Blocking Stress Responses May Be Key to Better Cancer Surgery

Arachidonic acid (AA) metabolism has become a novel therapeutic target. Non-steroidal anti-inflammatory drugs (NSAIDs) were initially developed as anti-inflammatory agents for acute joint disorders, such as rheumatoid arthritis (RA), but paradoxically have been shown to increase the risk for MI and colitis during prophylactic long term treatment, unrelated to disease exacerbation. PGE2 is a major prostanoid mediator of tissue damage. More importantly, PGE2 also acts in concert with locally secreted cytokines and chemokines such as IL-6, IL-8, RANTES, MIP-1α/CCL3 and IP-10/CXCL10, to initiate and enhance the recruitment of host immune cells into inflamed tissues. Thus, strategies that block AA metabolism may be therapeutically sound for consideration in encouraging host defense against disease. Furthermore, intervention involving AMDs such as CYPs, COXs and thiolantioxidant group enzymes that mediate AA metabolites from the precursors such as AA, EPA, DHA leading to the production of PG and TXA2. This article provides an overview of the evolving concepts surrounding these exciting assays, emphasizing the unique role of NSAIDs acting by both inhibiting PG synthesis and fast and reverse cyclooxygenase enzyme activities in suppressing any further degree of ARDS, sepsis, AKI that would warrant clinical utility. Due to NSAIDs' ability to inhibit THI synthesis inhibitor as well as COX1 and COX2 pathways during pro-inflammatory phases, results of mounting studies strongly suggest that current NSAIDs and synthetic COX-2 inhibitors had utilized the "one drug—two SD" epoch while reference was made to adverse drug-induced liver, cardiac, renal, gastrointestinal, hematological toxicities leading to loss of investors and embracement for lower incidence of macular degeneration and neurological damage, which increases the likelihood of overdose effect; leading to further concerns with regards to drug reproducibility and developments, the growing regulatory forces and public perception.