Compositions and methods for treating colorectal polyps and cancer

• US 20030083339A1
• Filed: 04/26/2002
• Published: 05/01/2003
• Est. Priority Date: 04/26/2001
• Status: Abandoned Application

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Tamura, Masaaki
• Application Number:
  US10/133,056
• Publication Number:
  US 20030083339A1
• Time in Patent Office: Days
• US Class Current: 514/263.4
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/401 Proline; Derivatives thereof, e.g. captopril
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 38/085 Angiotensins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/111 spanning the whole gene, or a large part of it
• CPC Class Codes: C12N 2799/022 where the vector is derived from an adenovirus
• CPC Class Codes: C12N 2799/027 where the vector is derived from a retrovirus
• CPC Class Codes: G01N 33/57419 of colon

Abstract

A method of decreasing a biological function of an AT₂ receptor in a subject in need thereof is disclosed. The method includes administering an effective amount of a therapeutic agent to the subject to decrease a biological function of an AT₂ receptor. Cancer therapy, particularly colorectal cancer therapy, by the method is also disclosed.

Claims

1. A method of decreasing a biological function of an AT₂ receptor in a subject in need thereof, comprising administering an effective amount of an therapeutic agent to the subject to decrease a biological function of an AT₂ receptor.

2. The method of claim 1, wherein the subject is a mammal.

3. The method of claim 2, wherein the mammal is a human.

4. The method of claim 2, wherein the mammal is a mouse.

5. The method of claim 1, wherein the therapeutic agent is PD 123319.

6. The method of claim 1, wherein the administration is orally, intramuscularly, subcutaneously, intraperitoneally, intravenously, intradermally or mucosally.

7. A method of preventing the development of a cancer in a subject having an AT₂ receptor, the method comprising:

(a) providing a subject having an AT₂ receptor; and

(b) administering to the subject a therapeutically effective amount of an AT₂ receptor antagonist, whereby the development of a cancer in a subject having an AT₂ receptor is prevented.

8. The method of claim 7, wherein the subject is a mammal.

9. The method of claim 8, wherein the mammal is a human.

10. The method of claim 8, wherein the mammal is a mouse.

11. The method of claim 7, wherein the cancer is a colorectal cancer.

12. The method of claim 7, wherein AT₂ receptor antagonist is PD 123319.

13. The method of claim 7, wherein the administration is orally, intramuscularly, subcutaneously, intraperitoneally, intravenously, intradermally or mucosally.

14. A method of treating a cancer in a subject having an AT₂ receptor, the method comprising:

(a) providing a subject having a cancer and an AT₂ receptor;

(b) administering to the subject a therapeutically effective amount of an AT₂ receptor antagonist, whereby a cancer in a subject having an AT₂ receptor is treated.

15. The method of claim 14, wherein the subject is a mammal.

16. The method of claim 15, wherein the mammal is a human.

17. The method of claim 15, wherein the mammal is a mouse.

18. The method of claim 14, wherein AT₂ receptor antagonist is PD 123319.

19. The method of claim 14, wherein the cancer is a colorectal cancer.

20. The method of claim 14, wherein the administration is orally, intramuscularly, subcutaneously, intraperitoneally, intravenously, intradermally or mucosally.

21. A method of screening one or more candidate compounds for an ability to prevent or treat a cancer, the method comprising:

(a) providing one or more candidate compounds;

(b) determining a first level of AT₂ receptor biological activity;

(c) contacting one candidate compound with an AT₂ receptor;

(d) determining a second level of AT₂ receptor biological activity;

(e) comparing the first level of AT₂ biological activity with the second level of AT₂ biological activity, wherein a second level that is less than the first level is indicative of a compound having an ability to prevent or treat a cancer; and

(f) repeating steps (b)-(e) for each of the one or more candidate compounds.

22. The method of claim 21, wherein the subject is a mammal.

22-1. The method of claim 22, wherein the mammal is a human.

24. The method of claim 22, wherein the mammal is a mouse.

25. The method of claim 21, wherein AT₂ receptor antagonist is PD 123319.

26. The method of claim 21, wherein the cancer is a colorectal cancer.

27. The method of claim 21, wherein the determining is by employing a technique selected from the group consisting of spectrophotometric detection, radiologic detection and immunologic detection.

28. A method achieving one of treating a cancer and preventing a cancer, the method comprising:

(a) providing subject in need of treatment;

(b) administering an ACE inhibitor to the subject; and

(c) administering an Ang II receptor antagonist to a subject.

29. The method of claim 28, wherein the male subject is a mammal.

30. The method of claim 29, wherein the male subject is a human.

31. The method of claim 29, wherein the male subject is a mouse.

32. The method of claim 28, wherein the ACE inhibitor and the Ang II receptor antagonist are coadministered contemporaneously.

33. The method of claim 32, wherein the coadministering is by injection.

34. The method of claim 28, wherein the cancer is a colorectal cancer.

35. The method of claim 28, wherein the ACE inhibitor is selected from the group consisting of Captopril, Enalapril, Lisinopril, Benazepril, Quinapril, Ramipril, Trandolapril, Moexipril, Fosinopril, Perindep and pharmaceutically acceptable salts thereof.

36. The method of claim 28, wherein the Ang II receptor antagonist is selected from the group consisting of candesartan cilexetil, eprosartan, irbesartan, tasosartan, telmisartan, valsartan, BMS-184699, 3-(2′

-(tetrazol-5-yl)-1,1′

-biphen-4-yl)methyl-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine, BAY 106734, BIBR363, CL329167, E4177, EMD73495, HN65021, HR720, HOE720, LRB081, SC52459, SL910102, UP2696, YM358, EMD66397, ME3221, TAK536, BMS 184698, CGP42112A, CGP49870, CP14R130, E4188, EMD666R4, EXP9954, FRI 153332, GA0050, KT3579, LF70156, LRB057, LY266099, LY301875, PD 123177, PD 126055, SC51757, SC54629, U96849, UK77778, WAY126227, WK1260, WK1492, YH1498, and YM31472, PD 123319, Saralasin, and Losartan.