TGF beta inhibition for cancer therapy

Current Cancer Drug Targets

Volumn 6, Issue 7, 2006, Pages 565-578

  Saunier, Elise F ^a   Akhurst, Rosemary J ^a,b,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Anti TGF therapy; Cancer; TGF ; TGF inhibition

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; AP 11014; AP 12009; BETAGLYCAN; BEVACIZUMAB; DECORIN; FETUIN; GC 1008; IMATINIB; LERDELIMUMAB; LY 2109761; LY 2157299; LY 364947; LY 550410; LY 580276; METELIMUMAB; PROTEIN INHIBITOR; SB 431542; SB 505124; SD 208; TEMOZOLOMIDE; TRANILAST; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA ANTIBODY; TRANSFORMING GROWTH FACTOR BETA INHIBITOR; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TRASTUZUMAB; TRX LEFL; TRX XFOXH1B; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANGIOGENESIS; BREAST CANCER; CANCER; CANCER GROWTH; CANCER THERAPY; CARCINOGENESIS; CELL SURFACE; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; COLORECTAL CANCER; DRUG DESIGN; DRUG EFFECT; DRUG INHIBITION; DRUG TARGETING; ENDOTHELIUM; FIBROBLAST; GENETIC VARIABILITY; GLIOMA; HUMAN; IMMUNE SYSTEM; LUNG NON SMALL CELL CANCER; MELANOMA; MICROENVIRONMENT; NONHUMAN; PANCREAS CARCINOMA; PERICYTE; PROGNOSIS; PROSTATE CANCER; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; THROMBOEMBOLISM; TUMOR CELL; VASCULAR DISEASE;

ANIMALS; ANTIBODIES, MONOCLONAL; DRUG DESIGN; HUMANS; NEOPLASMS; OLIGONUCLEOTIDES, ANTISENSE; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA;

EID: 33749235401     PISSN: 15680096     EISSN: None     Source Type: Journal    
DOI: 10.2174/156800906778742460     Document Type: Review

References (143)

1. Akhurst, R. J.; Derynck, R. TGF-beta signaling in cancer - a double-edged sword. Trends Cell Biol. 2001, 11, S44-S51.
2. Wakefield, L. M.; Roberts, A. B. TGF-beta signaling: positive and negative effects on tumorigenesis. Curr. Opin. Genet. Dev. 2002, 12, 22-29.
3. Siegel, P. M.; Massague, J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat. Rev. Cancer 2003, 3, 807-821.
4. Dumont, N.; Arteaga, C. L. Targeting the TGF beta signaling network in human neoplasia. Cancer Cell 2003, 3, 531-536.
5. Yingling, J. M.; Blanchard, K. L.; Sawyer, J. S. Development of TGF-beta signalling inhibitors for cancer therapy. Nat. Rev. Drug Discov. 2004, 3, 1011-1022.
6. Derynck, R.; Zhang, Y. E. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003, 425, 577-584.
7. Xu, L.; Kang, Y.; Col, S.; Massague, J. Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFbeta signaling complexes in the cytoplasm and nucleus. Mol. Cell 2002, 10, 271-282.
8. Datto, M.; Wang, X. F. Ubiquitin-mediated degradation a mechanism for fine-tuning TGF-beta signaling. Cell 2005, 121, 2-4.
9. Mishra, L.; Marshall, B. Adaptor proteins and ubiquinators in TGF-beta signaling. Cytokine Growth Factor Rev. 2006, 17, 75-87.
10. Hocevar, B. A.; Brown, T. L.; Howe, P. H. TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway. EMBO J. 1999, 18, 1345-1356.
11. Yu, L.; Hebert, M. C.; Zhang, Y. E. TGF-beta receptor-activated p38 MAP kinase mediates Smad-independent TGF-beta responses. EMBO J. 2002, 21, 3749-3759.
12. Shim, J. H.; Xiao, C.; Paschal, A. E.; Bailey, S. T.; Rao, P.; Hayden, M. S.; Lee, K. Y.; Bussey, C.; Steckel, M.; Tanaka, N.; Yamada, G.; Akira, S.; Matsumoto, K.; Ghosh, S. TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev. 2005, 19, 2668-2681.
13. Lu, T.; Burdelya, L. G.; Swiatkowski, S. M.; Boiko, A. D.; Howe, P. H.; Stark, G. R.; Gudkov, A. V. Secreted transforming growth factor beta2 activates NF-kappaB, blocks apoptosis, and is essential for the survival of some tumor cells. Proc. Natl. Acad. Sci. USA 2004, 101, 7112-7117.
14. Bhowmick, N. A.; Ghiassi, M.; Bakin, A.; Aakre, M.; Lundquist, C. A.; Engel, M. E.; Arteaga, C. L.; Moses, H. L. Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol. Biol. Cell 2001, 12, 27-36.
15. Edlund, S.; Landstrom, M.; Heldin, C. H.; Aspenstrom, P. Transforming growth factor-beta-induced mobilization of actin cytoskeleton requires signaling by small GTPases Cdc42 and RhoA. Mol. Biol. Cell 2002, 13, 902-914.
16. Bakin, A. V.; Tomlinson, A. K.; Bhowmick, N. A.; Moses, H. L.; Arteaga, C. L. Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration. J. Biol. Chem. 2000, 275, 36803-36810.
17. Vinals, F.; Pouyssegur, J. Transforming growth factor beta1 (TGF-beta1) promotes endothelial cell survival during in vitro angiogenesis via an autocrine mechanism implicating TGF-alpha signaling. Mol. Cell. Biol. 2001, 21, 7218-7230.
18. Yi, J. Y.; Shin, I.; Arteaga, C. L. Type I transforming growth factor beta receptor binds to and activates phosphatidylinositol 3-kinase. J. Biol. Chem. 2005, 280, 10870-10876.
19. Petritsch, C.; Beug, H.; Balmain, A.; Oft, M. TGF-beta inhibits p70 S6 kinase via protein phosphatase 2A to induce G(1) arrest. Genes Dev. 2000, 14, 3093-3101.
20. Moustakas, A.; Heldin, C. H. Non-Smad TGF-beta signals. J. Cell Sci. 2005, 118, 3573-3584.
21. de Caestecker, M. P.; Parks, W. T.; Frank, C. J.; Castagnino, P.; Bottaro, D. P.; Roberts, A. B.; Lechleider, R. J. Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases. Genes Dev. 1998, 12, 1587-1592.
22. Engel, M. E.; McDonnell, M. A.; Law, B. K.; Moses, H. L. Interdependent SMAD and JNK signaling in transforming growth factor-beta-mediated transcription. J. Biol. Chem. 1999, 274, 37413-37420.
23. Yakymovych, I.; Ten Dijke, P.; Heldin, C. H.; Souchelnytskyi, S. Regulation of Smad signaling by protein kinase C. FASEB J. 2001, 15, 553-555.
24. Brown, J. D.; DiChiara, M. R.; Anderson, K. R.; Gimbrone, M. A., Jr.; Topper, J. N. MEKK-1, a component of the stress (stress-activated protein kinase/c-Jun N-terminal kinase) pathway, can selectively activate Smad2-mediated transcriptional activation in endothelial cells. J. Biol. Chem. 1999, 274, 8797-8805.
25. Wicks, S. J.; Lui, S.; Abdel-Wahab, N.; Mason, R. M.; Chantry, A. Inactivation of smad-transforming growth factor beta signaling by Ca(2+)-calmodulin-dependent protein kinase II. Mol. Cell. Biol. 2000, 20, 8103-8111.
26. Deininger, M.; Buchdunger, E.; Druker, B. J. The development of Imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005, 105, 2640-2653.
27. Arteaga, C. L.; Moulder, S. L.; Yakes, F. M. HER (erbB) tyrosine kinase inhibitors in the treatment of breast cancer. Semin. Oncol. 2002, 29, 4-10.
28. Ferrara, N. VEGF as a therapeutic target in cancer. Oncology 2005, 69(Suppl 3), 11-16.
29. Cui, W.; Fowlis, D. J.; Bryson, S.; Duffie, E.; Ireland, H.; Balmain, A.; Akhurst, R. J. TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 1996, 86, 531-542.
30. Han, G.; Lu, S. L.; Li, A. G.; He, W.; Corless, C. L.; Kulesz-Martin, M.; Wang, X. J. Distinct mechanisms of TGF-beta1-mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis. J. Clin. Invest. 2005, 115(7), 1714-1723.
31. Muraoka, R. S.; Koh, Y.; Roebuck, L. R.; Sanders, M. E.; Brantley-Sieders, D.; Gorska, A. E.; Moses, H. L.; Arteaga, C. L. Increased malignancy of Neu-induced mammary tumors overexpressing active transforming growth factor beta1. Mol. Cell. Biol. 2003, 23, 8691-8703.
32. Oft, M.; Heider, K. H.; Beug, H. TGFbeta signaling is necessary for carcinoma cell invasiveness and metastasis. Curr. Biol. 1998, 8, 1243-1252.
33. Portella, G.; Cumming, S. A.; Liddell, J.; Cui, W.; Ireland, H.; Akhurst, R. J.; Balmain, A. Transforming growth factor beta is essential for spindle cell conversion of mouse skin carcinoma in vivo: implications for tumor invasion. Cell Growth Differ. 1998, 9, 393-404.
34. Yin, J. J.; Selander, K.; Chirgwin, J. M.; Dallas, M.; Grubbs, B. G.; Wieser, R.; Massague, J.; Mundy, G. R.; Guise, T. A. TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J. Clin. Invest. 1999, 103, 197-206.
35. Oft, M.; Akhurst, R. J.; Balmain, A. Metastasis is driven by sequential elevation of H-ras and Smad2 levels. Nat. Cell Biol. 2002, 4, 487-494.
36. Tian, F.; Byfield, S. D.; Parks, W. T.; Stuelten, C. H.; Nemani, D.; Zhang, Y. E.; Roberts, A. B. Smad-binding defective mutant of transforming growth factor beta type I receptor enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. Cancer Res. 2004, 64, 4523-4530.
37. Muraoka-Cook, R. S.; Shin, I.; Yi, J. Y.; Easterly, E.; Barcellos-Hoff, M. H.; Yingling, J. M.; Zent, R.; Arteaga, C. L. Activated type I TGFbeta receptor kinase enhances the survival of mammary epithelial cells and accelerates tumor progression. Oncogene 2006, 25, 3408-3423.
38. Pulyaeva, H.; Bueno, J.; Polette, M.; Birembaut, P.; Sato, H.; Seiki, M.; Thompson, E. W. MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells. Clin. Exp. Metastasis 1997, 15, 111-120.
39. Tester, A. M.; Ruangpanit, N.; Anderson, R. L.; Thompson, E. W. MMP-9 secretion and MMP-2 activation distinguish invasive and metastatic sublines of a mouse mammary carcinoma system showing epithelial-mesenchymal transition traits. Clin. Exp. Metastasis 2000, 18, 553-560.
40. Akhurst, R. J. TGFb signaling in epithelial/mesenchymal transition and invasion/metastasis. in TGFbeta, Derynck, R. and Miyazono, K., Editors. CSHL. 2006, in press.
41. Oft, M.; Peli, J.; Rudaz, C.; Schwarz, H.; Beug, H.; Reichmann, E. TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev. 1996, 10, 2462-2477.
42. Kang, Y.; Siegel, P. M.; Shu, W.; Drobnjak, M.; Kakonen, S. M.; Cordon-Cardo, C.; Guise, T. A.; Massague, J. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003, 3, 537-549.
43. Derynck, R.; Akhurst, R. J.; Balmain, A. TGF-beta signaling in tumor suppression and cancer progression. Nat. Genet. 2001, 29, 117-129.
44. Bhowmick, N. A.; Chytil, A.; Plieth, D.; Govska, A. E.; Dumont, N.; Shappell, S.; Washington, M. K.; Neilson, E. G.; Moses, H. L. TGFbeta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelial. Science 2004, 303, 848-851.
45. Mishra, L.; Derynck, R.; Mishra, B. Transforming growth factor-beta signaling in stem cells and cancer. Science 2005, 310, 68-71.
46. Letterio, J. J. Murine models define the role of TGF-beta as a master regulator of immune cell function. Cytokine Growth Factor Rev. 2000, 11, 81-87.
47. Gorelik, L.; Flavell, R. A. Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat. Med. 2001, 7, 1118-1122.
48. Gorelik, L.; Flavell, R. A. Transforming growth factor-beta in Tcell biology. Nat. Rev. Immunol. 2002, 2, 46-53.
49. Nakagawa, T.; Li, J. H.; Garcia, G.; Mu, W.; Piek, E.; Bottinger, E. P.; Chen, Y.; Zhu, H. J.; Kang, D. H.; Schreiner, G. F.; Lan, H. Y.; Johnson, R. J. TGF-beta induces proangiogenic and antiangiogenic factors via parallel but distinct Smad pathways. Kidney Int. 2004, 66, 605-613.
50. Shirai, Y.; Kawata, S.; Ito, N.; Tamura, S.; Takaishi, K.; Kiso, S.; Tsushima, H.; Matsuzawa, Y. Elevated levels of plasma transforming growth factor-beta in patients with hepatocellular carcinoma. Jpn. J. Cancer Res. 1992, 83, 676-679.
51. Ito, N.; Kawata, S.; Tamura, S.; Shirai, Y.; Kiso, S.; Tsushima, H.; Matsuzawa, Y. Positive correlation of plasma transforming growth factor-beta 1 levels with tumor vascularity in hepatocellular carcinoma. Cancer Lett. 1995, 89, 45-48.
52. Tsushima, H.; Kawata, S.; Tamura, S.; Ito, N.; Shirai, Y.; Kiso, S.; Imai, Y.; Shimomukai, H.; Nomura, Y.; Matsuda, Y.; Matsuzawa, Y. High levels of transforming growth factor beta 1 in patients with colorectal cancer: association with disease progression. Gastroenterology 1996, 110, 375-382.
53. Ito, N.; Kawata, S.; Tsushima, H.; Tamura, S.; Kiso, S.; Takami, S.; Igura, T.; Monnden, M.; Matsuzawa, Y. Increased circulating transforming growth factor beta1 in a patient with giant hepatic hemangioma: possible contribution to an impaired immune function. Hepatology 1997, 25, 93-96.
54. 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, 1258-1262.
55. Shariat, S. F.; Kattan, M. W.; Traxel, E.; Andrews, B.; Zhu, K.; Wheeler, T. M.; Slawin, K. M. Association of pre- and postoperative plasma levels of transforming growth factor beta(1) and interleukin 6 and its soluble receptor with prostate cancer progression. Clin. Cancer Res. 2004, 10, 1992-1999.
56. Barthelemy-Brichant, N.; David, J. L.; Bosquee, L.; Bury, T.; Seidel, L.; Albert, A.; Bartsch, P.; Baugnet-Mahieu, L.; Deneufbourg, J. M. Increased TGFbeta1 plasma level in patients with lung cancer: potential mechanisms. Eur. J. Clin. Invest. 2002, 32, 193-198.
57. Huang, A.; Gilmour, J. W.; Imami, N.; Amjadi, P.; Henderson, D. C.; Allen-Mersh, T. G. Increased serum transforming growth factor-beta1 in human colorectal cancer correlates with reduced circulating dendritic cells and increased colonic Langerhans cell infiltration. Clin. Exp. Immunol. 2003, 134, 270-278.
58. Harada, M.; Tatsugami, K.; Nomoto, M.; Nomoto, K. Circulating immunoglobulin-bound transforming growth factor beta at a late tumour-bearing stage impairs antigen-specific responses of CD4+ T cells. Clin. Exp. Immunol. 2002, 128, 204-212.
59. Bassi, D. E.; Fu, J.; Lopez de Cicco, R.; Klein-Szanto, A. J. Proprotein convertases: "master switches" in the regulation of tumor growth and progression. Mol. Carcinog. 2005, 44, 151-161.
60. Bassi, D. E.; Mahloogi, H.; Lopez De Cicco, R.; Klein-Szanto, A. Increased furin activity enhances the malignant phenotype of human head and neck cancer cells. Am. J. Pathol. 2003, 162, 439-447.
61. Dubois, C. M.; Blanchette, F.; Laprise, M. H.; Leduc, R.; Grondin, F.; Seidah, N. G. Evidence that furin is an authentic transforming growth factor-beta1-converting enzyme. Am. J. Pathol. 2001, 158, 305-316.
62. Leitlein, J.; Aulwurm, S.; Waltereit, R.; Naumann, U.; Wagenknecht, B.; Garten, W.; Weller, M.; Platten, M. Processing of immunosuppressive pro-TGF-beta 1,2 by human glioblastoma cells involves cytoplasmic and secreted furin-like proteases. J. Immunol. 2001, 166, 7238-7243.
63. Platten, M.; Wild-Bode, C.; Wick, W.; Leitlein, J.; Dichgans, J.; Weller, M. N-[3,4-dimethoxycinnamoyl]-anthranilic acid (tranilast) inhibits transforming growth factor-beta relesase and reduces migration and invasiveness of human malignant glioma cells. Int. J. Cancer 2001, 93, 53-61.
64. Yamaguchi, Y.; Mann, D. M.; Ruoslahti, E. Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature 1990, 346, 281-284.
65. Border, W. A.; Noble, N. A.; Yamamoto, T.; Harper, J. R.; Yamaguchi, Y.; Pierschbacher, M. D.; Ruoslahti, E. Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease. Nature 1992, 360, 361-364.
66. Isaka, Y.; Brees, D. K.; Ikegaya, K.; Kaneda, Y.; Imai, E.; Noble, N. A.; Border, W. A. Gene therapy by skeletal muscle expression of decorin prevents fibrotic disease in rat kidney. Nat. Med. 1996, 2, 418-423.
67. Stander, M.; Naumann, U.; Dumitrescu, L.; Heneka, M.; Loschmann, P.; Gulbins, E.; Dichgans, J.; Weller, M. Decorin gene transfer-mediated suppression of TGF-beta synthesis abrogates experimental malignant glioma growth in vivo. Gene Ther. 1998, 5, 1187-1194.
68. Comalada, M.; Cardo, M.; Xaus, J.; Valledor, A. F.; Lloberas, J.; Ventura, F.; Celada, A. Decorin reverses the repressive effect of autocrine-produced TGF-beta on mouse macrophage activation. J. Immunol. 2003, 170, 4450-4456.
69. Reed, C. C.; Gauldie, J.; Iozzo, R. V. Suppression of tumorigenicity by adenovirus-mediated gene transfer of decorin. Oncogene 2002, 21, 3688-3695.
70. Reed, C. C.; Waterhouse, A.; Kirby, S.; Kay, P.; Owens, R. T.; McQuillan, D. J.; Iozzo, R. V. Decorin prevents metastatic spreading of breast cancer. Oncogene 2005, 24, 1104-1110.
71. Demetriou, M.; Binkert, C.; Sukhu, B.; Tenenbaum, H. C.; Dennis, J. W. Fetuin/alpha2-HS glycoprotein is a transforming growth factor-beta type II receptor mimic and cytokine antagonist. J. Biol. Chem. 1996, 271, 12755-12761.
72. Vilchis-Landeros, M. M.; Montiel, J. L.; Mendoza, V.; Mendoza-Hernandez, G.; Lopez-Casillas, F. Recombinant soluble betaglycan is a potent and isoform-selective transforming growth factor-beta neutralizing agent. Biochem. J. 2001, 355, 215-222.
73. Bandyopadhyay, A.; Lopez-Casillas, F.; Malik, S. N.; Montiel, J. L.; Mendoza, V.; Yang, J.; Sun, L. Z. Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft. Cancer Res. 2002, 62, 4690-4695.
74. Bandyopadhyay, A.; Wang, L.; Lopez-Casillas, F.; Mendoza, V.; Yeh, I. T.; Sun, L. Systemic administration of a soluble betaglycan suppresses tumor growth, angiogenesis, and matrix metalloproteinase-9 expression in a human xenograft model of prostate cancer. Prostate 2005, 63, 81-90.
75. Yang, Y. A.; Dukhanina, O.; Tang, B.; Mamura, M.; Letterio, J. J.; MacGregor, J.; Patel, S. C.; Khozin, S.; Liu, Z. Y.; Green, J.; Anver, M. R.; Merlino, G.; Wakefield, L. M. Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. J. Clin. Invest. 2002, 109, 1607-1615.
76. Rowland-Goldsmith, M. A.; Maruyama, H.; Kusama, T.; Ralli, S.; Korc, M. Soluble type II transforming growth factor-beta (TGF-beta) receptor inhibits TGF-beta signaling in COLO-357 pancreatic cancer cells in vitro and attenuates tumor formation. Clin. Cancer Res. 2001, 7, 2931-2940.
77. Rowland-Goldsmith, M. A.; Maruyama, H.; Matsuda, K.; Idezawa, T.; Ralli, M.; Ralli, S.; Korc, M. Soluble type II transforming growth factor-beta receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis. Mol. Cancer Ther. 2002, 1, 161-167.
78. Suzuki, E.; Kapoor, V.; Cheung, H. K.; Ling, L. E.; DeLong, P. A.; Kaiser, L. R.; Albelda, S. M. Soluble type II transforming growth factor-beta receptor inhibits established murine malignant mesothelioma tumor growth by augmenting host antitumor immunity. Clin. Cancer Res. 2004, 10, 5907-5918.
79. Rabbani, Z. N.; Anscher, M. S.; Zhang, X.; Chen, L.; Samulski, T. V.; Li, C. Y.; Vujaskovic, Z. Soluble TGFbeta type II receptor gene therapy ameliorates acute radiation-induced pulmonary injury in rats. Int. J. Radiat. Oncol. Biol. Phys. 2003, 57, 563-572.
80. Kontani, K.; Kajino, K.; Huangi, C. L.; Fujino, S.; Taguchi, O.; Yamauchi, A.; Yokomise, H.; Ogasawara, K. Spontaneous elicitation of potent antitumor immunity and eradication of established tumors by administration of DNA encoding soluble transforming growth factor-beta II receptor without active antigen-sensitization. Cancer Immunol. Immunother. 2006, 55, 579-587.
81. Ezquerro, I. J.; Lasarte, J. J.; Dotor, J.; Castilla-Cortazar, I.; Bustos, M.; Penuelas, I.; Blanco, G.; Rodriguez, C.; Lechuga Mdel, C.; Greenwel, P.; Rojkind, M.; Prieto, J.; Borras-Cuesta, F. A synthetic peptide from transforming growth factor beta type III receptor inhibits liver fibrogenesis in rats with carbon tetrachloride liver injury. Cytokine 2003, 22, 12-20.
82. Santiago, B.; Gutierrez-Canas, I.; Dotor, J.; Palao, G.; Lasarte, J. J.; Ruiz, J.; Prieto, J.; Borras-Cuesta, F.; Pablos, J. L. Topical application of a peptide inhibitor of transforming growth factor-beta1 ameliorates bleomycin-induced skin fibrosis. J. Invest. Dermatol. 2005, 125, 450-455.
83. Mead, A. L.; Wong, T. T.; Cordeiro, M. F.; Anderson, I. K.; Khaw, P. T. Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery. Invest. Ophthalmol. Vis. Sci. 2003, 44, 3394-3401.
84. Fakhrai, H.; Dorigo, O.; Shawler, D. L.; Lin, H.; Mercola, D.; Black, K. L.; Royston, I.; Sobol, R. E. Eradication of established intracranial rat gliomas by transforming growth factor beta antisense gene therapy. Proc. Natl. Acad. Sci. USA 1996, 93, 2909-2914.
85. Liau, L. M.; Fakhrai, H.; Black, K. L. Prolonged survival of rats with intracranial C6 gliomas by treatment with TGF-beta antisense gene. Neurol. Res. 1998, 20, 742-747.
86. 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, 129-139.
87. 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-beta2-specific antisense phosphorothioate oligonucleotide AP 12009 in rabbits and primates: Toxicology and Safety. Oligonucleotides 2005, 15, 94-104.
88. Isaka, Y.; Nakamura, H.; Mizui, M.; Takabatake, Y.; Horio, M.; Kawachi, H.; Shimizu, F.; Imai, E.; Hori, M. DNAzyme for TGF-beta suppressed extracellular matrix accumulation in experimental glomerulonephritis. Kidney Int. 2004, 66, 586-590.
89. Inman, G. J.; Nicolas, F. J.; Callahan, J. F.; Harling, J. D.; Gaster, L. M.; Reith, A. D.; Laping, N. J.; Hill, C. S. SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol. Pharmacol. 2002, 62, 65-74.
90. Sawyer, J. S.; Anderson, B. D.; Beight, D. W.; Campbell, R. M.; Jones, M. L.; Herron, D. K.; Lampe, J. W.; McCowan, J. R.; McMillen, W. T.; Mort, N.; Parsons, S.; Smith, E. C.; Vieth, M.; Weir, L. C.; Yan, L.; Zhang, F.; Yingling, J. M. Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain. J. Med. Chem. 2003, 46, 3953-3956.
91. Singh, J.; Chuaqui, C. E.; Boriack-Sjodin, P. A.; Lee, W. C.; Pontz, T.; Corbley, M. J.; Cheung, H. K.; Arduini, R. M.; Mead, J. N.; Newman, M. N.; Papadatos, J. L.; Bowes, S.; Josiah, S.; Ling, L. E. Successful shape-based virtual screening: the discovery of a potent inhibitor of the type I TGFbeta receptor kinase (TbetaRI). Bioorg. Med. Chem. Lett. 2003, 13, 4355-4359.
92. Hayashi, T.; Hideshima, T.; Nguyen, A. N.; Munoz, O.; Podar, K.; Hamasaki, M.; Ishitsuka, K.; Yasui, H.; Richardson, P.; Chakravarty, S.; Murphy, A.; Chauhan, D.; Higgins, L. S.; Anderson, K. C. Transforming growth factor beta receptor I kinase inhibitor down-regulates cytokine secretion and multiple myeloma cell growth in the bone marrow microenvironment. Clin. Cancer Res. 2004, 10, 7540-7546.
93. Uhl, M.; Aulwurm, S.; Wischhusen, J.; Weiler, M.; Ma, J. Y.; Almirez, R.; Mangadu, R.; Liu, Y. W.; Platten, M.; Herrlinger, U.; Murphy, A.; Wong, D. H.; Wick, W.; Higgins, L. S.; Weller, M. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res. 2004, 64, 7954-7961.
94. Singh, J.; Ling, L. E.; Sawyer, J. S.; Lee, W. C.; Zhang, F.; Yingling, J. M. Transforming the TGFbeta pathway: convergence of distinct lead generation strategies on a novel kinase pharmacophore for TbetaRI (ALK5). Curr. Opin. Drug Discov. Devel. 2004, 7, 437-445.
95. Cui, Q.; Lim, S. K.; Zhao, B.; Hoffmann, F. M. Selective inhibition of TGF-beta responsive genes by Smad-interacting peptide aptamers from FoxH1, Lef1 and CBP. Oncogene 2005, 24, 3864-3874.
96. Seton-Rogers, S. E.; Lu, Y.; Hines, L. M.; Koundinya, M.; LaBaer, J.; Muthuswamy, S. K.; Brugge, J. S. Cooperation of the ErbB2 receptor and transforming growth factor beta in induction of migration and invasion in mammary epithelial cells. Proc. Natl. Acad. Sci. USA 2004, 101, 1257-1262.
97. Bonyadi, M.; Rusholme, S. A.; Cousins, F. M.; Su, H. C.; Biron, C. A.; Farrall, M.; Akhurst, R. J. Mapping of a major genetic modifier of embryonic lethality in TGF beta 1 knockout mice. Nat. Genet. 1997, 15, 207-211.
98. Tang, Y.; McKinnon, M. L.; Leong, L. M.; Rusholme, S. A.; Wang, S.; Akhurst, R. J. Genetic modifiers interact with maternal determinants in vascular development of Tgfb1(-/-) mice. Hum. Mol. Genet. 2003, 12, 1579-1589.
99. Tang, Y.; Sook Lee, K.; Yang, H.; Logan, D. W.; Wang, S.; McKinnon, M. L.; Holt, L. J.; Condie, A.; Luu, M. T.; Akhurst, R. J. Epistatic interactions between modifier genes confer strain-specific redundancy for Tgfb1 in developmental angiogenesis. Genomics 2005, 85, 60-70.
100. Cambien, F.; Ricard, S.; Troesch, A.; Mallet, C.; Generenaz, L.; Evans, A.; Arveiler, D.; Luc, G.; Ruidavets, J. B.; Poirier, O. Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure. The Etude Cas-Temoin de l'Infarctus du Myocarde (ECTIM) Study. Hypertension 1996, 28, 881-887.
101. Chen, T.; Triplett, J.; Dehner, B.; Hurst, B.; Colligan, B.; Pemberton, J.; Graff, J. R.; Carter, J. H. Transforming growth factor-beta receptor type I gene is frequently mutated in ovarian carcinomas. Cancer Res. 2001, 61, 4679-4682.
102. Pasche, B.; Kolachana, P.; Nafa, K.; Satagopan, J.; Chen, Y. G.; Lo, R. S.; Brener, D.; Yang, D.; Kirstein, L.; Oddoux, C.; Ostrer, H.; Vineis, P.; Varesco, L.; Jhanwar, S.; Luzzatto, L.; Massague, J.; Offit, K. TbetaR-I(6A) is a candidate tumor susceptibility allele. Cancer Res. 1999, 59, 5678-5682.
103. Zhang, H. T.; Zhao, J.; Zheng, S. Y.; Chen, X. F. Is TGFBR1*6A really associated with increased risk of cancer? J. Clin. Oncol. 2005, 23, 7743-7744; author reply 7744-7746.
104. Dunning, A. M.; Ellis, P. D.; McBride, S.; Kirschenlohr, H. L.; Healey, C. S.; Kemp, P. R.; Luben, R. N.; Chang-Claude, J.; Mannermaa, A.; Kataja, V.; Pharoah, P. D.; Easton, D. F.; Ponder, B. A.; Metcalfe, J. C. A transforming growth factorbeta1 signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer. Cancer Res. 2003, 63, 2610-2615.
105. Ewart-Toland, A.; Chan, J. M.; Yuan, J.; Balmain, A.; Ma, J. A gain of function TGFB1 polymorphism may be associated with late stage prostate cancer. Cancer Epidemiol. Biomarkers Prev. 2004, 13, 759-764.
106. Ziv, E.; Cauley, J.; Morin, P. A.; Saiz, R.; Browner, W. S. Association between the T29→C polymorphism in the transforming growth factor beta1 gene and breast cancer among elderly white women: The Study of Osteoporotic Fractures. JAMA 2001, 285, 2859-2863.
107. Hishida, A.; Iwata, H.; Hamajima, N.; Matsuo, K.; Mizutani, M.; Iwase, T.; Miura, S.; Emi, N.; Hirose, K.; Tajima, K. Transforming Growth Factor B1 T29C Polymorphism and Breast Cancer Risk in Japanese Women. Breast Cancer 2003, 10, 63-69.
108. Yamada, Y.; Fujisawa, M.; Ando, F.; Niino, N.; Tanaka, M.; Shimokata, H. Association of a polymorphism of the transforming growth factor-beta1 gene with blood pressure in Japanese individuals. J. Hum. Genet. 2002, 47, 243-248.
109. Yokota, M.; Ichihara, S.; Lin, T. L.; Nakashima, N.; Yamada, Y. Association of a T29→C polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to myocardial infarction in Japanese. Circulation 2000, 101, 2783-2787.
110. Grainger, D. J.; Heathcote, K.; Chiano, M.; Snieder, H.; Kemp, P. R.; Metcalfe, J. C.; Carter, N. D.; Spector, T. D. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum. Mol. Genet. 1999, 8, 93-97.
111. Shin, A.; Shu, X. O.; Cai, Q.; Gao, Y. T.; Zheng, W. Genetic polymorphisms of the transforming growth factor-beta1 gene and breast cancer risk: a possible dual role at different cancer stages. Cancer Epidemiol. Biomarkers Prev. 2005, 14, 1567-1570.
112. Kaklamani, V. G.; Baddi, L.; Liu, J.; Rosman, D.; Phukan, S.; Bradley, C.; Hegarty, C.; McDaniel, B.; Rademaker, A.; Oddoux, C.; Ostrer, H.; Michel, L. S.; Huang, H.; Chen, Y.; Ahsan, H.; Offit, K.; Pasche, B. Combined genetic assessment of transforming growth factor-beta signaling pathway variants may predict breast cancer risk. Cancer Res. 2005, 65, 3454-3461.
113. Pasche, B.; Kaklamani, V.; Hou, N.; Young, T.; Rademaker, A.; Peterlongo, P.; Ellis, N.; Offit, K.; Caldes, T.; Reiss, M.; Zheng, T. TGFBR1*6A and cancer: a meta-analysis of 12 case-control studies. J. Clin. Oncol. 2004, 22, 756-758.
114. Zhang, H. T. Int7G24A variant of the TGFBR1 gene and cancer risk: a meta-analysis of three case-control studies. Lung Cancer 2005, 49, 419-420.
115. Mao, J. H.; Saunier, E. F.; de Koning, J. P.; McKinnon, M. M.; Higgins, M. N.; Nicklas, K.; Yang, H. T.; Balmain, A.; Akhurst, R. J. Genetic variants of Tgfb1 act as context-dependent modifiers of mouse skin tumor susceptibility. Proc. Natl. Acad. Sci. USA 2006, 103, 8125-8130.
116. Arteaga, C. L. Selecting the right patient for tumor therapy. Nat. Med. 2004, 10, 577-578.
117. Fan, Q. W.; Knight, Z. A.; Goldenberg, D. D.; Yu, W.; Mostov, K. E.; Stokoe, D.; Shokat, K. M.; Weiss, W. A. A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. Cancer Cell 2006, 9, 341-349.
118. Frantz, S. Drug discovery: playing dirty. Nature 2005, 437, 942-943.
119. Roberts, R. B.; Arteaga, C. L.; Threadgill, D. W. Modeling the cancer patient with genetically engineered mice: prediction of toxicity from molecule-targeted therapies. Cancer Cell 2004, 5, 115-120.
120. Mizuguchi, T.; Collod-Beroud, G.; Akiyama, T.; Abifadel, M.; Harada, N.; Morisaki, T.; Allard; Varret, M.; Claustres, M.; Morisaki, H.; Ihara, M.; Kinoshita, A.; Yoshiura, K.-i.; Junien, C.; Kajii, T.; Jondeau, G.; Ohta, T.; Kishino, T.; Furukawa, Y.; Nakamura, Y.; Niikawa, N.; Boileau, C.; Matsumoto, N. Heterozygous TGFBR2 mutation in Marfan syndrome. Nat. Genet. 2004, 36, 855-860.
121. Loeys, B. L.; Chen, J.; Neptune, E. R.; Judge, D. P.; Podowski, M.; Holm, T.; Meyers, J.; Leitch, C. C.; Katsanis, N.; Sharifi, N.; Xu, F. L.; Myers, L. A.; Spevak, P. J.; Cameron, D. E.; De Backer, J.; Hellemans, J.; Chen, Y.; Davis, E. C.; Webb, C. L.; Kress, W.; Coucke, P.; Rifkin, D. B.; De Paepe, A. M.; Dietz, H. C. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat. Genet. 2005, 37, 275-281.
122. Pannu, H.; Fadulu, V. T.; Chang, J.; Lafont, A.; Hasham, S. N.; Sparks, E.; Giampietro, P. F.; Zaleski, C.; Estrera, A. L.; Safi, H. J.; Shete, S.; Willing, M. C.; Raman, C. S.; Milewicz, D. M. Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections. Circulation 2005, 112, 513-520.
123. Lebrin, F.; Goumans, M. J.; Jonker, L.; Carvalho, R. L.; Valdimarsdottir, G.; Thorikay, M.; Mummery, C.; Arthur, H. M.; ten Dijke, P. Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction. EMBO J. 2004, 23, 4018-4028.
124. Shah, M. A.; Ilson, D.; Kelsen, D. P. Thromboembolic events in gastric cancer: high incidence in patients receiving irinotecan- and bevacizumab-based therapy. J. Clin. Oncol. 2005, 23, 2574-2576.
125. Sanborn, R. E.; Sandler, A. B. The safety of bevacizumab. Expert Opin. Drug Saf. 2006, 5, 289-301.
126. Ferrara, N.; Kerbel, R. S. Angiogenesis as a therapeutic target. Nature 2005, 438, 967-974.
127. Hurwitz, H.; Fehrenbacher, L.; Novotny, W.; Cartwright, T.; Hainsworth, J.; Heim, W.; Berlin, J.; Baron, A.; Griffing, S.; Holmgren, E.; Ferrara, N.; Fyfe, G.; Rogers, B.; Ross, R.; Kabbinavar, F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 2004, 350, 2335-2342.
128. Kulkarni, A. B.; Huh, C. G.; Becker, D.; Geiser, A.; Lyght, M.; Flanders, K. C.; Roberts, A. B.; Sporn, M. B.; Ward, J. M.; Karlsson, S. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl. Acad. Sci. USA 1993, 90, 770-774.
129. Diebold, R. J.; Eis, M. J.; Yin, M.; Ormsby, I.; Boivin, G. P.; Darrow, B. J.; Saffitz, J. E.; Doetschman, T. Early-onset multifocal inflammation in the transforming growth factor beta 1-null mouse is lymphocyte mediated. Proc. Natl. Acad. Sci. USA 1995, 92, 12215-12219.
130. Akhurst, R. J. TGF beta signaling in health and disease. Nat. Genet. 2004, 36, 790-792.
131. Salnikov, A. V.; Roswall, P.; Sundberg, C.; Gardner, H.; Heldin, N. E.; Rubin, K. Inhibition of TGF-beta modulates macrophages and vessel maturation in parallel to a lowering of interstitial fluid pressure in experimental carcinoma. Lab. Invest. 2005, 85, 512-521.
132. Lacher, M. D.; Tiirikainen, M. I.; Saunier, E. F.; Christian, C.; Anders, M.; Oft, M.; Balmain, A.; Akhurst, R. J.; Korn, W. M. Transforming growth factor-beta receptor inhibition enhances adenoviral infectability of carcinoma cells via up-regulation of Coxsackie and Adenovirus Receptor in conjunction with reversal of epithelial-mesenchymal transition. Cancer Res. 2006, 66, 1648-1657.
133. O'Shea, C. C. Viruses - seeking and destroying the tumor program. Oncogene 2005, 24, 7640-7655.
134. Stockfleth, E.; Ulrich, C.; Meyer, T.; Christophers, E. Epithelial malignancies in organ transplant patients: clinical presentation and new methods of treatment. Recent Results Cancer Res. 2002, 160, 251-258.
135. Winkelhorst, J. T.; Brokelman, W. J.; Tiggeler, R. G.; Wobbes, T. Incidence and clinical course of de-novo malignancies in renal allograft recipients. Eur. J. Surg. Oncol. 2001, 27, 409-413.
136. Harden, P. N.; Fryer, A. A.; Reece, S.; Smith, A. G.; Ramsay, H. M. Annual incidence and predicted risk of nonmelanoma skin cancer in renal transplant recipients. Transplant Proc. 2001, 33, 1302-1304.
137. Bavinck, J. N.; De Boer, A.; Vermeer, B. J.; Hartevelt, M. M.; van der Woude, F. J.; Claas, F. H.; Wolterbeek, R.; Vandenbroucke, J. P. Sunlight, keratotic skin lesions and skin cancer in renal transplant recipients. Br. J. Dermatol. 1993, 129, 242-249.
138. Hojo, M.; Morimoto, T.; Maluccio, M.; Asano, T.; Morimoto, K.; Lagman, M.; Shimbo, T.; Suthanthiran, M. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 1999, 397, 530-534.
139. Luan, F. L.; Hojo, M.; Maluccio, M.; Yamaji, K.; Suthanthiran, M. Rapamycin blocks tumor progression: unlinking immunosuppression from antitumor efficacy. Transplantation 2002, 73, 1565-1572.
140. Guba, M.; von Breitenbuch, P.; Steinbauer, M.; Koehl, G.; Flegel, S.; Hornung, M.; Bruns, C. J.; Zuelke, C.; Farkas, S.; Anthuber, M.; Jauch, K. W.; Geissler, E. K. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat. Med. 2002, 8, 128-135.
141. Tanaka, T.; Takahara, S.; Hatori, M.; Suzuki, K.; Wang, J.; Ichimaru, N.; Suzuki, S.; Morozumi, K.; Okuyama, A.; Yamanaka, H. A novel immunosuppressive drug, FTY720, prevents the cancer progression induced by cyclosporine. Cancer Lett. 2002, 181, 165-171.
142. Khanna, A. K.; Plummer, M. S.; Hilton, G.; Pieper, G. M.; Ledbetter, S. Anti-transforming growth factor antibody at low but not high doses limits cyclosporine-mediated nephrotoxicity without altering rat cardiac allograft survival: potential of therapeutic applications. Circulation 2004, 110, 3822-3829.
143. Benigni, A.; Zoja, C.; Corna, D.; Zatelli, C.; Conti, S.; Campana, M.; Gagliardini, E.; Rottoli, D.; Zanchi, C.; Abbate, M; Ledbetter, S.; Remuzzi, G. Add-On Anti-TGF-β antibody to ACE Inhibitor Arrests Progressive Diabetic Nephropathy in the Rat. L. Am. Soc. Nephrol. 2003, 14, 1816-1824.