Claims
- 1. A non-human bone metastasis model animal exhibiting bone metastasis of tumor cells, in which tumor cells capable of inducing bone metastasis have been introduced by peripheral administration.
- 2. The non-human bone metastasis model animal according to claim 1, wherein the tumor cells are human lung cancer or breast cancer derived cells highly expressing PTHrP.
- 3. The non-human bone metastasis model animal according to claim 1, wherein the tumor cells are cells from human lung small cell carcinoma.
- 4. The non-human bone metastasis model animal according to claim 1, which exhibits multi-organ metastasis of tumor cells.
- 5. The non-human bone metastasis model animal according to claim 4, wherein the multi-organ metastases include metastases to one or more organs selected from the group consisting of lung, liver, kidney, and lymph node.
- 6. The non-human bone metastasis model animal according to claim 1, wherein the animal belongs to rodents.
- 7. The non-human bone metastasis model animal according to claim 6, wherein the animal is mouse.
- 8. The non-human bone metastasis model animal according to claim 7, wherein the animal is immunodeficient mouse.
- 9. The non-human bone metastasis model animal according to claim 8, wherein the animal is SCID mouse.
- 10. A method for producing a non-human animal exhibiting bone metastasis of tumor cells, comprising the steps of:
(i) providing a non-human animal having reduced immunity; and (ii) introducing tumor cells capable of inducing bone metastasis into the animal by peripheral administration.
- 11. The method according to claim 10, wherein the tumor cells are human lung cancer- or breast cancer-derived cells highly expressing PTHrP.
- 12. The method according to claim 10, wherein the tumor cells are cells from human lung small cell carcinoma.
- 13. The method according to claim 10, wherein the step of providing a non-human animal having reduced immunity includes a step of inactivating NK cells in the animal.
- 14. The method according to claim 10, wherein the step of providing a non-human animal having reduced immunity includes a step of reducing the number of NK cells in the animal.
- 15. The method according to claim 10, wherein the step of providing a non-human animal having reduced immunity includes a step of depleting NK cells in the animal.
- 16. The method according to claim 10, wherein the step of providing a non-human animal having reduced immunity includes a step of administering anti-IL-2 receptor antibody to the animal.
- 17. The method according to claim 16, wherein the antibody is anti-IL-2 receptor β-chain antibody.
- 18. The method according to claim 16, wherein the antibody is mouse antibody.
- 19. The method according to claim 10, wherein the step of introducing tumor cells capable of inducing bone metastasis to the animal by peripheral administration includes a step of injecting the tumor cells into the animal intravenously.
- 20. The method according to claim 10, wherein the animal belongs to rodents.
- 21. The method according to claim 10, wherein the animal is mouse.
- 22. The method according to claim 21, wherein the animal is an immunodeficient mouse.
- 23. The method according to claim 21, wherein the animal is SCID mouse.
- 24. A method for evaluating efficiencies of treatment against bone metastasis of tumor cells, comprising the step of:
(i) applying a treatment to the non-human bone metastasis model animal according to any one of claims 1 to 9; and (ii) comparing the size and/or extent of bone metastasis, and/or symptoms resulted from bone metastasis, with control animal.
- 25. Af method for determining the effect of a test substance on bone metastasis, comprising the steps of:
(i) administering the test substance to a non-human bone metastasis model animal according to any of claims 1 to 9; and (ii) comparing the size and/or extent of bone metastasis, and/or symptoms resulted from bone metastasis, with control animal.
- 26. A method of screening a substance for inhibiting and/or preventing bone metastasis of tumor cells, comprising the following steps (i) to (iii):
(i) producing a non-human model animal exhibiting multi-organ metastasis of tumor cells including bone metastasis; (ii) administering a test substance to the model animal; and (iii) measuring inhibitory and/or preventive effect of the test substance on bone metastasis.
- 27. The method according to claim 26, wherein the non-human model animal is produced by introducing tumor cells capable of inducing bone metastasis into the animal by peripheral administration.
- 28. The method according to claim 27, wherein the tumor cells are human lung cancer- or breast cancer-derived cells highly expressing PTHrP.
- 29. The method according to claim 28, wherein the tumor cells are cells derived from human small cell lung carcinoma (SCLC).
- 30. The method according to claim 26, wherein the animal belongs to rodents.
- 31. The method according to claim 30, wherein the animal is a mouse.
- 32. The method according to claim 31, wherein the animal is an iminunodeficient mouse.
- 33. The method according to claim 26, wherein the test substance is a PTHrP antagonist, anti-PTHrP antibody, anti-PTHrP antibody analog or low molecular weight compound.
- 34. A method of evaluating efficiencies of treatment against bone metastasis of tumor cells, comprising the following steps (i) and (ii):
(i) treating a non-human model animal exhibiting multi-organ metastasis of tumor cells including bone metastasis; and (ii) comparing the size and/or extent of bone metastasis, and/or symptoms resulted from bone metastasis, with a control animal.
- 35. A method of using a non-human model animal exhibiting multi-organ metastasis of tumor cells including bone metastasis for determining the effect of a test substance on bone metastasis, comprising the following steps (i) and (ii):
(i) administering the test substance to the animal; and (ii) comparing the size and/or extent of bone metastasis, and/or symptoms resulted from bone metastasis, with a control animal.
- 36. A method of producing a medicament for inhibiting and/or preventing bone metastasis of tumor cells, comprising the following steps (i) and (ii):
(i) identifying a substance capable of inhibiting and/or preventing bone metastasis of tumor cells by the screening method of claim 26; and (ii) mixing the substance identified in (i) with a pharmaceutically acceptable carrier.
- 37. The method according to claim 11, wherein the substance is an anti-PTHrP antibody or anti-PTHrP antibody analog.
Priority Claims (1)
Number |
Date |
Country |
Kind |
2001-140538 |
May 2001 |
JP |
|
Parent Case Info
[0001] This application is a continuation-in-part of U.S. application Ser. No. 09/864,364, filed May 25, 2001, and Japanese Patent Application 2001-140538, filed May 10, 2001, which are herein incorporated by reference for any purpose.
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09864364 |
May 2001 |
US |
Child |
10143364 |
May 2002 |
US |