Selective COX-2 inhibitors: A review of their therapeutic potential and safety in dentistry

COX-2 inhibition seems to balance the type-1/type-2 immune response, possibly via inhibition of prostaglandin E2. COX-2 inhibition reduces proinflammatory cytokines. COX-2 inhibition has an impact to the glutamatergic neurotransmission and influences the tryptophan/kynurenine metabolism: all three components seem to be involved in the pathophysiology of psychiatric disorders, particularly in schizophrenia and major depression.Due to the increase of proinflammatory cytokines and PGE2 in depressed patients, antiinflammatory treatment would be expected to show antidepressant effects. An antidepressant effect of rofecoxib was found in patients with osteoarthritis. An own randomized double blind pilot add-on study using the selective COX-2 inhibitor celecoxib in MD showed a significant therapeutic effect of the COX-2 inhibitor on depressive symptoms. Although those preliminary data have to be interpreted cautiously, those results are encouraging for further studies dealing with the inflammatory hypothesis of depression.Secondly, we and other research-groups performed several studies of COX-2 inhibitors in schizophrenia. In a prospective, randomized, double-blind study with the COX-2 inhibitor celecoxib in acute exacerbation of schizophrenia, a therapeutic effect of celecoxib was observed. The finding of a clinical advantage of COX-2 inhibition could not be replicated in a second study. Further analysis of the data revealed that the efficacy of therapy with a COX-2 inhibitor seems most pronounced in the first years of the schizophrenic disease process.It has to be considered, however, that therapy with COX-2 inhibitors is currently under discussion - as therapy with other non-steroidal antiphlogistics - due to cardiovascular side-effects.

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Therapeutic potential of COX-2 inhibitors in arthritis

Expert Opinion on Investigational Drugs ◽

10.1517/13543784.10.7.1317 ◽

2001 ◽

Vol 10 (7) ◽

pp. 1317-1325 ◽

Cited By ~ 3

Author(s):

Christopher G Jackson

Keyword(s):

Therapeutic Potential ◽

Cox 2 ◽

Cox 2 Inhibitors

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Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma

Journal of Experimental Medicine ◽

10.1084/jem.20050715 ◽

2005 ◽

Vol 202 (7) ◽

pp. 931-939 ◽

Cited By ~ 372

Author(s):

Paulo C. Rodriguez ◽

Claudia P. Hernandez ◽

David Quiceno ◽

Steven M. Dubinett ◽

Jovanny Zabaleta ◽

...

Keyword(s):

T Cell ◽

Lung Carcinoma ◽

Therapeutic Potential ◽

Suppressor Cells ◽

Myeloid Suppressor Cells ◽

Cox 2 ◽

Cancer Immunotherapies ◽

Cox 2 Inhibitors ◽

Arginase I ◽

Cox 1

Myeloid suppressor cells (MSCs) producing high levels of arginase I block T cell function by depleting l-arginine in cancer, chronic infections, and trauma patients. In cancer, MSCs infiltrating tumors and in circulation are an important mechanism for tumor evasion and impair the therapeutic potential of cancer immunotherapies. However, the mechanisms that induce arginase I in MSCs in cancer are unknown. Using the 3LL mouse lung carcinoma, we aimed to characterize these mechanisms. Arginase I expression was independent of T cell–produced cytokines. Instead, tumor-derived soluble factors resistant to proteases induced and maintained arginase I expression in MSCs. 3LL tumor cells constitutively express cyclooxygenase (COX)-1 and COX-2 and produce high levels of PGE2. Genetic and pharmacological inhibition of COX-2, but not COX-1, blocked arginase I induction in vitro and in vivo. Signaling through the PGE2 receptor E-prostanoid 4 expressed in MSCs induced arginase I. Furthermore, blocking arginase I expression using COX-2 inhibitors elicited a lymphocyte-mediated antitumor response. These results demonstrate a new pathway of prostaglandin-induced immune dysfunction and provide a novel mechanism that can help explain the cancer prevention effects of COX-2 inhibitors. Furthermore, an addition of arginase I represents a clinical approach to enhance the therapeutic potential of cancer immunotherapies.

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Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20246254 ◽

2019 ◽

Vol 20 (24) ◽

pp. 6254 ◽

Cited By ~ 11

Author(s):

Rei Mizuno ◽

Kenji Kawada ◽

Yoshiharu Sakai

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Prostaglandin E2 ◽

Therapeutic Potential ◽

Inflammatory Cells ◽

Promising Therapeutic Approach ◽

Ep Receptor ◽

Current Therapies ◽

Cox 2 ◽

Cox 2 Inhibitors

The number of colorectal cancer (CRC) patients is increasing worldwide. Accumulating evidence has shown that the tumor microenvironment (TME), including macrophages, neutrophils, and fibroblasts, plays an important role in the development and progression of CRC. Although targeting the TME could be a promising therapeutic approach, the mechanisms by which inflammatory cells promote CRC tumorigenesis are not well understood. When inflammation occurs in tissues, prostaglandin E2 (PGE2) is generated from arachidonic acid by the enzyme cyclooxygenase-2 (COX-2). PGE2 regulates multiple functions in various immune cells by binding to the downstream receptors EP1, EP2, EP3, and EP4, and plays an important role in the development of CRC. The current therapies targeting PGE2 using non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors have failed due to the global prostanoid suppression resulting in the severe adverse effects despite the fact they could prevent tumorigenesis. Therefore, therapies targeting the specific downstream molecules of PGE2 signaling could be a promising approach. This review highlights the role of each EP receptor in the TME of CRC tumorigenesis and their therapeutic potential.

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Neurobiology and Therapeutic Potential of Cyclooxygenase-2 (COX-2) Inhibitors for Inflammation in Neuropsychiatric Disorders

Frontiers in Psychiatry ◽

10.3389/fpsyt.2019.00605 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 11

Author(s):

Rickinder Sethi ◽

Nieves Gómez-Coronado ◽

Adam J. Walker ◽

Oliver D’Arcy Robertson ◽

Bruno Agustini ◽

...

Keyword(s):

Therapeutic Potential ◽

Neuropsychiatric Disorders ◽

Cyclooxygenase 2 ◽

Cox 2 ◽

Cox 2 Inhibitors

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Anti-inflammatory drugs with therapeutic effects and drug regulators

Himalayan Journal of Health Sciences ◽

10.22270/hjhs.v6i3.106 ◽

2021 ◽

pp. 30-39

Author(s):

Prateek Paul ◽

Manvi .

Keyword(s):

Therapeutic Potential ◽

Therapeutic Effects ◽

Negative Effects ◽

Naturally Occurring ◽

Anti Cancer ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors ◽

Cox 1

For prostaglandin production, the enzyme cyclooxygenase (COX) is required. The two COX isoforms are constitutive COX-1 (which is responsible for physiological functions) and inducible COX-2 (involved in inflammation). COX inhibition explains both the medicinal (inhibition of COX-2) and negative effects (inhibition of COX-1) effects of non-steroidal anti-inflammatory medicines (NSAIDs). Nonsteroidal anti-inflammatory medicines (NSAIDs) act by blocking the enzyme cyclooxygenase (COX), which produces prostaglandins (PGs). To a greater or lesser extent, they share similar side effects, such as stomach and renal toxicity. According to a recent study, there are at least two COX isoenzymes. COX-1 is a naturally occurring enzyme that creates prostaglandins (PGs), which protect the stomach and kidneys. Aspirin's well-known anti-cancer impact could also be related to its influence on COX-2, which is expressed in this condition. As a result, selective COX-2 inhibitors may have new therapeutic potential as anticancer drugs, as well as in preventing premature labor and maybe reducing the progression of Alzheimer's disease.

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