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1. WO2006096626 - USE OF OPIOID ANTAGONISTS TO ATTENUATE ENDOTHELIAL CELL PROLIFERATION AND MIGRATION

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[ EN ]

CLAIMS
I . A method of treatment, comprising administering to a subject with a disorder characterized by unwanted migration or proliferation of endothelial cells an effective amount of an opioid antagonist.
2. The method of claim 1 , wherein the unwanted migration or proliferation of endothelial cells is unwanted migration or proliferation of vascular endothelial cells.
3. The method of claim 1, wherein the opioid antagonist is a peripheral opioid antagonist.
4. The method of claim 2, wherein the unwanted migration or proliferation of vascular endothelial cells is unwanted angiogenesis.
5. The method of claim 4, wherein the disorder is a cancer.
6. The method of claim 5, wherein the effective amount is such that the subject has effective circulating blood plasma levels of the opioid antagonist continuously for at least 1 week, at least 2 weeks, at least three weeks and, preferably, at least 4 weeks.
7. The method of claim 5, further comprising co-administering to the subject an effective amount of an anti-cancer agent.
8. The method of claim 7, wherein the anti-cancer agent is an anti- neovascularization agent.
9. The method of claim 8, wherein the anti-neovascularization agent is an anti-VEGF monoclonal antibody
10. The method of claim 4, wherein the disorder is diabetes.
I I. The method of claim 4, wherein the disorder is sickle cell anemia.
12. The method of claim 4, wherein the disorder is a vascular wound.
13. The method of claim 4, wherein the disorder is characterized by unwanted ocular neovascularization.
14. The method of claim 13, wherein the disorder is a proliferative
retinopathy.

15. The method of claim 4, wherein the opioid antagonist is a peripheral opioid antagonist.
16. The method of claim 2, wherein the subject is taking concurrent opioid therapy.
17. The method of claim 2, wherein the subject is not taking concurrent opioid therapy
18. The method of claim 2, wherein the subject is taking concurrent chronic opioid therapy.
19. The method of claim 2, wherein the subj ect is not taking concurrent chronic opioid therapy.
20. The method of claim 3, wherein the opioid antagonist is selected from the group consisting of: quaternary or tertiary morphinan derivative, a piperidine-N-alkylcarboxylate, and a quaternary benzomorphan
21. The method of claim 20, wherein the peripheral opioid antagonist is methy ^naltrexone .
22. The method of claim 20, wherein the peripheral opioid antagonist is alvimopan.
23. A method of inhibiting VEGF activity in endothelial cells, comprising contacting the cells with an effective amount of an opioid antagonist.

24. A method of inhibiting exogenous opioid-induced cellular migration or proliferation in endothelial cells, comprising contacting the cells with an effective amount of an opioid antagonist.
25. A method of inhibiting Rho A activation in endothelial cells, comprising contacting the cells with an effective amount of an opioid antagonist.

26. A method of attenuating unwanted migration and/or proliferation of endothelial cells, comprising contacting the cells with an effective amount of an opioid antagonist.
27. The method of claim 1, wherein an amount of the opioid antagonist is administered to a human cancer patient, which amount is effective to attenuate the unwanted migration and/or proliferation.

28. A method of reducing the risk of recurrence of a cancer or tumor after medical intervention, comprising co-administering an opioid antagonist to a cancer patient at the time of the intervention.