Duke University

North Carolina State University

Apex Bioscience, Inc.

Robert E Meyer

Joseph Bonaventura

Mark W Dewhirst

Joseph DeAngelo

The present invention is directed to the use of an inhibitor of NO activity, such as a nitric oxide scavenger or an NO synthase inhibitor, as as an adjunct to treatment of inappropriate tissue vascularization disorders.

Methods for improving therapeutic effectiveness of treatment of

The present invention is directed to the use of an inhibitor of NO activity, such as a nitric oxide scavenger or an NO synthase inhibitor, as an antitumor therapy to reduce tumor blood flow and oxygenation. The invention is also directed to administration of a nitric oxide scavenger or a nitric oxide synthase inhibitor to enhance the effectiveness of tumor therapy with hypoxic or acidic chemotherapeutic agents or hyperthermia. The invention is also directed to the administration of a nitric oxide synthase substrate to a subject previously administered a nitric oxide synthase inhibitor, in order to selectively inhibit tumor perfusion. In a specific example, administration of cell free hemoglobin, a nitric oxide scavenger, in conjunction with mitomycin C, a hypoxic cytotoxin, results in a significant delay in tumor growth of a human tumor xenograft in a mouse compared to mitomycin C alone. In another example, the administration of an inhibitor of nitric oxide synthase followed by the administration of a substrate of the enzyme causes a specific irreversible reduction of tumor blood flow, while normal blood flow is restored.

Methods for improving therapeutic effectiveness of agents for the

The present invention is directed to administration of a nitric oxide scavenger or a nitric oxide synthase inhibitor to enhance the effectiveness of tumor therapy with hypoxic or acidic chemotherapeutic agents or hyperthermia. In a specific example, administration of cell free hemoglobin, a nitric oxide scavenger, in conjunction with mitomycin C, a hypoxic cytotoxin, results in a significant delay in tumor growth of a human tumor xenograft in a mouse compared to mitomycin C alone.

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Cary, NC, United States of America

Robert E Meyer