@entity2 is the ultimate event resulting from a series of genetic and epigenetic alterations in the respiratory epithelium at risk. According to the "field @entity105 " theory, these alterations can occur throughout the entire lung. In individuals with a genetic predisposition combined with a sufficient amount of procarcinogenic environmental influences, a few of these sites may eventually progress to @entity5 . Recent advances in the understanding of @entity5 biology have identified new therapeutic targets for @entity2 chemoprevention, among which is @entity2247 . Ample preclinical data suggest that the @entity2247 / @entity1421 ( @entity1421 ) signaling pathway plays a pivotal role in conferring the malignant phenotype. Produced primarily by the action of COX on the free @entity1426 liberated from membrane phospholipids, overproduction of @entity1421 , which is predominantly generated by upregulation of @entity2247 , is associated with a variety of mechanisms known to facilitate tumorigenesis. These mechanisms include abnormal expression of epithelial growth factors, epithelial and microvascular proliferation, resistance to apoptosis, and suppression of antitumor immunity. The lung is one of the major sites of @entity1421 production, and previous studies have shown elevated @entity1421 levels in bronchoalveolar lavage fluid of @entity1 with @entity153 . In animal models, inhibition of @entity2247 and @entity1421 synthesis suppresses lung tumorigenesis. These preclinical data suggesting the antineoplastic effect of @entity2247 inhibitors provide the basis for several ongoing pilot clinical trials to determine the feasibility of @entity2247 inhibition in chemoprevention of @entity153 .

Chemoprevention strategies with cyclooxygenase-2 inhibitors for XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'malignancies'] @entity1421 :: ('MESH:D015232', 'Chemical') :: ['PGE2', 'prostaglandin E2'] @entity2 :: ('MESH:D008175', 'Disease') :: ['lung cancer', 'Clinical lung cancer'] @entity1426 :: ('MESH:D016718', 'Chemical') :: ['arachidonic acid'] @entity153 :: ('MESH:D002283', 'Disease') :: ['bronchogenic carcinoma'] @entity2247 :: ('4513', 'Gene') :: ['cyclooxgygenase (COX)-2', 'COX-2'] @entity105 :: ('MESH:D063646', 'Disease') :: ['carcinogenesis']
@entity2 :: (MESH:D008175,Disease) :: ['lung cancer']
