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1. (WO2010078042) COMPOSITIONS AND METHODS TO PREVENT CANCER WITH CUPREDOXINS
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

What is claimed is:

1. A pharmaceutical composition comprising: a first chemopreventive agent that is a truncation of azurin, wherein the truncation comprises one or more of the amino acid sequences selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 25; and a second chemopreventive agent.

2. The pharmaceutical composition of claim 1, wherein the second chemopreventive agent is an antiestrogen.

3. The pharmaceutical composition of claim 2, wherein the second chemopreventive agent is selected from the group consisting of Tamoxifen, fenretinide, and aromatase inhibitors.

4. The pharmaceutical composition of claim 1, wherein the truncation binds to one or more binding sites of p53 selected from the group consisting of amino acids 1-17, 24-31, 80-276, and 297-305.

5. The pharmaceutical composition of claim 1 , wherein the truncation binds to the N-terminal binding domain of p53.

6. The pharmaceutical composition of claim 1 , wherein the truncation binds to the DNA binding domain of p53.

7. The pharmaceutical composition of claim 1, wherein the truncation comprises SEQ ID NO 2.

8. The pharmaceutical composition of claim 1, wherein the truncation consists of SEQ ID NO 2.

9. The pharmaceutical composition of claim 1 wherein the truncation comprises a sequence selected from the group consisting of SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, and SEQ ID NO: 35.

10. The pharmaceutical composition of claim 1, further comprising a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10, wherein the pharmaceutically acceptable carrier is suitable for intravenous administration.

12. The pharmaceutical composition of claim 10, wherein the truncation comprises SEQ ID NO: 2.

13. The pharmaceutical composition of claim 10, wherein the truncation consists of SEQ ID NO: 2.

14. A method comprising treating a mammalian patient by administering to the patient a therapeutically effective amount of the composition of claim 10.

15. The method of claim 14, wherein the patient is human.

16. The method of claim 14, wherein the patient is at a higher risk to develop cancer than the general population.

17. The method of claim 16, wherein the cancer is selected from melanoma, breast, pancreas, glioblastoma, astrocytoma, lung, colorectal, neck and head, bladder, prostate, skin, and cervical cancer.

18. The method of claim 16, wherein the patient has at least one high risk feature selected from the group consisting of smoking, poor diet, alcohol consumption, hormone replacement therapy, higher body mass index, nulliparity, betal nut use, frequent mouthwash use, exposure to human papillomavirus, childhood and chronic sun exposure, early age of first intercourse, multiple sexual partners, oral contraceptive use, a family history of cancer, gene carrier status of BRCAl and BRCA2, prior history of breast neoplasia, familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), red or blond hair and fair-skinned phenotype, xeroderma pigmentosum, exposure to radon, polycyclic aromatic hydrocarbons, nickel, chromate, arsenic, asbestos, chloromethyl ethers, benzo[a]pyrene, radiation, or aromatic amines from rubber or paint occupational exposure, chronic obstructive pulmonary disease with airflow obstruction, chronic bladder infections, schistosomiasis, older age, and immunocompromised status.

19. The method of claim 14, wherein the patient has premalignant lesions.

20. The method of claim 14, wherein the patient has been cured of cancer or premalignant lesions.

21. The method of claim 14, wherein the pharmaceutical composition is administered by a mode selected from the group consisting of intravenous injection, intramuscular injection, subcutaneous injection, inhalation, topical administration, transdermal patch, suppository, vitreous injection and oral.

22. The method of claim 21 , wherein the mode is intravenous inj ection.

23. A kit comprising the composition of claim 10 in a vial.

24. A method comprising: administering to a mammalian patient a first chemopreventive agent that is a truncation of azurin, wherein the truncation comprises one or more of the amino acid sequences selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 25; and administering to the mammalian patient a second chemopreventive agent.

25. The method of claim 24, wherein the second chemopreventive agent is an antiestrogen.

26. The method of claim 25, wherein the second chemopreventive agent is selected from the group consisting of Tamoxifen, fenretinide, and aromatase inhibitors.

27. The method of claim 24, wherein the truncation binds to one or more binding sites of p53 selected from the group consisting of amino acids 1-17, 24-31, 80-276, and 297-305.

28. The method of claim 24, wherein the truncation binds to the N-terminal binding domain of p53.

29. The method of claim 24, wherein the truncation binds to the DNA binding domain of p53.

30. The method of claim 24, wherein the truncation consists of SEQ ID NO 2.

31. The method of claim 24, wherein the truncation comprises SEQ ID NO: 2.

32. The method of claim 24, wherein the truncation comprises a sequence selected from the group consisting of SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, and SEQ ID NO: 35.

33. A method comprising increasing the expression of p53 in mammary cells by administering to the cells at least one chemopreventive agent that is a truncation of azurin, wherein the truncation comprises one or more of the amino acid sequences selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 25, and administering an antiestrogen, in any order.

34. The method of claim 33, wherein the antiestrogen is selected from the group consisting of Tamoxifen, fenretinide, and aromatase inhibitors.

35. The method of claim 33, wherein the truncation binds to one or more binding sites of p53 selected from the group consisting of amino acids 1-17, 24-31, 80-276, and 297- 305.

36. The method of claim 33, wherein the truncation binds to the N-terminal binding domain of p53.

37. The method of claim 33, wherein the truncation binds to the DNA binding domain of p53.

38. The method of claim 33, wherein the truncation consists of SEQ ID NO: 2.

39. The method of claim 33, wherein the truncation comprises SEQ ID NO: 2.

40. The method of claim 33, wherein the truncation comprises a sequence selected from the group consisting of SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, and SEQ ID NO: 35.

41. A method comprising reducing the dose-related toxicity of Tamoxifen without decreasing its chemopreventive effects by administering to a mammalian patient a therapeutically effective dose of Tamoxifen and administering to the patient a therapeutically effective dose of at least one chemopreventive agent that is a truncation of azurin, wherein the truncation comprises one or more of the amino acid sequences selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 25, in any order.

42. The method of claim 41, wherein the dose of Tamoxifen and dose of the truncation are administered at or around the same time.

43. The method of claim 41 , wherein the truncation binds to one or more binding sites of p53 selected from the group consisting of amino acids 1-17, 24-31, 80-276, and 297-305.

44. The method of claim 41 , wherein the truncation binds to the N-terminal binding domain of p53.

45. The method of claim 41 , wherein the truncation binds to the DNA binding domain of p53.

46. The method of claim 41 , wherein the truncation consists of SEQ ID NO: 2.

47. The method of claim 41, wherein the truncation comprises SEQ ID NO: 2.

48. The method of claim 41, wherein the truncation comprises a sequence selected from the group consisting of SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO:32, SEQ ID NO: 33, SEQ ID NO: 34, and SEQ ID NO: 35.

49. A method comprising decreasing estrogen receptor binding to p53 in mammalian cells by administering to the mammalian cells at least one chemopreventive agent that is a truncation of azurin, wherein the truncation comprises one or more of the amino acid sequences selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 25, and administering an antiestrogen, in any order.

50. The method of claim 49, wherein the antiestrogen is selected from the group consisting of Tamoxifen, fenretinide, and aromatase inhibitors.

51. The method of claim 49, wherein the truncation binds to one or more binding sites of p53 selected from the group consisting of amino acids 1-17, 24-31, 80-276, and 297-305.

52. The method of claim 49, wherein the truncation binds to the N-terminal binding domain of p53.

53. The method of claim 49, wherein the truncation binds to the DNA binding domain of p53.

54. The method of claim 49, wherein the truncation consists of SEQ ID NO: 2.

55. The method of claim 49, wherein the truncation comprises SEQ ID NO: 2.

56. The method of claim 49, wherein the truncation comprises a sequence selected from the group consisting of SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO:32, SEQ ID NO: 33, SEQ ID NO: 34, and SEQ ID NO: 35.