Use of cyr61 in the treatment and diagnosis of human uterine leiomyomas
OwnerZhiming Zhang, Deepak Sampath +2inventors
InventorsZhiming Zhang, Deepak Sampath, Yuan Zhu, Richard Winneker
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Abstract
The present invention relates to methods of inhibiting uterine leiomyoma proliferation and preventing formation of uterine leiomyomas, compounds and compositions that stimulate induction of the Cyr61 gene and compounds that increase Cyr61 activity. The present invention also relates to methods of screening ligands that regulate Cyr61 protein expression. The invention further relates to methods of diagnosing patients with uterine leiomyomas associated with a downregulation of Cyr61 expression. The invention also describes antibodies and related pharmaceutical compositions.
Claims84
A method for inhibiting proliferation of uterine leiomyoma, said method comprising increasing the level of mRNA encoding Cyr61 in said leiomyoma tissue.
A method for inhibiting proliferation of uterine leiomyoma, said method comprising increasing the translation of Cyr61 mRNA in said leiomyoma tissue.
A method for inhibiting proliferation of uterine leiomyoma, said method comprising upregulating the expression of Cyr61 protein in said leiomyoma tissue.
A method for inhibiting proliferation of uterine leiomyoma, said method comprising increasing the activity of Cyr61 protein in said leiomyoma tissue.
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.
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.
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.
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.
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.
An antibody which binds to Cyr61.
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.
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.
A transgenic non-human animal having a uterus, said animal comprising DNA which can be induced to overexpress Cyr61 in said uterus.
A transgenic non-human animal as defined in claim 27, wherein the animal is mouse.
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.
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.
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.
An expression vector comprising the nucleic acid as depicted in FIG. 6 operably associated with an expression control sequence.
A pharmaceutical composition comprising Cyr61 protein or a fragment thereof as depicted by the amino acid sequence in FIG. 7.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
A method for inhibiting proliferation of uterine leiomyoma, said method comprising increasing the level of Cyr61 in leiomyoma tissue.
A method for preventing uterine leiomyoma formation, said method comprising increasing the level of Cyr61 in leiomyoma tissue.
Dependencies are inferred from the claim text.