Nitric oxide is a key component in inflammation-accelerated tumorigenesis.

Nitric oxide (NO(*)), an important signaling molecule and a component of inflammatory response, is involved in tumorigenesis. However, the quantity of NO(*) and the cellular microenvironment influences the role of NO(*) in tumor development. We used a genetic strategy to test the hypothesis that an inflammatory microenvironment with an enhanced level of NO(*) accelerates spontaneous tumor development.

Nitric oxide, a mediator of inflammation, suppresses tumorigenesis.

Inflammation influences the development of cancer. The nitric oxide synthase (NOS2) is induced by inflammatory cytokines, e.g.

Cerebellar ataxia, seizures, premature death, and cardiac abnormalities in mice with targeted disruption of the Cacna2d2 gene.

CACNA2D2 is a putative tumor suppressor gene located in the human chromosome 3p21.3 region that shows frequent allelic imbalances in lung, breast, and other cancers. The alpha2delta-2 protein encoded by the gene is a regulatory subunit of voltage-dependent calcium channels and is expressed in brain, heart, and other tissues.

Bisimidazoacridones and related compounds: new antineoplastic agents with high selectivity against colon tumors.

A new class of potent and highly selective antitumor agents has been synthesized. Bisimidazoacridones, where the tetracyclic ring systems are held together by either a N2-methyldiethylenetriamine or 3,3'-diamino-N-methyldipropylamine linker, and related asymmetrical compounds, where one of the imidazoacridone ring system was replaced by a triazoloacridone ring system, were found to be cytostatic and cytotoxic in vitro. Some of these compounds, such as 5,5'-[(methylimino)bis(3,1-propanediylimino)]bis[6H-imidazo[ 4,5,1-de]acridin-6-one] (4b) showed remarkably high activity and selectivity for colon cancer in the National Cancer Institute screen.

Prevention of tumors in rats by cross-protective immunization.

F344 inbred were repeatedly immunized (days 0, 28, and 42) with normal syngeneic or allogeneic rat tissues or transplantable syngeneic or allogeneic rat tumors (some of which were virus producing). Immunized rats were challenged by sc injection of 10(5) or 10(6) syngeneic rat tumor cells from either of two different tumor lines. Successful cross-protective immunization prevented tumor development in rats that were challenged at 100-1,000 times the 50% tumor dose.