Claims
- 1. A method for treatment of a patient with neoplasia comprising administering to the patient an effective amount of a compound identified by
determining cyclooxygenase (COX) inhibitory activity of the compound; and determining cGMP-specific phosphodiesterase (“PDE”) inhibition activity of the compound against cGMP-specific PDE enzymatic activity from adenocarcinoma cells; wherein low COX inhibitory activity and high inhibition of said cGMP-PDE activity identifies that the compound has potential for treating neoplasia.
- 2. The method of claim 1, wherein the identification further comprises
determining whether the compound inhibits tumor cell growth in a culture; wherein inhibition of tumor cell growths further identifies that the compound has potential for treating neoplasia.
- 3. The method of claim 1, wherein the identification further comprises
determining whether the compound induces apoptosis of a tumor cell; wherein induction of apoptosis further identifies that the compound has potential for treating neoplasia.
- 4. The method of claim 3, wherein the identification further comprises
determining whether the compound inhibits tumor cell growth in a sample; wherein inhibition of tumor cell growth further identifies that the compound has potential for treating neoplasia.
- 5. A method for treatment of a patient with neoplasia comprising administering to the patient an effective amount of a compound selected by
determining neoplastic cell growth inhibitory activity of the compound; determining cGMP-specific PDE inhibition activity of the compound against cGMP-specific PDE enzymatic activity from adenocarcinoma cells; and selecting a compound that exhibits growth inhibitory activity and said cGMP-specific enzyme inhibitory activity.
- 6. The method of claim 5, wherein said compound is further selected by
determining whether the compound induces apoptosis in a cell; and selecting a compound that induce apoptosis.
- 7. The method of claim 6, wherein said compound is further selected by
determining whether the COX inhibitory activity of the compound; and selecting compounds with low COX inhibitory activity relative to said PDE-inhibitory activity.
- 8. The method of claim 7, wherein the COX inhibitory activity of the compound is determined by
contacting the compound with a cyclooxygenase; and measuring the change, if any, of cyclooxygenase activity; wherein a decrease in cyclooxygenase activity correlates to a decrease in prostaglandin synthetase activity.
- 9. The method of claim 7, wherein the COX inhibitory activity of the compound is determined by
contacting the compound with a cell which secretes PGE-2; and measuring the decrease, if any, of the PGE-2 secretion from the cell; wherein a decrease in PGE-2 secretion correlates to a decrease in prostaglandin synthetase activity.
- 10. A method for treatment of a patient with neoplasia comprising administering to the patient an effective amount of a compound identified by
determining the COX inhibitory activity of the compound; determining the cGMP-specific PDE inhibition activity of the compound; and identifying the compound for use in treating neoplasia in the patient in need thereof if the compound exhibits said PDE inhibition activity and has COX inhibitory activity lower that said PDE inhibition activity.
- 11. The method of claim 10 wherein said compound is further identified by determining the growth inhibitory activity of the compounds; and identifying those compounds with phosphodiesterase inhibitory activity substantially greater than COX inhibitory activity at concentrations exhibiting substantial growth inhibitory activity.
- 12. The method of claim 11 wherein the growth inhibitory activity is determined by the reduction of the number of cells in a sample.
- 13. The method of claim 11 wherein the growth inhibitory activity is determined by inducing apoptosis in a sample.
- 14. A method for treatment of a patient with neoplasia comprising administering to the patient an effective amount of a compound selected by
selecting a compound with cGMP-specific PDE inhibiting activity; evaluating neoplastic cell growth inhibiting activity of the compound; and identifying the compound that exhibits cGMP-specific PDE inhibiting activity and neoplastic cell growth inhibiting activity wherein said compound inhibits neoplasia without substantially inhibiting the growth of normal cells.
BACKGROUND OF THE INVENTION
[0001] This invention provides a method for the treatment and prevention of pre-cancerous and cancerous lesions in mammals. This application is a continuation of Ser. No. 09/602,980 which is a continuation in part of Ser. No. 09/216,070 filed Dec. 18, 1998 which is a continuation in part of Ser. No. 09/046,739 filed Mar. 24, 1998 which is a continuation in part of Ser. No. 08/866,027 filed May 30, 1997 (now U.S. Pat. No. 5,858,694).
Continuations (1)
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Number |
Date |
Country |
Parent |
09602980 |
Jun 2000 |
US |
Child |
10253849 |
Sep 2002 |
US |
Continuation in Parts (3)
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Number |
Date |
Country |
Parent |
09216070 |
Dec 1998 |
US |
Child |
09602980 |
Jun 2000 |
US |
Parent |
09046739 |
Mar 1998 |
US |
Child |
09216070 |
Dec 1998 |
US |
Parent |
08866027 |
May 1997 |
US |
Child |
09046739 |
Mar 1998 |
US |