Arachidonic acid (AA), an important polyunsaturated fatty acid in the brain, is hydrolyzed by a direct action of phospholipase A2 (PLA2) or through the combined action of phospholipase C and diacylglycerol lipase, and released into the cytoplasm. Various derivatives of AA can be synthesized mainly through the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (P450) enzyme pathways. AA and its metabolic enzymes and metabolites play important roles in a variety of neurophysiological activities. The abnormal metabolites and their catalytic enzymes in the AA cascade are related to the pathogenesis of various central nervous system (CNS) diseases, including epilepsy. Here, we systematically reviewed literatures in PubMed about the latest randomized controlled trials, animal studies and clinical studies concerning the known features of AA, its metabolic enzymes and metabolites, and their roles in epilepsy. The exclusion criteria include non-original studies and articles not in English.

Laryngeal squamous cell carcinoma (LSCC) is the second most common cancer among head and neck cancers. Despite a lower incidence of laryngeal carcinoma, new diagnostic techniques, and more targeted therapies, the overall survival has not changed significantly in the last decades, leading to a negative prognosis in advanced stages. Recently, several studies have focused on the identification of biomarkers that may play a critical role in the pathogenesis of LSCC. Reviewing the literature on the main databases, this study aims to investigate the role of some biomarkers in LSCC that are correlated with oxidative stress and inflammation: heat shock proteins; metallothioneins; nuclear factor erythroid 2-related factor 2; heme oxygenase; cyclooxygenase-2; and micro ribonucleic acids. This review shows that biomarker expression depends on the type, grade of differentiation, stage, and site of carcinoma. In addition, the role of these biomarkers in LSCC is still little-known and little-studied. However, the study of biomarker expression and the detection of a possible correlation with patients\' epidemiological, clinicopathological, and therapeutics data may lead to better awareness and knowledge of the tumor, to the identification of the best therapeutic strategy, and the most proper follow-up protocol tailored for each patient. In conclusion, the achievement of these goals may improve the prognosis of LSCC patients.

OBJECTIVE: To assess the immunohistochemistry phenotype of cyclooxygenase-2 (COX-2) in breast cancer (BC) and to correlate it with histological and clinical prognostic factors.
METHODS: This retrospective study utilized COX-2 monoclonal antibody in an immunohistochemistry staining of tissue microarrays slides of 570 cases of previously diagnosed BC and with 52 of normal breast tissues from breast specimens resected for benign lesions or reconstruction (fibroadenoma and normal breast epithelium). This project was carried out in the Laboratory of pathology, King Abdulaziz University, Jeddah, Saudi Arabia, between September 2019 and September 2021.
RESULTS: The present data showed an important connection between the COX-2 expression phenotype and BC compared to benign breast tissues (p=0.034). The expression pattern of COX-2 was allied significantly with some factors which distinguished aggressive subtypes of BC, such as stage, distant metastases, lymphovascular invasion, and poor survival.
CONCLUSIONS: Cyclooxygenase-2 is a valuable marker that could facilitate BC diagnosis and prognosis.

The main objective of this systematic review is to investigate the expression level of the cyclooxygenase-2 (COX-2) in rectal cancer treated with either preoperative radiotherapy or radiochemotherapy. In addition, we have summarized the effects of preoperative treatment of rectal cancer with regards to the expression levels of COX-2. A systematic literature review was performed in The Cochrane Library, PubMed, Web of Science, and Scopus databases on 1 January 2021 with the usage of the following search string-(cyclooxygenase-2) OR (COX-2) AND (rectal cancer) AND (preoperative radiochemotherapy) OR (preoperative radiotherapy). Among the 176 included in the analysis, only 13 studies were included for data extraction with a total number of 2095 patients. The results of the analysis are based on the articles concerning the expression of COX-2 in rectal cancer among patients treated with preoperative radiotherapy or radiochemotherapy. A COX-2 expression is an early event involved in rectal cancer development. In cases of negative COX-2 expression, radiotherapy and radiochemotherapy might contribute to the reduction of a local recurrence. Therefore, COX-2 may be considered as a biologic factor while selecting patients for more effective, less time-consuming and less expensive preoperative treatment. However, the utility of the administration of COX-2 inhibitors to patients with COX-2 overexpression, in an attempt to improve the patients\' response rate to the neoadjuvant treatment, needs an assessment in further clinical trials.

This article presents a simplified view of celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) has, predominantly, two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role that is related to homeostatic effects in renal and platelets, while the latter is mainly responsible for induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and without side effects. To this end, of the generation of non-steroidal anti-inflammatory drugs from \"coxibs\", celecoxib is the only potent selective COX-2 inhibitor that is still commercially available. Thus, the compound celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for COX-2 enzyme. In this review, we provide highlights where such inhibition should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs) which act as COX-2 inhibitors with lesser side effects on the human body.

BACKGROUND: The roles of cyclooxygenase-2 (COX2) -765G > C (rs20417) and -1195G > A (rs689466) polymorphisms in gastric cancer were intensively analyzed, but the results of these studies were inconsistent. We conducted a meta-analysis and trial sequential analysis to elucidate the associations between these two COX2 polymorphisms and gastric cancer risk.
METHODS: Eligible studies were searched in PubMed, Embase, Cochrane library databases, China National Knowledge Infrastructure, Vip, and Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the genetic correlation between COX2 polymorphisms and gastric cancer susceptibility in five genetic models. Trial sequential analysis (TSA) was conducted to estimate whether the evidence of the results is sufficient. Furthermore, their interactions with Helicobacter pylori (H. pylori) or smoking in gastric cancer were also assessed using a case-only method.
RESULTS: The COX2 gene -765G > C polymorphism showed no significant association with gastric cancer susceptibility under all the five genetic models (take the allelic model for example: OR = 1.41, 95% CI: 0.95-2.09) in total analysis, and the stratification analysis by ethnicity indicated a similar association in Caucasian group under four genetic models (allelic model, dominant model, homozygous model, and heterozygous model). But in the subgroup of the Asian population, the -765G > C polymorphism was significantly associated with gastric cancer risk under the same contrast. The COX2 -1195G > A polymorphism showed significant correlation with gastric cancer susceptibility in total analysis, and stratification analysis by ethnicity also revealed a similar association in both Asian and Caucasian groups under the same contrast. Moreover, TSA confirmed such associations. Both H. pylori infection and cigarette smoking interacted with -765 C allele in gastric cancer (OR = 3.79, 95% CI: 1.15-12.43 and OR = 2.48, 95% CI: 1.38-4.48, respectively), but not in -1195 A allele (OR = 1.96, 95% CI: 0.62-6.21, and OR = 1.24, 95% CI: 0.93-1.64, respectively).
CONCLUSIONS: COX2 -765G > C polymorphism may serve as a genetic biomarker of gastric cancer in Asians, but not in Caucasians. COX2 -1195G > A polymorphism may serve as a genetic biomarker of gastric cancer in both Asians and Caucasians. The -765G > C, rather than -1195G > A polymorphism interacted with H. pylori infection or cigarette smoking to increase gastric cancer risk.

Regulatory T cells (Tregs) represent a low number of T-cell population under normal conditions, and they play key roles for maintaining immune system in homeostasis. The number of these cells is extensively increased in nearly all cancers, which is for dampening responses from immune system against cancer cells, metastasis, tumor recurrence, and treatment resistance. The interesting point is that apoptotic Tregs are stronger than their live counterparts for suppressing responses from immune system. Tregs within the tumor microenvironment have extensive positive cross-talks with other immunosuppressive cells including cancer-associated fibroblasts, cancer cells, macrophage type 2 cells, and myeloid-derived suppressor cells, and they have negative interactions with immunostimulatory cells including cytotoxic T lymphocytes (CTL) and natural killer cells. A wide variety of markers are expressed in Tregs, among them forkhead box P3 (FOXP3) is the most specific marker and the master regulator of these cells. Multiple signals are activated by Tregs including transforming growth factor-β, signal transducer and activator of transcription, and mTORC1. Treg reprogramming from an immunosuppressive to immunostimulatory proinflammatory phenotype is critical for increasing the efficacy of immunotherapy. This would be applicable through selective suppression of tumor-bearing receptors in Tregs, including FOXP3, programmed death-1, T-cell immunoglobulin mucin-3, and CTL-associated antigen-4, among others. Intratumoral Tregs can also be targeted by increasing the ratio for CTL/Treg.

Prostaglandins and thromboxane are lipid signaling molecules deriving from arachidonic acid by the action of the cyclooxygenase isoenzymes COX-1 and COX-2. The role of cyclooxygenases (particularly COX-2) and prostaglandins (particularly PGE₂) in cancer-related inflammation has been extensively investigated. In contrast, COX-1 has received less attention, although its expression increases in several human cancers and a pathogenetic role emerges from experimental models. COX-1 and COX-2 isoforms seem to operate in a coordinate manner in cancer pathophysiology, especially in the tumorigenesis process. However, in some cases, exemplified by the serous ovarian carcinoma, COX-1 plays a pivotal role, suggesting that other histopathological and molecular subtypes of cancer disease could share this feature. Importantly, the analysis of functional implications of COX-1-signaling, as well as of pharmacological action of COX-1-selective inhibitors, should not be restricted to the COX pathway and to the effects of prostaglandins already known for their ability of affecting the tumor phenotype. A knowledge-based choice of the most appropriate tumor cell models, and a major effort in investigating the COX-1 issue in the more general context of arachidonic acid metabolic network by using the systems biology approaches, should be strongly encouraged.

Accumulating evidence indicates an important pathophysiological role of brain inflammation in epilepsy. In this review, we will provide an update of specific inflammatory pathways that have been proposed to be crucial in the underlying molecular mechanisms of epilepsy, including the interleukin-1 receptor/toll-like receptor signalling, cyclooxygenase-2, tumour necrosis factor-alpha, complement signalling and chemokines. Furthermore, by drawing on evidence from preclinical and clinical studies we will discuss the potential of these signalling pathways targets for novel therapeutic interventions that control drug-resistant seizures or have disease-modifying effects. Finally, we will assess the use of these inflammatory pathways as potential biomarkers for the development of epilepsy or to measure the effectiveness of therapeutic interventions.

Cyclooxygenase-2 (COX-2) and its product prostaglandin E2 (PGE2) play a critical role in development and progression of colorectal cancer. Yet the detailed mechanistic pathways of COX-2 mediated signaling are still controversial and the role of COX-2 interaction in epithelial-stromal compartments on colorectal carcinogenesis is not well-understood either. In this review, we provide experimental evidence to support that (1) COX-2 signaling plays a major role in development and progression of colorectal cancer; (2) Stromal fibroblasts are a major source of COX-2 and PGE2; (3) Stromal-epithelial interaction mediated by COX-2 signaling promotes colorectal carcinogenesis and (4) Inhibition of stromal COX-2 signaling is necessary to control colorectal cancer. In conclusion, the evidences summarized in the review reflect recent advances and insight in mechanistic studies of colorectal cancer which can help the audiences to further understand the etiology and the control of this disease.