Claims
- 1. A method for inhibiting proliferation of uterine leiomyoma, said method comprising increasing the level of mRNA encoding Cyr61 in said leiomyoma tissue.
- 2. A method for inhibiting proliferation of uterine leiomyoma, said method comprising increasing the translation of Cyr61 mRNA in said leiomyoma tissue.
- 3. A method for inhibiting proliferation of uterine leiomyoma, said method comprising upregulating the expression of Cyr61 protein in said leiomyoma tissue.
- 4. A method for inhibiting proliferation of uterine leiomyoma, said method comprising increasing the activity of Cyr61 protein in said leiomyoma tissue.
- 5. A method for preventing uterine leiomyoma in normal myometrial tissue, said method comprising maintaining a uterine leiomyoma preventing level of mRNA encoding Cyr61 in said myometrial tissue.
- 6. A method for preventing uterine leiomyoma formation in normal myometrial tissue, said method comprising maintaining a uterine leiomyoma preventing level of translation activity of Cyr61 mRNA in said myometrial tissue.
- 7. A method for preventing uterine leiomyoma formation in normal myometrial tissue, said method comprising maintaining a uterine leiomyoma preventing level of expression of Cyr61 protein in said myometrial tissue.
- 8. A method for preventing uterine leiomyoma formation in normal myometrial tissue, said method comprising maintaining a uterine leiomyoma preventing level of activity of Cyr61 protein in said myometrial tissue.
- 9. A method for preventing uterine leiomyoma formation in normal myometrial tissue, said method comprising maintaining a uterine leiomyoma preventing level of affinity of Cyr61 protein for basic fibroblast growth factor or heparin binding epidermal growth factor in said myometrial tissue.
- 10. An antibody which binds to Cyr61.
- 11. An antibody as defined in claim 10, which selectively recognizes amino acids 371-381 of the amino acid sequence depicted in FIG. 7.
- 12. An antibody as defined in claim 10, which is chimeric.
- 13. An antibody as defined in claim 10, which is anti-idiotypic.
- 14. An antibody as defined in claim 13, which is conjugated to a pharmaceutically active compound.
- 15. An antibody as defined in claim 14, wherein said pharmaceutically active compound comprises calicheamicin.
- 16. An antibody as defined in claim 10, which is a monoclonal antibody.
- 17. An antibody as defined in claim 16, which is humanized.
- 18. An antibody as defined in claim 16, which is chimeric.
- 19. An antibody as defined in claim 16, which is anti-idiotypic.
- 20. An antibody as defined in claim 19, which is conjugated to a pharmaceutically active compound.
- 21. An antibody as defined in claim 20, wherein said pharmaceutically active compound comprises calicheamicin.
- 22. A method for diagnosing uterine leiomyomas, said method comprising comparing the level of Cyr61 present in suspect myometrium tissue to the level of Cyr61 in normal myometrium tissue autologous to said suspect myometrium tissue, whereby a lower level of Cyr61 in said suspect tissue than the level of Cyr61 in said normal tissue indicates that said suspect tissue comprises uterine leiomyoma.
- 23. The method as defined in claim 22, wherein said level of Cyr61 is determined by exposing said suspect tissue and said normal tissue to a Cyr61 antibody that selectively recognizes the Cyr61 protein and comparing the amount of antibody bound by each tissue, whereby a lower level of antibody bound by said suspect tissue than the level of antibody bound by said normal tissue indicates that said suspect tissue comprises uterine leiomyoma.
- 24. A method for screening for a compound which inhibits proliferation or prevents formation of uterine leiomyoma, said method comprising comparing a first amount of Cyr61 expressed by leiomyoma cells exposed to said compound to a second amount of Cyr61 expressed by said uterine leiomyoma cells that have not been exposed to said compound; whereby a greater first amount than said second amount indicates that said compound may inhibit or prevent uterine leiomyoma.
- 25. A transgenic non-human animal having a uterus, said animal comprising DNA which can be induced to overexpress Cyr61 in said uterus.
- 26. A transgenic non-human animal as defined in claim 25, wherein the DNA is human.
- 27. A transgenic non-human animal as defined in claim 27, wherein the animal is mouse.
- 28. A kit for diagnosing uterine leiomyoma, said kit comprising an antibody as defined in claim 10.
- 29. A method for screening compounds that regulate Cyr61 mRNA transcription through a receptor, said method comprising comparing the level of Cyr61 mRNA in a first population of cells, sufficient to transcribe a detectable amount of mRNA encoding Cyr61, when said cells are contacted with a test compound to the level of Cyr61 mRNA in a second population of cells, sufficient to transcribe a detectable amount of mRNA encoding Cyr61, not contacted with said test compound, whereby a higher level of mRNA encoding Cyr61 in said first population of cells than the level of mRNA encoding Cyr61 in said second population of cells indicates that said test compound may regulate Cyr61 mRNA transcription.
- 30. A method for detecting the presence of uterine leiomyoma, said method comprising comparing the level of Cyr61 mRNA isolated from suspect uterine leiomyoma tissue to the level of Cyr61 mRNA isolated from normal myometrium tissue; wherein a lower level of Cyr61 mRNA from said suspect uterine leiomyoma tissue than the level of Cyr61 mRNA from said normal tissue indicates the presence of uterine leiomyoma.
- 31. A method for detecting the presence of uterine leiomyoma, said method comprising comparing the level of Cyr61 in suspect uterine leiomyoma tissue to the level of Cyr61 protein in normal myometrium tissue; wherein a lower level of Cyr61 protein in said suspect tissue than the level of Cyr61 protein in said normal tissue indicates the presence of uterine leiomyoma.
- 32. An antibody as defined in claim 10, which is conjugated to an anti-leiomyoma agent.
- 33. An expression vector comprising the nucleic acid as depicted in FIG. 6 operably associated with an expression control sequence.
- 34. An expression vector as defined in claim 33, wherein said expression control sequence is an estrogen response element.
- 35. An expression vector as defined in claim 33, wherein said expression control sequence is a basic fibroblast growth factor response element.
- 36. A pharmaceutical composition comprising an expression vector as defined in claim 33 in an amount effective to express a therapeutically effective amount of Cyr61.
- 37. A method for preventing uterine leiomyoma formation in normal myometrial tissue, said method comprising administering a pharmaceutical composition as defined in claim 36 to a subject in whom prevention of uterine leiomyoma is desired.
- 38. A method for inhibiting proliferation of uterine leiomyoma, said method comprising administering a pharmaceutical composition as defined in claim 36 to a subject in whom inhibiting the proliferation of uterine leiomyoma is desired.
- 39. A pharmaceutical composition comprising Cyr61 protein or a fragment thereof as depicted by the amino acid sequence in FIG. 7.
- 40. A method for preventing uterine leiomyoma formation, said method comprising administering the pharmaceutical composition as defined in claim 39 to a subject in whom prevention of uterine leiomyoma is desired.
- 41. A method for inhibiting proliferation of uterine leiomyoma, said method comprising administering a pharmaceutical composition as defined in claim 39 to a subject in whom inhibiting the proliferation of uterine leiomyoma is desired.
- 42. A method for inhibiting proliferation of uterine leiomyoma, said method comprising administering to a subject an amount of a compound effective to stimulate the synthesis of mRNA encoding Cyr61 in leiomyoma tissue.
- 43. A method as defined in claim 42, wherein said compound is an estrogen receptor antagonist.
- 44. A method for inhibiting proliferation of uterine leiomyoma, said method comprising administering to a subject, an amount of a compound effective to stimulate the translation of mRNA encoding Cyr61 in leiomyoma tissue.
- 45. A method as defined in claim 44, wherein said compound is an estrogen receptor antagonist.
- 46. A method for inhibiting proliferation of uterine leiomyoma, said method comprising administering to a subject, an amount of a compound effective to upregulate the expression of Cyr61 protein in leiomyoma tissue.
- 47. A method as defined in claim 46, wherein said compound is an estrogen receptor antagonist.
- 48. A method for inhibiting proliferation of uterine leiomyoma, said method comprising administering to a subject an amount of a compound effective to increase the activity of Cyr61 protein in leiomyoma tissue.
- 49. A method as defined in claim 48, wherein said compound is an estrogen receptor antagonist.
- 50. A method for preventing uterine leiomyoma formation in normal myometrial tissue, said method comprising administering to a subject an amount of a compound effective to maintain a uterine leiomyoma preventing level of synthesis of mRNA encoding Cyr61 in said myometrial tissue.
- 51. A method as defined in claim 50, wherein said compound is an estrogen receptor antagonist.
- 52. A method for preventing uterine leiomyoma formation in normal myometrial tissue, said method comprising administering to a subject, an amount of a compound effective to maintain a uterine leiomyoma preventing level of translation activity of Cyr61 mRNA in said myometrial tissue.
- 53. A method as defined in claim 52, wherein said compound is an estrogen receptor antagonist.
- 54. A method for preventing uterine leiomyoma formation in normal myometrial tissue, said method comprising administering to a subject, an amount of a compound effective to maintain a uterine leiomyoma preventing level of expression of Cyr61 protein in leiomyoma tissue.
- 55. A method as defined in claim 54, wherein said compound is an estrogen receptor antagonist.
- 56. A method for preventing uterine leiomyoma formation in normal myometrial tissue, said method comprising administering to a subject an amount of a compound effective to maintain a uterine leiomyoma preventing level of activity of Cyr61 protein in said myometrial tissue.
- 57. A method as defined in claim 56, wherein said compound is an estrogen receptor antagonist.
- 58. A method for preventing uterine leiomyoma formation in normal myometrial tissue, said method comprising administering to a subject an amount of a compound effective to maintain a uterine leiomyoma preventing level of affinity of Cyr61 protein for basic fibroblast growth factor or heparin binding epidermal growth factor in said myometrial tissue.
- 59. A method as defined in claim 58, wherein said compound is an estrogen receptor antagonist.
- 60. A method as defined in claim 42, wherein said compound also downregulates the synthesis of mRNA encoding at least one member selected from the group consisting of IGF I and IGF II in leiomyoma tissue.
- 61. A method as defined in claim 44, wherein said compound also downregulates the translation of mRNA encoding at least one member selected from the group consisting of IGF I and IGF II in leiomyoma tissue.
- 62. A method as defined in claim 46, wherein said compound also downregulates the expression of protein encoding at least one member selected from the group consisting of IGF I and IGF II in leiomyoma tissue.
- 63. A method as defined in claim 48, wherein said compound also decreases the activity of at least one member selected from the group consisting of IGF I and IGF II in leiomyoma tissue.
- 64. A method as defined in claim 50, wherein said compound also downregulates the synthesis of mRNA encoding at least one member selected from the group consisting of IGF I and IGF II in said myometrial tissue.
- 65. A method as defined in claim 52, wherein said compound also downregulates the translation of mRNA encoding at least one member selected from the group consisting of IGF I and IGF II in said myometrial tissue.
- 66. A method as defined in claim 54, wherein said compound also downregulates the expression of at least one member selected from the group consisting of IGF I and IGF II in said myometrial tissue.
- 67. A method as defined in claim 56, wherein said compound decreases the activity of at least one member selected from the group consisting of IGF I and IGF II in said myometrial tissue.
- 68. A method as defined in claim 42, wherein said compound also downregulates the synthesis of mRNA encoding at least one member selected from the group consisting of basic fibroblast growth factor and heparin binding epidermal growth factor in leiomyoma tissue.
- 69. A method as defined in claim 44, wherein said compound also downregulates the translation of mRNA encoding at least one member selected from the group consisting of basic fibroblast growth factor and heparin binding epidermal growth factor in leiomyoma tissue.
- 70. A method as defined in claim 46, wherein said compound also downregulates the expression of at least one member selected from the group consisting of basic fibroblast growth factor and heparin binding epidermal growth factor in leiomyoma tissue.
- 71. A method as defined in claim 48, wherein said compound decreases the activity of at least one member selected from the group consisting of basic fibroblast growth factor and heparin binding epidermal growth factor in leiomyoma tissue.
- 72. A method as defined in claim 50, wherein said compound also downregulates the synthesis of mRNA encoding at least one member selected from the group consisting of basic fibroblast growth factor and heparin binding epidermal growth factor in said myometrial tissue.
- 73. A method as defined in claim 52, wherein said compound also downregulates the translation of mRNA encoding at least one member selected from the group consisting of basic fibroblast growth factor and heparin binding epidermal growth factor in said myometrial tissue.
- 74. A method as defined in claim 54, wherein said compound also downregulates the expression of at least one member selected from the group consisting of basic fibroblast growth factor and heparin binding epidermal growth factor in said myometrial tissue.
- 75. A method as defined in claim 56, wherein said compound decreases the activity of at least one member selected from the group consisting of basic fibroblast growth factor and heparin binding epidermal growth factor in said myometrial tissue.
- 76. A method as defined in claim 60, wherein the synthesis of mRNA is downregulated by antisense nucleic acid.
- 77. A method as defined in claim 64, wherein the synthesis of mRNA is downregulated by antisense nucleic acid.
- 78. A method as defined in claim 68, wherein the synthesis of mRNA is downregulated by antisense nucleic acid.
- 79. A method as defined in claim 72, wherein the synthesis of mRNA is downregulated by antisense nucleic acid.
- 80. A method for inhibiting proliferation of uterine leiomyoma, said method comprising administering to a subject an amount of a compound effective to modulate Cyr61 protein binding to an integrin receptor.
- 81. A method for preventing uterine leiomyoma formation, said method comprising administering to a subject an amount of a compound effective to modulte Cyr61 protein binding to an integrin receptor.
- 82. A method for inhibiting proliferation of uterine leiomyoma, said method comprising increasing the level of Cyr61 in leiomyoma tissue.
- 183. A method for preventing uterine leiomyoma formation, said method comprising increasing the level of Cyr61 in leiomyoma tissue.
- 184. A pharmaceutical composition as defined in claim 39, wherein said fragment retains Cyr61 functional activity.
PRIORITY
[0001] This application claims priority under 35 U.S.C. § 119 from provisional patent application Serial No. 60/236,887, filed Sep. 29, 2001; which is hereby incorporated by reference in its entirety.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/US01/30783 |
9/28/2001 |
WO |
|