2005, 15(2), 94-104.
101. Bogdahn, U.; Hau, P.; Stockhammer, G.; Venkataramana, N.K.; Mahapatra, A.K.; Suri, A.; Balasubramaniam, A.; Nair, S.; Oliushine, V.; Parfenov, V.; Poverennova, I.; Zaaroor, M.; Jachimczak, P.; Ludwig, S.; Schmaus, S.; Heinrichs, H.; Schlingensiepen, K.H. Targeted therapy for high-grade glioma with the TGF-β2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. Neuro. Oncol., 2011, 13(1), 132-142.
102. Wolf, M.; Swaisland, H.; Averbuch, S. Development of the novel biologically targeted anticancer agent gefitinib: determining the optimum dose for clinical efficacy. Clin. Cancer Res., 2004, 10(14), 4607-4613.
103. Postel-Vinay, S.; Arkenau, H.T.; Olmos, D.; Ang, J.; Barriuso, J.; Ashley, S.; Banerji, U.; De-Bono, J.; Judson, I.; Kaye, S. Clinical benefit in Phase-I trials of novel molecularly targeted agents: does dose matter? Br. J. Cancer, 2009, 100(9), 1373-1378.
104. Jain, S.; Singhal, S.; Lee, P.; Xu, R. Molecular genetics of hepatocellular neoplasia. Am. J. Transl. Res., 2010, 2(1), 105-118.