- 2014-12-01 (x)
- Brattain, Michael G. (x)
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Show moreBackground of the invention: 1. Field of the Invention This invention is concerned with diagnostic methods which assist in classification of tumors by phenotype and with therapeutic intervention tailored to particular tumor phenotypes. In particular this invention concerns mutant forms of type II receptors (RII) for transforming growth factor beta (TGF.beta.) which inactivate growth suppression by TGF.beta., methods for detecting inactivation of TGF.beta. RII receptor and therapeutic methods for restoring tumor suppression by restoring RII function.2. Review of Related ArtTGF.beta. inhibits growth of multiple epithelial cell types, and loss of this negative regulation is thought to contribute to tumor development (Roberts, et al., 1990, In Peptide Growth Factors and Their Receptors. Handbook of Experimental Pharmacology, A. Roberts and M. Sporn, Eds., (Springer-Verlag, Heidelberg) pp. 419-472; Massague, J., 1990, Annu. Rev. Cell Biol., 6:597; Moses, et al., 1990, Cell, 63:247; Filmus, et al., 1993, Curr. Opin. Oncol., 5:123; Markowitz, S., et al., 1994, J. Clin. Invest., 93:1005; Wu, S., et al., 1992, J. Cell. Biol., 116:187; Wu, S., et al., 1993, Cell Growth Differ., 4:115; Park, J., et al., 1994, Proc. Natl. Acad. Sci. U.S.A., 91:8772; Manning, et al., 1991, Oncogene, 6:1471; Hoosein, N., et al., 1989, Exp. Cell Res., 181:442; Geiser, et al., 1992, J. Biol. Chem., 267:2588). Previous studies have demonstrated that TGF.beta. suppresses growth of certain cancer cell lines, that antisense inhibition of TGF.beta. enhances the tumorigenicity of weakly tumorigenic cancer cell lines, and that certain tumor cells can become unresponsive to TGF.beta. (Markowitz, S., et al., 1994, J. Clin. Invest., 93:1005; Wu, S., et al., 1992, J. Cell. Biol., 116:187; Wu, S., et al., 1993, Cell Growth Differ., 4:115; Park, J., et al., 1994, Proc. Natl. Acad. Sci. U.S.A., 91:8772; Manning, et al., 1991, Oncogene, 6:1471; Hoosein, N., et al., 1989, Exp. Cell Res., 181:442; Geiser, et al., 1992, J. Biol. Chem., 267:2588). The TGF.beta. growth inhibitory signal is transduced through two receptors, type I (RI) and type II (RII) which function as a heteromeric complex (Lin, et al., 1992, Cell, 68:775; Moustakas, A., et al., 1993, J. Biol. Chem., 268:22215; Wrana, J., et al., 1992, Cell, 71:1003). Summary of the invention: It is an object of this invention to provide a method for diagnosis or prognosis of cancer by detection of the absence of functional TGF.beta. receptor RII in cells of a patient. It is another object of this invention to provide a nucleotide sequence encoding a mutant form of RII, to provide mutant RII protein and to provide antibodies specifically immunoreactive with mutant RII. It is yet another object of this invention to provide therapeutic methods for treating tumors having inactive RII by replacement gene therapy.
http://www.google.com/patents?vid=USPAT6291237
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Show moreBackground of the invention: 1. Field of the Invention This invention is concerned with diagnostic methods which assist in classification of tumors by phenotype and with therapeutic intervention tailored to particular tumor phenotypes. In particular this invention concerns mutant forms of type II receptors (RII) for transforming growth factor beta (TGF.beta.) which inactivate growth suppression by TGF.beta., methods for detecting inactivation of TGF.beta. RII receptor and therapeutic methods for restoring tumor suppression by restoring RII faction. 2. Review of Related ArtTGF.beta. inhibits growth of multiple epithelial cell types, and loss of this negative regulation is thought to contribute to tumor development (Roberts, et al., 1990, In Peptide Growth Factors and Their Receptors. Handbook of Experimental Pharmacology, A. Roberts and M. Sporn, Eds., (Springer-Verlag, Heidelberg) pp. 419-472; Massague, J., 1990, Annu. Rev. Cell Biol., 6:597; Moses, et al., 1990, Cell, 63:247; Filmus, et al., 1993, Curr. Opin. Oncol., 5:123; Markowitz, S., et al., 1994, J. Clin. Invest., 93:1005; Wu, S., et al., 1992, J. Cell. Biol., 116:187; Wu, S., et al., 1993, Cell Growth Differ., 4:115; Park, J., et al., 1994, Proc. Natl. Acad. Sci. U.S.A., 91:8772; Manning, et al., 1991, Oncogene, 6:1471; Hoosein, N., et al., 1989, Exp. Cell Res., 181:442; Geiser, et al., 1992, J. Biol. Chem., 267:2588). Previous studies have demonstrated that TGF.beta. suppresses growth of certain cancer cell lines, that antisense inhibition of TGF.beta. enhances the tumorigenicity of weakly tumorigenic cancer cell lines, and that certain tumor cells can become unresponsive to TGF.beta. (Markowitz, S., et al., 1994, J. Clin. Invest., 93:1005; Wu, S., et al., 1992, J. Cell. Biol., 116:187; Wu, S., et al., 1993, Cell Growth Differ., 4:115; Park, J., et al., 1994, Proc. Natl. Acad. Sci. U.S.A., 91:8772; Manning, et al., 1991, Oncogene, 6:1471; Hoosein, N., et al., 1989, Exp. Cell Res., 181:442; Geiser, et al., 1992, J. Biol. Chem., 267:2588). The TGF.beta. growth inhibitory signal is transduced through two receptors, type I (RI) and type II (RII) which function as a heteromeric complex (Lin, et al., 1992, Cell, 68:775; Moustakas, A., et al., 1993, J. Biol. Chem., 268:22215; Wrana, J., et al., 1992, Cell, 71:1003). Summary of the invention: It is an object of this invention to provide a method for diagnosis or prognosis of cancer by detection of the absence of functional TGF.beta. receptor RII in cells of a patient.It is another object of this invention to provide a nucleotide sequence encoding a mutant form of RII, to provide mutant RII protein and to provide antibodies specifically immunoreactive with mutant RII.It is yet another object of this invention to provide therapeutic methods for treating tumors having inactive RII by replacement gene therapy.
http://www.google.com/patents?vid=USPAT6630326
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Show moreBackground of the invention: 1. Field of the Invention This invention is concerned with diagnostic methods which assist in classification of tumors by phenotype and with therapeutic intervention tailored to particular tumor phenotypes. In particular this invention concerns mutant forms of type II receptors (RII) for transforming growth factor beta (TGF-.beta.) which inactivate growth suppression by TGF-.beta., methods for detecting inactivation of TGF-.beta. RII receptor and therapeutic methods for restoring tumor suppression by restoring RII function. 2. Review of Related ArtTGF-.beta. inhibits growth of multiple epithelial cell types, and loss of this negative regulation is thought to contribute to tumor development (Roberts, et al., 1990, In Peptide Growth Factors and Their Receptors. Handbook of Experimental Pharmacology, A. Roberts and M. Sporn, Eds., (Springer-Verlag, Heidelberg) pp. 419-472; Massague, J., 1990, Annu. Rev. Cell Biol, 6:597; Moses, et al., 1990, Cell, 63:247; Filmus, et al., 1993, Curr. Opin. Oncol., 5:123; Markowitz, S., et al., 1994, J. Clin. Invest., 93:1005; Wu, S., et al., 1992, J. Cell. Biol., 116:187; Wu, S., et al., 1993, Cell Growth Differ., 4:115; Park, J., et al., 1994, Proc. Natl. Acad. Sci. U.S.A., 91:8772; Manning, et al., 1991, Oncogene, 6:1471; Hoosein, N., et al., 1989, Exp. Cell Res., 181:442; Geiser, et al., 1992, J. Biol. Chem., 267:2588). Previous studies have demonstrated that TGF-.beta. suppresses growth of certain cancer cell lines, that antisense inhibition of TGF-.beta. enhances the tumorigenicity of weakly tumorigenic cancer cell lines, and that certain tumor cells can become unresponsive to TGF-.beta. (Markowitz, S., et al., 1994, J. Clin. Invest., 93:1005; Wu, S., et al., 1992, J. Cell. Biol., 116:187; Wu, S., et al., 1993, Cell Growth Differ., 4:115; Park, J., et al., 1994, Proc. Natl. Acad. Sci. U.S.A., 91:8772; Manning, et al., 1991, Oncogene, 6:1471; Hoosein, N., et al., 1989, Exp. Cell Res., 181:442; Geiser, et al., 1992, J. Biol. Chem., 267:2588). The TGF-.beta. growth inhibitory signal is transduced through two receptors, type I (RI) and type II (RII) which function as a heteromeric complex (Lin, et al., 1992, Cell, 68:775; Moustakas, A., et al., 1993, J. Biol. Chem., 268:22215; Wrana, J., et al., 1992, Cell, 71:1003). Summary of the invention: It is an object of this invention to provide a method for diagnosis or prognosis of cancer by detection of the absence of functional TGF.beta. receptor RII in cells of a patient. It is another object of this invention to provide a nucleotide sequence encoding a mutant form of RII, to provide mutant RII protein and to provide antibodies specifically immunoreactive with mutant RII. It is yet another object of this invention to provide therapeutic methods for treating tumors having inactive RII by replacement gene therapy.
http://www.google.com/patents?vid=USPAT5866323
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