- 2014-12-01 (x)
- Markowitz, Sanford D. (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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Show moreBackground: Colorectal cancer, also referred to herein as colon cancer, is the second leading cause of cancer mortality in the adult American population. An estimated 135,000 new cases of colon cancer occur each year. Although many people die of colon cancer, early stage colon cancers are often treatable by surgical removal (resection) of the affected tissue. Surgical treatment can be combined with chemotherapeutic agents to achieve an even higher survival rate in certain colon cancers. However, the survival rate drops to 5% or less over five years in patients with metastatic (late stage) colon cancer. Effective screening and early identification of affected patients coupled with appropriate therapeutic intervention is proven to reduce the number of colon cancer mortalities. It is estimated that 74,000,000 older Americans would benefit from regular screening for colon cancer and precancerous colon adenomas (together, adenomas and colon cancers may be referred to as colon neoplasias). However, present systems for screening for colon neoplasia are inadequate. For example, the Fecal Occult Blood Test involves testing a stool sample from a patient for the presence of blood. This test is relatively simple and inexpensive, but it often fails to detect colon neoplasia (low sensitivity) and often even when blood is detected in the stool, a colon neoplasia is not present (low specificity). Flexible sigmoidoscopy involves the insertion of a short scope into the rectum to visually inspect the lower third of the colon. Because the sigmoidoscope is relatively short, it is also a relatively uncomplicated diagnostic method. However, nearly half of all colon neoplasia occurs in the upper portions of the colon that can not be viewed with the sigmoidoscope. Colonoscopy, in which a scope is threaded through the entire length of the colon, provides a very reliable method of detecting colon neoplasia in a subject, but colonoscopy is costly, time consuming and requires sedation of the patient. Modem molecular biology has made it possible to identify proteins and nucleic acids that are specifically associated with certain physiological states. These molecular markers have revolutionized diagnostics for a variety of health conditions ranging from pregnancy to viral infections, such as HIV. Researchers generally identify molecular markers for a health condition by searching for genes and proteins that are expressed at different levels in one health condition versus another (e.g. in pregnant women versus women who are not pregnant). Traditional methods for pursuing this research, such as Northern blots and reverse transcriptase polymerase chain reaction, allow a researcher to study only a handful of potential molecular markers at a time. Microarrays, consisting of an ordered array of hundreds or thousands of probes for detection of hundreds or thousands of gene transcripts, allow researchers to gather data on many potential molecular markers in a single experiment.
http://www.google.com/patents?vid=USPAT7118912
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