Claims
- 1. A method for controlling, treating and/or preventing cancer, malignancies, neoplasm, hyperplasia, hypertrophy, dysplasia and/or tumor angiogenesis, said method comprising:
administering a nitric oxide mimetic to an animal thereof, to control, treat and/or prevent said cancer, malignancies, neoplasm, hyperplasia, hypertrophy, dysplasia and/or tumor angiogenesis.
- 2. The method according to claim 1, wherein said nitric oxide mimetic is administered at a low dose.
- 3. The method according to claim 1, wherein said nitric oxide mimetic is administered at a level which delays and/or reduces development of tolerance to the nitric oxide mimetic and/or unwanted side effects, including headache, flushing and hypotension.
- 4. The method according to claim 1, wherein said nitric oxide mimetic is administered alone or in combination with an antimalignant therapeutic agent.
- 5. The method according to claim 1, wherein said nitric oxide mimetic;
(1) inhibits the metastatic potential of a tumor or malignant cell phenotype preferably by decreasing the invasiveness, progression, growth and/or metastases of cells exhibiting a malignant phenotype; inhibiting the survival and/or growth of cells exhibiting a malignant phenotype; decreasing the progression and/or metastases of cells exhibiting a malignant phenotype; increasing the regression of cells exhibiting a malignant phenotype; and/or facilitating the killing of cells exhibiting a malignant phenotype; (2) maintains a malignant tumor in a dormant or quiescent state at its primary and/or secondary site; (3) enhances the efficacy of, and/or prevents or decreases the resistance to an antimalignant therapeutic modality; or (4) inhibits or prevents tumor angiogenesis in animals at high risk of developing cancer and/or exposed to factors known to decrease nitric oxide activity in an animal, optionally wherein said factors include decreased arginine levels, exposure to nitric oxide synthase antagonists, exposure to nitric oxide scavengers, changes in nitric oxide synthase expression, change in cofactors, glucose deprivation, surgical procedures, administration of anaesthetic agents, administration of pharmacologic agents which alter circulation, traumatic injuries, physical trauma, blood loss, decreased blood volume, or hemorrhage, or combinations thereof.
- 6. The method according to claim 1, wherein the cells exhibiting the malignancies are selected from malignant cells, invasive cells, cells and tissue[s] that facilitate the malignant process, and combinations thereof, optionally wherein the malignant cell phenotype is controlled, treated or prevented by improving response to an antimalignant therapeutic modality.
- 7. The method according to claim 1, wherein cancer is diagnosed or monitored by measuring a tumor selective marker present in said animal.
- 8. The method according to claim 7, wherein said nitric oxide mimetic decreases or decelerates increases of the level of said tumor marker.
- 9. The method according to claim 1, wherein said cancer comprises gastric cancer, gastrointestinal cancer, testicular cancer, prostate cancer, prostatic adenocarcinoma, breast cancer, metastatic melanoma, or lung cancer, or combinations thereof; optionally wherein the cancer or other malignancies, neoplasm, hyperplasia, hypertrophy, dysplasia and/or tumor angiogenesis in an animal comprises benign prostatic hyperplasia or molar pregnancy.
- 10. The method according to claim 1, wherein said nitric oxide mimetic comprises nitric oxide, a nitric oxide donor, a compound that generates or releases nitric oxide through biotransformation, a compound that generates nitric oxide spontaneously or spontaneously releases nitric oxide, or a compound which generates nitric oxide, or combinations thereof.
- 11. The method according to claim 10, wherein said nitric oxide mimetic is
(1) a nitric oxide donor selected from nitroglycerin (GTN), isosorbide 5-mononitrate (ISMN), isosorbide dinitrate (ISDN), pentaerythritol tetranitrate (PETN), erthrityl tetranitrate (ETN), N-hydroxyl-L-arginine (NOHA), N6-(1-iminoethyl)lysine) (L-NIL), L-N5-(1-iminoethyl) ornithine (LN-NIO), Nw-methyl-L-arginine (L-NMMA), S-nitrosogluthathione (SNOG), S,S-dinitrosodithiol (SSDD), [N-[2(nitroxyethyl)]-3-pyridinecarboxamide (nicorandil), sodium nitroprusside (SNP), S-nitroso-N-acetylpenicilamine (SNAP), 3-morpholino-sydnonimine (SIN-1), molsidomine, DEA-NONOate (2(N,N-diethylamino)-diazenolate-2-oxide), and spermine NONOate (N-[4-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino]butyl-1,3-propanediamine; (2) a compound that activates stages of NO pathway, a compound which enables or facilitates NO utilization by a cell, a compound which directly activates guanylyl cyclase, or a phosphodiesterase inhibitor, or combinations thereof, (3) a type I, II, III, IV or V phosphodiesterase inhibitor, or combinations thereof; or (4) a protein kinase G activator.
- 12. The method according to claim 4, wherein said antimalignant therapeutic agent includes radiation therapy, thermal therapy, immunotherapy, or chemotherapy, or combinations thereof, optionally wherein the antimalignant therapeutic modality comprises radiation therapy, and said nitric oxide mimetic is a nitric oxide, a nitric oxide donor, a compound that generates or releases nitric oxide through biotransformation, or a compound that generates nitric oxide spontaneously or spontaneously releases nitric oxide only in the presence of oxygen, or combinations thereof, wherein said nitric oxide mimetic is administered during the radiation therapy.
- 13. The method according to claim 12, wherein said chemotherapy comprises administration of chemotherapeutic agent that is an anti-angiogenic agent, an antimetabolite, an antibiotic, an endothelin activating agent, an enzyme inhibitor, a hormonal agent, ocreotide acetate, a microtubule-disruptor agent, a microtubule-stabilizing agent, a vinca alkaloid, a epipodophyllotoxin, a toposiomerase inhibitor; a prenyl-protein transferase inhibitor, hydroxyurea, procarbazine, mitotane, hexamethylmelamine, a platinum coordination complex, a biological response modifier, a growth factor, an immune modulator, or a monoclonal antibody, or a combination thereof.
- 14. The method according to claim 1, wherein the dose of nitric oxide mimetic is at least 3- to 10,000-fold lower, preferably 100-10,000 fold lower than a dose of nitric oxide mimetic that produces vasodilation.
- 15. The method according to claim 1, wherein said nitric oxide mimetic is a known vasodilatory compound and said mimetic is administered at a dose of at least 3- to 10,000-fold lower, preferably 100-10,000 fold lower than the dose of nitric oxide mimetic known to produce vasodilation.
- 16. The method according to claim 1, wherein said nitric oxide mimetic is selected from the group consisting of a calcium channel blocker, an α-adrenergic receptor antagonist, a β-adrenergic receptor agonist, a phosphodiesterase inhibitor, a cAMP-dependent protein kinase activator, a superoxide scavenger, a potassium channel activator, a benzodiazepine, an adrenergic nerve inhibitor, an antidiarrheal agent, a HMG-CoA reductase inhibitor, an adenosine receptor modulator, a adenylyl cyclase activator, an endothelin receptor antagonist, a bisphosphonate, a cGMP-dependent protein kinase activator, a guanylyl cyclase activator and a SOC inhibitor.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application Serial Nos. 60/362,969 filed Mar. 6, 2002, and 60/362,620 filed Mar. 7, 2002, and U.S. patent application Ser. No. 10/042,039, filed Oct. 25, 2001, which are herein incorporated by reference. U.S. patent application Ser. No. 10/042,039 is a continuation-in-part of U.S. application Ser. No. 09/842,547, filed Apr. 26, 2001, which claims the benefit of U.S. Provisional Application Nos. 60/277,469, filed Mar. 21, 2001, and 60/199,757, filed Apr. 26, 2000, which are herein incorporated by reference in their entirety.
Provisional Applications (4)
|
Number |
Date |
Country |
|
60362620 |
Mar 2002 |
US |
|
60362969 |
Mar 2002 |
US |
|
60277469 |
Mar 2001 |
US |
|
60199757 |
Apr 2000 |
US |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
10042039 |
Oct 2001 |
US |
Child |
10384499 |
Mar 2003 |
US |
Parent |
09842547 |
Apr 2001 |
US |
Child |
10384499 |
Mar 2003 |
US |