USE OF CYCLOPAMINE IN THE TREATMENT OF BASAL CELL CARCINOMA AND OTHER TUMORS
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Abstract
This invention concerns the use of cyclopamine in vivo on basal cell carcinomas (BCC'"'"'s) to achieve therapeutic effect by causing differentiation of the tumor cells and, at the same time, apoptotic death and removal of these tumor cells while preserving the normal tissue cells, including the undifferentiated cells of the normal epidermal basal layer and hair follicles. Causation of apoptosis by cyclopamine is by a non-genotoxic mechanism and thus unlike the radiation therapy and most of the currently used cancer chemotherapeutics which act by causing DNA-damage. These novel effects, previously unachieved by a cancer chemotherapeutic, make the use of cyclopamine highly desirable in cancer therapy, in the treatment of BCC'"'"'s and other tumors that use the hedgehog/smoothened signal transduction pathway for proliferation and prevention of apoptosis.
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Citations
71 Claims
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1-43. -43. (canceled)
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44. A method for inducing apoptosis of tumor cells in a tumor-bearing patient, comprising
determining that Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of tumor cells and administering to the patient cyclopamine or a pharmaceutically acceptable salt thereof in a dose that is sufficient to induce apoptosis of said tumor cells and to cause decrease of size or disappearance of the tumor.
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45. A method for treatment of a patient having a tumor wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of the tumor cells, comprising
administering to the patient a medicament comprising cyclopamine or another compound that selectively inhibits Hedgehog/Smoothened signaling, wherein said medicament is administered in a dose that is sufficient to induce apoptosis of said tumor cells and causes decrease of size or disappearance of the tumor.
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47. A method for treatment of a patient having a tumor wherein Hedgehog/Smoothened signaling is utilized for inhibition of differentiation and for inhibition of apoptosis of tumor cells, comprising
administering to the patient a medicament comprising cyclopamine or another compound that selectively inhibits Hedgehog/Smoothened signaling, wherein said medicament is administered in a dose that is sufficient to induce differentiation and apoptosis of said tumor cells and causes decrease of size or disappearance of the tumor.
- 58. A medicament comprising cyclopamine or a pharmaceutically acceptable salt thereof or another compound that selectively inhibits Hedgehog/Smoothened signaling with instructions for effective administration to cause decrease of size or disappearance of a tumor wherein Hedgehog/Smoothened signaling is utilized to prevent apoptosis of the tumor cells and said administration induces apoptosis of the tumor cells to cause decrease of size or disappearance of the tumor.
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60. A method for treatment of a human subject having a tumor wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of the tumor cells, comprising
administering to the subject a medicament comprising cyclopamine or another compound that selectively inhibits Hedgehog/Smoothened signaling, wherein said medicament is administered in a dose that is sufficient to induce apoptosis of said tumor cells and causes decrease of size or disappearance of the tumor.
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61. A method for treatment of a human subject having a tumor wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of the tumor cells, comprising
administering to the subject a medicament comprising cyclopamine or another compound that inhibits Hedgehog/Smoothened signaling by binding to the same biological target to which cyclopamine binds to inhibit Hedgehog/Smoothened signaling, wherein said medicament is administered in a dose that is sufficient to induce apoptosis of said tumor cells and causes decrease of size or disappearance of the tumor.
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62. A method for treatment of a human subject having a tumor wherein Hedgehog/Smoothened signaling is utilized for inhibition of differentiation and for inhibition of apoptosis of the tumor cells, comprising
administering to the subject a medicament comprising cyclopamine or another compound that selectively inhibits Hedgehog/Smoothened signaling, wherein said medicament is administered in a dose that is sufficient to induce differentiation and apoptosis of said tumor cells and causes decrease of size or disappearance of the tumor.
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63. A method for treatment of a human subject having a tumor wherein Hedgehog/Smoothened signaling is utilized for inhibition of differentiation and for inhibition of apoptosis of the tumor cells, comprising
administering to the subject a medicament comprising cyclopamine or another compound that inhibits Hedgehog/Smoothened signaling by binding to the same biological target to which cyclopamine binds to inhibit Hedgehog/Smoothened signaling, wherein said medicament is administered in a dose that is sufficient to induce differentiation and apoptosis of said tumor cells and causes decrease of size or disappearance of the tumor.
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64. A medicament comprising cyclopamine or another compound that selectively inhibits Hedgehog/Smoothened signaling,
with instructions for effective administration to a tumor-bearing human subject for causation of decrease of size or disappearance of the tumor, wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of the tumor cells and said administration induces apoptosis of the tumor cells and causes decrease of size or disappearance of the tumor.
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65. A medicament comprising cyclopamine or another compound that inhibits Hedgehog/Smoothened signaling by binding to the same biological target to which cyclopamine binds to inhibit Hedgehog/Smoothened signaling,
with instructions for effective administration to a tumor-bearing human subject for causation of decrease of size or disappearance of the tumor, wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of the tumor cells and said administration induces apoptosis of the tumor cells and causes decrease of size or disappearance of the tumor.
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66. A medicament comprising cyclopamine or another compound that selectively inhibits Hedgehog/Smoothened signaling,
with instructions for effective administration to a tumor-bearing human subject for causation of decrease of size or disappearance of the tumor, wherein Hedgehog/Smoothened signaling is utilized for inhibition of differentiation and for inhibition of apoptosis of the tumor cells and said administration induces differentiation and apoptosis of the tumor cells and causes decrease of size or disappearance of the tumor.
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67. A medicament comprising cyclopamine or another compound that inhibits Hedgehog/Smoothened signaling by binding to the same biological target to which cyclopamine binds to inhibit Hedgehog/Smoothened signaling,
with instructions for effective administration to a tumor-bearing human subject for causation of decrease of size or disappearance of the tumor, wherein Hedgehog/Smoothened signaling is utilized for inhibition of differentiation and for inhibition of apoptosis of the tumor cells and said administration induces differentiation and apoptosis of the tumor cells and causes decrease of size or disappearance of the tumor.
Specification