Positive Cyclooxygenase-2 Research Articles

Clinical relevance of cyclooxygenase 2 and vascular endothelial growth factor-A expression in classical Hodgkin lymphoma

Abstract Background Classical Hodgkin lymphoma (cHL) is a clonal lymphoid neoplasm derived from B cells. Cyclooxygenase 2 (COX2) and vascular endothelial growth factor-A (VEGF-A) play major roles in angiogenesis and impact cHL prognosis. Aim To measure COX2 and VEGF-A expression in cHL patients and assess their potential association with other laboratory and clinical parameters. Patients and methods Seventy-six cHL bone marrow (BM) biopsy specimens were histopathologically examined and immunohistochemically stained for COX2 and VEGF-A expression. Correlations between COX2 and VEGF-A expression and clinicopathologic factors were evaluated. Results COX2 and VEGF-A were expressed in 67/76 (88.2%) and 48/76 (63.2%) of BM specimens, respectively. VEGF-A was associated with advanced cHL stage (P=0.044) and BM infiltration confirmed by CD30 positivity (P=0.023). A significant association was found between VEGF-A positivity and mediastinal lymphadenopathy (P=0.049), inguinal lymphadenopathy (P=0.046), and pulmonary nodules (P=0.048). COX2 positivity was significantly associated with cervical lymphadenopathy (P=0.011). A positive association was found between expression of both markers (COX2 and VEGF-A) (P=0.001). Coexpression of COX2 and VEGF-A was associated with disease staging (P=0.016), mediastinal lymphadenopathy (P=0.019), and inguinal lymphadenopathy (P=0.044). Conclusion COX2 and VEGF-A, as major players in angiogenesis, are associated with tumor progression in cHL. These findings support targeting both markers as the potential therapeutic approach in cHL.

Expression and correlation of COX-2 and NUCB1 in colorectal adenocarcinoma.

To investigate the expression and correlation of COX-2 and NUCB1 in colorectal adenocarcinoma and adjacent tissues. The expression of COX-2 and NUCB1 and their effects on prognosis were predicted using bioinformatics. Immunohistochemistry was used to identify the expression of two molecules in 56 cases of colorectal adenocarcinoma and the surrounding tissues. The expression of two molecules and their association with clinicopathological variables were examined using the chi-square test. The association between COX-2 and NUCB1 was investigated using the Spearman correlation test. The STRING database revealed that COX-2 and NUCB1 were strongly linked. According to the UALCAN and HPA database, COX-2 was upregulated while NUCB1 was downregulated in colorectal adenocarcinoma, both at the protein and gene levels. The OS times for COX-2 and NUCB1 high expression, however, exhibited the same patterns. The rate of positive COX-2 immunohistochemical staining in cancer tissues was 69.64% (39/56), which was significantly higher than the rate in healthy tissues 28.57% (16/56). NUCB1 was expressed positively in cancer tissues at a rate of 64.29% (36/56) compared to just 19.64% (11/56) in neighboring tissues. The positive expression levels of COX-2 and NUCB1 were both closely related to clinical stage, differentiation degree, and lymphatic metastases (P < 0.05). In colorectal cancer, COX-2 and NUCB1 expression were significantly correlated (rs = 0.6312, P < 0.001). Both COX-2 and NUCB1 are overexpressed and significantly associated in colorectal adenocarcinoma.

Molecular Targets and Mechanisms of 6,7-Dihydroxy-2,4-dimethoxyphenanthrene from Chinese Yam Modulating NF-κB/COX-2 Signaling Pathway: The Application of Molecular Docking and Gene Silencing

Chinese yam (Dioscorea opposita) tuber has a significant effect of invigorating the intestine and improving the symptoms of long-term diarrhea according to the records of the Chinese Pharmacopoeia. Phenanthrene polyphenols from Chinese yam, with higher inhibition of cyclooxygenase-2 (COX-2) than anti-inflammatory drugs, are an important material basis in alleviating ulcerative colitis via nuclear factor kappa-B (NF-κB)/COX-2 pathway, based on our previous research. The present study further explored the target and molecular mechanisms of phenanthrenes' modulation of the NF-κB/COX-2 signaling pathway by means of molecular docking and gene silencing. Firstly, interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) expression of 6-hydroxy-2,4,7-trimethoxyphenanthrene (PC2)/6,7-dihydroxy-2,4-dimethoxyphe-nanthrene (PC4) were compared on TNF-α induced human colon adenocarcinoma (Caco-2) cells. Secondly, molecular docking and dynamics simulation were implemented for PC2/PC4 and COX-2. Finally, COX-2 silencing was performed on TNF-α induced Caco-2 cells to confirm the target of PC4 on NF-κB/COX-2 pathway. Lower expression of IL-8 and TNF-α in PC4 treated Caco-2 cells indicated that PC4 had stronger anti-inflammatory activity than PC2. The binding of PC4 and COX-2 was stronger due to the hydrogen bond between hydroxyl group and Tyr385. No significant differences were found in phosphorylation nuclear factor kappa-B inhibitor alpha (pIkBα), phosphorylation NF-κB (pNF-κB) and phosphorylation extracellular signal-regulated kinase 1/2 (pERK1/2) expression between control and PC4 group after silencing, while these protein expressions significantly decreased in PC4 group without silencing, which confirmed that COX-2 was the important target for PC4 in alleviating ulcerative colitis. These findings indicate that PC4 was supposed to have inhibited NF-κB pathway mediated inflammation via suppression of positive feedback targeting COX-2.

Relationships of BRAF V600E Gene Mutation With Some Immunohistochemical Markers and Recurrence Rate in Patients With Thyroid Carcinoma.

The B-type rafkinase (BRAF) V600E gene mutation plays an important role in the pathogenesis, diagnosis, and prognosis of thyroid carcinoma. This study was conducted to investigate the rate of the BRAF V600E mutation, the relationships between the BRAF V600E gene mutation and some immunohistochemical markers, and recurrence rate in patients with differentiated thyroid cancer. The study was conducted by a descriptive and longitudinal follow-up method on 102 thyroid carcinoma patients at 103 Military Hospital, Hanoi, Vietnam. All patients were identified with the BRAF V600E gene mutation by real-time polymerase chain reaction. The rate of BRAF V600E gene mutation in patients with thyroid cancer was 60.8%. Patients with BRAF V600E gene mutation had a significantly higher rate of positive cyclooxygenase 2 (COX-2) and Ki67 markers than those without the mutation (COX-2: odds ratio [OR] = 2.93; 95% confidence interval [CI] = 1.27-6.74, P = .011; Ki67: OR = 3.41; 95% CI = 1.31-8.88, P = .01). A statistically significant relationship was identified between the rate of BRAF V600E mutation and the rate of positive Hector Battifora mesothelial 1 (HBME-1) (B = -1.040; P = .037) and COX-2 (B = -1.123; P = .023) markers. The recurrence rate in patients with BRAF V600E gene mutation was significantly higher than that in those without the mutation (P = .007). The mean of the recurrence time of patients with BRAF V600E mutation was significantly lower than that in those without the mutation (P = .011). A high prevalence of BRAF V600E gene mutation was found in thyroid carcinoma patients. The rates of positive HBME-1, COX-2, and Ki67 markers were significantly correlated to BRAF V600E gene mutation. Patients with BRAF V600E gene mutation showed a significantly higher relapse rate and earlier relapse time than those without the mutation.

Ulipristal Asetatın Ratlarda Oluşturulan Cerrahi Endometriozise Etkisi

Objective: The effect of Ulipristal Acetate on endometriosis foci created in rats was investigated. Methods: The study was conducted with 12-week-old rats weighing approximately 280 grams. After creating an autologous endometriosis model, the group that did not receive ulipristal acetate negative was administered with oral saline daily, and the group given ulipristal acetate positive was administered with 0.5 mg/kg (0.125 mg/rat/day) orally for 4 weeks. Ectopic endometrial tissues were removed for histopathological and immunohistochemical evaluations. Staining was performed with Hematoxylin Eosin, Ki-67, and Cyclooxygenase-2. Results: The Hematoxylin-Eosin Staining score of the ectopic endometrium surface epithelium was found to be 2.5 points in the ulipristal acetate negative group, and 0.5 points in the ulipristal acetate positive group. In the immunohistochemical evaluation, Ki-67 positivity of the ectopic endometrial surface epithelium was found to be 71.2% in the ulipristal acetate negative group vs. 31.7% in the ulipristal acetate positive group. Cyclooxygenase-2 positivity was detected as 67% in the ulipristal acetate negative group vs. 27% in the ulipristal acetate positive group. Conclusions: Hematoxylin-Eosin staining revealed that ulipristal acetate negative group was 2.5 (well-moderately preserved epithelium), and the ulipristal acetate positive group was 0.5 (epithelium was rarely present or absent). It was found that the percentage of Ki-67 and Cyclooxygenase-2 immunohistochemical positivity was decreased in the ulipristal acetate positive group compared to the ulipristal acetate negative group at a statistically significant level. More literature data are needed on this subject.

Cyclooxygenase-2 (COX-2) Expression in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma: An Immunohistochemical Study.

Introduction:Growing evidence has shown that cyclooxygenase-2 (COX-2), an enzyme capable of catalyzing prostaglandin production, plays a key role in carcinogenesis. Selective COX-2 inhibitors have been shown to reduce the establishment of tumors such as oral squamous cell carcinoma (OSCC) and premalignant conditions such oral submucous fibrosis (OSMF) in experimental models. The aim of this study was to investigate the immunohistochemical expression of COX-2 in OSCC and OSMF with the normal oral mucosa as control.Material and Methods:Forty-five formalin-fixed paraffin-embedded samples comprising 20 OSCC, 20 OSMF, and 5 normal oral mucosa specimens were withdrawn from the archives of the Department of Oral and Maxillofacial Pathology for immunohistochemical examination for COX-2 expression. Negative and less than 5% COX-2 positivity was considered negative expressions, while greater than or equal to 5% COX-2 positivity was considered positive expression. The data obtained were statistically analyzed.Results:The difference in percentages of expression in normal mucosa, OSCC, and OSMF was highly significant (P < 0.01). In comparison to normal mucosa, OSCC and OSMF had an increased level of COX-2 expression. However, there was an insignificant difference between the various histological gradings of OSCC and OSMF.Conclusion:The results of the present study confirm the role of COX-2 in carcinogenesis and in the progression of premalignant conditions to malignancy.

Colonic mucosal eosinophilia and immunohistochemical expression of COX-2 and NF-kB in patients with irritable bowel syndrome.

There is growing evidence that eosinophilic infiltration can release mediators which are harmful to the intestinal epithelium in patients with irritable bowel syndrome (IBS). Although cyclooxygenase 2 (COX-2) and nuclear factor-kappa beta (NF-kB) expression had been previously reported to increase in many inflammatory conditions, there is a paucity in data investigating their expressions in IBS. Our aim was to evaluate colonic mucosal eosinophilia and immunohistochemical expression of COX-2 and NF-kB in patients with irritable bowel syndrome. A total of 80 patients who met the inclusion criteria of IBS based on Rome IV symptoms questionnaire were subjected to abdominal ultrasound, laboratory investigations, serum immunoglobulin E (IgE) level assessment and colonoscopic examination. Immunohistochemistry was performed to detect COX-2 and NF-kB expression in colonic biopsies obtained from IBS patients. Histopathological examination showed that 60 colonic biopsy specimens (75%) showed few mixed inflammatory cells ≤3 cells/ HPF, 12 biopsy specimens (15%) showed eosinophilic infiltration ≥25 eosinophils/HPF and 8 biopsy specimens (10%) showed severe lymphocytic infiltration and aggregation. Colonic eosinophilic infiltrate was significantly higher among patients presented with IBS-D subtype. Serum IgE was significantly higher among patients with colonic eosinophilic infiltrate than the others. In IBS-D patients, colonic mucosa showed positive expression of COX-2 and NF-kB in 52.1% and 81.25% of cases, respectively. Patients with IBS -particularly IBS-D subtype- should undergo colonoscopy and biopsy to exclude underlying inflammatory pathology. Moreover, patients with positive COX-2 and NF-kB need further evaluation and follow-up.

ω-3 and ω-6 Polyunsaturated Fatty Acids Regulate the Proliferation, Invasion and Angiogenesis of Gastric Cancer Through COX/PGE Signaling Pathway.

BackgroundThis study aims to investigate the effects of ω-3, ω-6 polyunsaturated fatty acids (PUFAs), and their middle metabolites prostaglandin (PGE)2 and PGE3 on proliferation, invasion, and angiogenesis formation of gastric cancer cells and to explore associated mechanism.MethodsRT-PCR and ELISA were used to detect the expression of cyclooxygenase (COX)-1 and COX-2 in gastric cancer cell lines. The effect of ω-3, ω-6, PGE2, and PGE3 on the proliferation, invasion, and angiogenesis of gastric cancer cells were measured by cell proliferation, invasion, and angiogenesis assay in vitro. COX-2 small interfering RNA (siRNA) was transfected into gastric cancer cells, and the expression of COX-2 protein was detected by Western blot. COX-2 gene silencing influencing proliferation, invasion, and angiogenesis potential of gastric cancer cells was detected by WST-1, transwell chamber, and angiogenesis assay, respectively.ResultsCOX-2 was only expressed in MKN74 and MKN45 cells. In gastric cancer cell lines with positive COX-2 expression, ω-6 and PGE2 could significantly enhance the proliferation, invasion, and angiogenesis of gastric cancer cells, and after transfection with COX-2 siRNA, the effects of ω-6 and PGE2 on enhancing the proliferation, invasion, and angiogenesis of gastric cancer cells were significantly attenuated; ω-3 and PEG3 could inhibit the proliferation, invasion, and angiogenesis of gastric cancer cells. In gastric cancer cell lines with negative COX-2 expression, ω-6 and PGE2 had no significant effect on the proliferation, invasion, and angiogenesis of gastric cancer; ω-3 and PGE3 could significantly inhibit the proliferation, invasion, and angiogenesis of gastric cancer.Conclusionω-6 PUFAs reinforce the metastatic potential of gastric cancer cells via COX-2/PGE2; ω-3 PUFAs inhibit the metastatic potential of gastric cancer via COX-1/PGE3 signaling axis.

Expression and prognostic significance of cyclin D1 and cyclooxygenase-2 in colorectal carcinoma

Background Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Cyclin D1 (CNND1) and cyclooxygenase-2 (Cox-2) are expressed in a plethora of neoplastic tissues. Aim The present work was conducted to examine the immunohistochemical expression of CNND1 and Cox-2 in colorectal adenocarcinoma, compared with colonic adenoma to evaluate its association with various clinicopathological features. Patients and methods A total of 30 colorectal adenocarcinoma cases, 20 cases of colonic adenoma, and 10 normal colonic mucosal biopsies as controls were studied. Immunohistochemical technique was applied to detect CNND1 and Cox-2 expression and correlate them with clinicopathological findings. Results Both cytoplasmic high CNND1 and nuclear positive Cox-2 expression were significantly increased from normal colonic mucosa (0 and 10%, respectively) to CRC (80 and 83.3%, respectively) passing through colon adenoma (25 and 55%, respectively) (P≤0.001 for both). High CNND1 score was significantly related to lymph node spread and stage (P≤0.001 for both). A statistically significant difference was documented between Cox-2 and grade of differentiation (P=0.017), distant metastasis, and TNM stage (P=0.033, 0.003, respectively). Conclusion The present work suggests the oncogenic role of CNND1 and Cox-2 in CRC. Furthermore, overexpressions of CNND1 and Cox-2 are associated with poor prognostic factors, implicating their potentially prognostic role in CRC.

The Upregulation of COX2 in Human Degenerated Nucleus Pulposus: The Association of Inflammation with Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is an important risk factor of low back pain. We previously found upregulated markers of fibrosis, the late stage of chronic inflammation, in degenerated IVD with a small number of clinical specimens. Here, we aimed to study on a larger scale the association of cyclooxygenase 2 (COX2), an inflammation and/or pain marker, with IVDD. This study involved 107 LBP participants. The IVD degeneration level was graded on a 1–5 scale according to the Pfirrmann classification system. Discs at grades 1-3 were further grouped as white discs with grades 4-5 as black discs. We recorded baseline information about age, gender, body mass index (BMI), diabetes history, smoking history, and magnetic resonance imaging (MRI). Their association with IVDD was statistically analyzed. The expression level of COX2 was investigated by immunohistochemistry. The total integrated COX2 optical density (IOD), number of COX2-positive cells, and total cell number of each image were counted and analyzed by Image-Pro Plus software. The IOD and number of COX2-positive cells were divided by the total cell number to obtain COX2 expression density (IOD/cell) and COX2 positivity (cell+/cell). As a result, among the baseline information investigated, only age was found to have a significant association with IVDD. The IOD/cell was found to be significantly increased from grade 2 to grade 5, as well as in black discs compared to white discs. The cell+/cell displayed the same trend that it increased in highly degenerative discs compared to their counterparts. In conclusion, the expression of COX2 is associated with IVDD, which highlights COX2 as a biomarker for IVD degeneration and indicates the involvement of inflammation and pain signaling in IVDD.

A positive COX-2/IL-1β loop promotes decidualization by upregulating CD82.

A successful pregnancy requires sufficient decidualization of endometrial stromal cells (ESCs). CD82, a metastasis suppressor, is a critical regulator for trophoblast invasion but the effect in decidualization was largely unknown. Here we reported that there was a high level of CD82 in DSC by the immunohistochemistry staining and flow cytometer analysis. Stimulation with prostaglandin E2 (PGE2) elevated the expression of CD82 in ESCs. In contrast, celecoxib, a selective COX-2 inhibitor, significantly downregulated the expression of CD82 in decidual stromal cells (DSCs). Bioinformatics analysis and further research showed that recombinant human interleukin (IL)-1β protein (rhIL-1β) upregulated CD82 in ESCs. Of note, blocking IL-1β signaling with anti-human IL-1β neutralizing antibody could reverse the stimulatory effect of PGE2 on CD82 in ESCs. Silencing CD82 resulted in the decease of the decidualization markers PRL and IGFBP1 mRNA levels in DSCs. More importantly, we observed rhIL-1β also upregulated the expression of COX-2, and the upregulation of PRL and IGFBP1 induced by rhIL-1β could be abolished by celecoxib in ESCs or CD82 deficiency in DSCs. This study suggests that CD82 should be a novel promotor for decidualization under a positive regulation of the COX-2/PGE2/IL-1β positive feedback loop.

Cyclooxygenase-2 expression in colorectal carcinoma, adenomatous polyps and non-tumour bearing margins of resection tissues in a cohort of black Africans.

BackgroundEmerging data suggest a negative role of cyclooxygenase-2 (COX-2) in colorectal carcinomas (CRC). Investigating this in developing communities such as ours helps to contribute to existing understanding of these lesions.Methods and findingsFormalin-fixed paraffin-embedded CRC colectomy tissues and their corresponding non-tumour margins of resected tissues were sectioned and stained with COX-2 antibody. Adenomatous polyp tissues from non-cancer bearing individuals were similarly processed for comparison. COX-2 expression was scored for percentage (< 5% = 0; 6%-25% = 1; 26%-50% = 2; 51%-75% = 3; 76%-100% = 4) and intensity (no staining = 0; yellow = 2; yellowish-brown = 3, brown = 4). Total immunoscore (percentage + intensity score) ≥ 2 was regarded as positive COX-2 expression. Outcome was statistically evaluated with clinicopathological data to determine COX-2 expression-associated and predictor variables. Ninety-five CRC cases and 27 matched non-tumour tissues as well as 31 adenomatous polyps met the inclusion criteria. Individuals with CRC had a mean age of 56.1 ± 12.6 years while those with adenomatous polyps had a median age of 65 years (range 43–88). COX-2 was differentially overexpressed in CRCs (69/95; 72.6%) and in adenomatous polyps (17/31; 54.8%) than in non-tumour tissues 5/27 (18.5%); p < 0.001). The difference in COX-2 expression between CRC and polyps was non-significant (p > 0.065). Tumour grade, advanced pT-stage, tumour-infiltrating lymphocytes, and dirty necrosis were also significantly associated with COX-2 expression (p < 0.035; 0.043, 0.035 and 0.004, respectively). Only dirty necrosis and Crohns-like lymphocytic aggregates predicted COX-2 expression (p < 0.05).ConclusionThis study showed a progressive increase in COX-2 expression from normal to adenomatous polyp and CRC tissues, this being associated with poorer prognostic indicators. Although COX-2 appears early in CRC, it may play a secondary role in promoting tumour growth and invasiveness.

Importance of COX-2 expression in Wilms' tumour: A preliminary study.

In Wilms' tumour (WT), secondary malignancies caused by the side effects of intensive treatments remain one of the important problems. Therefore, there is a need for new studies to identify low- and high-risk groups for WT and to improve the treatment regimens of children in the low-risk group. In our study, we aimed to determine the prognostic significance of the cyclooxygenase-2 (COX-2) biomarker in WT. Our study included 24 patients diagnosed with WT between January 2010 and December 2019. The correlation between COX-2 expression and significant prognostic parameters was investigated by studying the COX-2 antibody using the immunohistochemical method. COX-2 expression was observed in 22 of the patients and it was more evident in the epithelial component. No significant correlation was observed between COX-2 positivity and prognostic parameters. There was also no statistically significant difference between the two groups regarding survival (P=.563). In our study, no significant relationship was found between significant prognostic parameters and COX-2 expression. Since COX-2 expression was observed in almost all patients, we consider that the COX-2 pathway is effective during the development phase of WT.

Radiosynthesis and evaluation of [18F]FMTP, a COX-2 PET ligand.

The upregulation of cyclooxygenase-2 (COX-2) is involved in neuroinflammation associated with many neurological diseases as well as cancers of the brain. Outside the brain, inflammation and COX-2 induction contribute to the pathogenesis of pain, arthritis, acute allograft rejection, and in response to infections, tumors, autoimmune disorders, and injuries. Herein, we report the radiochemical synthesis and evaluation of [18F]6-fluoro-2-(4-(methylsulfonyl)phenyl)-N-(thiophen-2-ylmethyl)pyrimidin-4-amine ([18F]FMTP), a high-affinity COX-2 inhibitor, by cell uptake and PET imaging studies. The radiochemical synthesis of [18F]FMTP was optimized using chlorine to fluorine displacement method, by reacting [18F]fluoride/K222/K2CO3 with the precursor molecule. Cellular uptake studies of [18F]FMTP was performed in COX-2 positive BxPC3 and COX-2 negative PANC-1 cell lines with unlabeled FMTP as well as celecoxib to define specific binding agents. Dynamic microPET image acquisitionwas performed in anesthetized nude mice (n = 3), lipopolysaccharide (LPS) induced neuroinflammation mice (n = 4), and phosphate-buffered saline (PBS) administered control mice (n = 4) using a Trifoil microPET/CT for a scan period of 60min. A twofold higher binding of [18F]FMTP was found in COX-2 positive BxPC3 cells compared with COX-2 negative PANC-1 cells. The radioligand did not show specific binding to COX-2 negative PANC-1 cells. MicroPET imaging in wild-type mice indicated blood-brain barrier (BBB) penetration and fast washout of [18F]FMTP in the brain, likely due to the low constitutive COX-2 expression in the normal brain. In contrast, a ~ twofold higher uptake of the radioligand was found in LPS-induced mice brain than PBS treated control mice. Specific binding to COX-2 in BxPC3 cell lines, BBB permeability, and increased brain uptake in neuroinflammation mice qualifies [18F]FMTP as a potential PET tracer for studying inflammation.

PET measurement of cyclooxygenase-2 using a novel radioligand: upregulation in primate neuroinflammation and first-in-human study

BackgroundCyclooxygenase-2 (COX-2), which is rapidly upregulated by inflammation, is a key enzyme catalyzing the rate-limiting step in the synthesis of several inflammatory prostanoids. Successful positron emission tomography (PET) radioligand imaging of COX-2 in vivo could be a potentially powerful tool for assessing inflammatory response in the brain and periphery. To date, however, the development of PET radioligands for COX-2 has had limited success.MethodsThe novel PET tracer [11C]MC1 was used to examine COX-2 expression [1] in the brains of four rhesus macaques at baseline and after injection of the inflammogen lipopolysaccharide (LPS) into the right putamen, and [2] in the joints of two human participants with rheumatoid arthritis and two healthy individuals. In the primate study, two monkeys had one LPS injection, and two monkeys had a second injection 33 and 44 days, respectively, after the first LPS injection. As a comparator, COX-1 expression was measured using [11C]PS13.ResultsCOX-2 binding, expressed as the ratio of specific to nondisplaceable uptake (BPND) of [11C]MC1, increased on day 1 post-LPS injection; no such increase in COX-1 expression, measured using [11C]PS13, was observed. The day after the second LPS injection, a brain lesion (~ 0.5 cm in diameter) with high COX-2 density and high BPND (1.8) was observed. Postmortem brain analysis at the gene transcript or protein level confirmed in vivo PET results. An incidental finding in an unrelated monkey found a line of COX-2 positivity along an incision in skull muscle, demonstrating that [11C]MC1 can localize inflammation peripheral to the brain. In patients with rheumatoid arthritis, [11C]MC1 successfully imaged upregulated COX-2 in the arthritic hand and shoulder and apparently in the brain. Uptake was blocked by celecoxib, a COX-2 preferential inhibitor.ConclusionsTaken together, these results indicate that [11C]MC1 can image and quantify COX-2 upregulation in both monkey brain after LPS-induced neuroinflammation and in human peripheral tissue with inflammation.Trial registrationClinicalTrials.gov NCT03912428. Registered April 11, 2019.

Role of COX2 as a Biomarker for Estimating Survival of Patients With Clinical Stage I Gastric Cancer

The prognostic significance of biomarkers related to gastric cancer prognosis has not been fully elucidated. The aim of study was to use immunohistochemical biomarkers to reveal prognosis. A total of 682 patients who had undergone curative surgery were evaluated regarding the correlation of prognosis and immunohistochemical biomarkers. The COX2-positive groups showed a poor 5-year overall and disease-free survival. Further analysis revealed that COX2 positivity was a significant risk factor for poorer disease-free survival in the group with clinical stage I disease (p=0.016). We also noted a marked trend between COX2 positivity and poorer overall survival. The COX2-positive group showed general postoperative pathological up-staging compared with the COX2-negative group. This study showed the potential of COX2 as a biomarker for gastric cancer prognosis. Preoperative evaluation of COX2 might be a useful tool for generating optimal treatment strategies in patients with clinical stage I gastric cancer.

Cyclo-oxygenase-2 Expression Is Associated With Lymph Node Metastasis in Oropharyngeal Squamous Cell Carcinoma Under the New TNM Classification.

This study aimed to investigate p16 and COX2 expression in oropharyngeal squamous cell carcinoma (OPSCC), and evaluate the prognostic role of COX2 expression under the new TNM classification. Biopsy specimens obtained from 75 patients with OPSCC were stained for p16 and COX2 expression immunohistochemically. The results and clinical records were analyzed retrospectively. Fifty-nine patients (79%) were positive for p16. COX2 expression was correlated with poor relapse-free survival in patients overall, and in p16-positive patients. Smoking was positively associated with COX2 expression. Moreover, both positive COX2 expression and anterior wall tumor subsite were independently correlated with lymph node metastasis, which was the only independent prognostic factor in p16-positive OPSCC. The p16-positive rate in this study was comparable with that in the USA and Europe, and higher than that in other Asian countries. COX2 expression might affect the prognosis of p16-positive OPSCC through promoting lymph node metastasis.

Prognostic and therapeutic implications of lysyl oxidase and cyclooxygenase 2 expressions in epithelial ovarian carcinoma

Background: New prognostic and predictive biomarkers for better choice and improving the current therapies for ovarian cancer are greatly needed. This study aimed to investigate the prognostic and therapeutic importance of lysyl oxidase (LOX) and cyclooxygenase 2 (COX2) expressions in epithelial ovarian carcinoma. Methods: We performed immunohistochemical analysis on formalin-fixed paraffin sections of epithelial ovarian tumors. The association between their expressions in epithelial ovarian carcinoma (EOC) with the survival as well as response to chemotherapy was analyzed. Results: The frequency of the nuclear expression of LOX and cytoplasmic expression of COX2 was significantly higher in malignant tumors than in benign and borderline tumors. Also, there were statistically significant relationships between pathological grades and both LOX and COX2 positivity in EOC being at the higher end for poorly differentiated tumors. Both LOX and COX2 expressions were also correlated significantly with higher tumor stage. Overexpression of either LOX or COX2 in EOC was significantly associated with poor survival. Moreover, LOX and COX2 positive expressions in EOC were associated with poor response to chemotherapy. Conclusions: The increased expressions of LOX and COX2 in EOC are associated with several adverse clinicopathologic parameters, including reduced survival and chemotherapy resistance thus suggesting a role for such biomarkers in disease progression.

EFFECT OF SUN EXPOSURE DURATION ON CYCLOOXYGENASE-2 EXPRESSION IN THE CONJUNCTIVA.

SUMMARYPterygium is a multifactorial proliferative pathologic change of bulbar conjunctiva. The purpose of this study was to determine the effect of the duration of exposure to solar radiation (expressed in years) on the incidence of positive cyclooxygenase-2 (COX-2) finding in conjunctival tissue in two groups of patients. Group 1 consisted of 68 patients with primary pterygium having undergone conjunctival autograft transplantation. Group 2 consisted of 43 patients with morphologically unchanged conjunctivae that were harvested during cataract surgery. All 111 specimens were submitted to immunohistochemical staining for monoclonal COX-2 antibody (1:100; M361701 MO A-HU, Dako, Santa Clara, California, USA). The immunostaining intensity in the surface epithelium was scored using the following grading system: 0 no immunostaining; + weak immunostaining (few cells being positive focally or scattered); ++ medium immunostaining; and +++ strong immunostaining (diffuse staining throughout the tissue). The analysis of COX-2 activity yielded 29 (42.6%) positive findings in group 1 and 27 (62.8%) positive findings in group 2. Group 2 consisted of statistically significantly older individuals with a history of considerably longer sun exposure. Statistical analysis proved the duration of exposure to solar radiation to be the most important factor in positive COX-2 findings.

Expression of cyclooxygenase 2 in oral submucous fibrosis: An immunohistochemical pilot study.

Introduction:Oral submucous fibrosis (OSF) is associated with inflammatory changes in at least some stages of the disease. Prostaglandin is one of the main inflammatory mediators and its production is controlled by various enzymes such as cyclooxygenase (COX). The genetic and pharmacological data strongly indicate that COX-2 should be investigated as a potential target for the prevention and treatment of OSF.Methodology:The study group comprised histologically confirmed specimens (n = 10 each) of early OSF, moderate OSF, advanced OSF and normal oral mucosa for comparison. Immunohistochemistry was performed with avidin–biotin technique and evaluated with scoring methods.Results:The difference in percentage of expression in normal tissue and OSF was statistically highly significant (P < 0.001). Positive COX-2 exhibited cytoplasmic staining. One-way analysis of variances test was performed to evaluate COX-2 expression in different grades of OSF. Cytoplasmic staining assessed in terms of intensity, percentage of expression and Q Score did not show any statistical difference (percentage of expression F = 0.029, P = 0.971; Q Score F = 0.154, P = 0.858).Conclusions:Our study indicates that COX-2 may be an important marker of disease progression and might be a reliable prognostic indicator.