COX–2 is overesxpressed in ovarian endometriosis and might represent a therapeutic target

Abstract Cyclooxygenase-2 (COX-2) is the key enzyme involved in prostaglandin synthesis. It appears to support the growth of a number of solid tumours including colon, breast, ovary, lung and uterine cervix and may be an important therapeutic target in at least some of these tumours. COX-2 expression has recently been evaluated (by immunohistochemistry using polyclonal anti-COX-2 antibodies) in multiple myeloma (MM) where expression was documented in 33–57% of patients. COX-2 expression in these studies was strongly associated with an adverse outcome. In addition there is some emerging data to suggest that the use of aspirin in MM may improve survival rates. In order to further evaluate this we have used a monoclonal antibody (Clone SP21, Labvision, Fremont, Ca) to assess COX-2 expression in both normal and neoplastic plasma cells. 52 specimens were assessed using standard streptavidin-biotin immunoperoxidase techniques using a known COX-2+ colon cancer as a positive control. Strong uniform COX-2 expression was seen in 32/33 (97%) of myeloma patients assessed and was also documented in all patients with MGUS (n=10). COX-2 expression was also documented in reactive plasmacytic lesions (oral mucosa, skin and lymph node, n=6) as well as normal bone marrow plasma cells (n=6). Megakaryocytes stained positively in all bone marrow biopsies examined and provided a useful positive internal control while erythroid, myeloid and lymphoid cells were consistently negative. We would conclude that COX-2 is strongly expressed by both normal and neoplastic plasma cells suggesting that COX-2 is a potential therapeutic target in MM. The apparent increase in the proportion of myeloma patients expressing COX-2 in the present study reflects the use of a monoclonal antibody in our immunohistology studies. The fact that polyclonal antibodies identify a lower proportion of patients who appear to have an inferior outcome suggests that the level of expression is of prognostic significance rather than its presence or absence. This is worthy of further study using more appropriate techniques such as RQ-PCR.

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COX-2 expression in thymomas and thymic carcinomas: a novel therapeutic target?

Diagnostic Pathology ◽

10.1186/1746-1596-2-s1-s3 ◽

2007 ◽

Vol 2 (Suppl 1) ◽

pp. S3 ◽

Cited By ~ 4

Author(s):

RJ Rieker ◽

PhA Schnabel ◽

G Mechtersheimer ◽

M Thomas ◽

H Dienemann ◽

...

Keyword(s):

Therapeutic Target ◽

Cox 2 ◽

Thymic Carcinomas ◽

Novel Therapeutic

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CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma

Veterinary Sciences ◽

10.3390/vetsci5030072 ◽

2018 ◽

Vol 5 (3) ◽

pp. 72

Author(s):

Walaa Nasry ◽

Haili Wang ◽

Kathleen Jones ◽

Wessel Dirksen ◽

Thomas Rosol ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Tumor Cells ◽

Squamous Cell ◽

Therapeutic Target ◽

Oral Epithelium ◽

Tumor Invasiveness ◽

Cd147 Expression ◽

Cox 2

Feline oral squamous cell carcinoma (OSCC) is a highly invasive form of cancer in cats. In human OSCC, cluster of differentiation 147 (CD147) contributes to inflammation and tumor invasiveness. CD147 is a potential therapeutic target, but the expression of CD147 in feline OSCC has not been examined. Immunohistochemistry was used to determine if cyclooxygenase 2 (COX-2) and CD147 expression in feline OSCC biopsies was coordinated. Tumor cells were more likely to express COX-2 (22/43 cases or 51%) compared to stroma (8/43 or 19%) and adjacent oral epithelium (9/31 cases or 29%) (p < 0.05). CD147 was also more likely to occur in tumor cells compared to stroma and adjacent mucosa, with 21/43 (49%) of cases having >50% tumor cells with mild or moderate CD147 expression, compared to 9/28 (32%) in adjacent epithelium and only 5/43 (12%) in adjacent stroma (p < 0.05). In feline OSCC cell lines (SCCF1, SCCF2, and SCCF3), CD147 gene expression was more consistently expressed compared to COX-2, which was 60-fold higher in SCCF2 cells compared to SCCF1 cells (p < 0.05). CD147 expression did not correlate with COX-2 expression and prostaglandin E2 (PGE2) secretion, indicating that they may be independently regulated. CD147 potentially represents a novel therapeutic target for the treatment of feline OSCC and further study of CD147 is warranted.

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STAT3 Differentially Regulates TLR4-Mediated Inflammatory Responses in Early or Late Phases

International Journal of Molecular Sciences ◽

10.3390/ijms21207675 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7675

Author(s):

Akash Ahuja ◽

Eunji Kim ◽

Gi-Ho Sung ◽

Jae Youl Cho

Keyword(s):

Therapeutic Target ◽

Nuclear Translocation ◽

Inflammatory Responses ◽

Late Phase ◽

Early Time ◽

Prolonged Treatment ◽

No Production ◽

Time Points ◽

Raw264.7 Macrophages ◽

Cox 2

Toll-like receptor 4 (TLR4) signaling is an important therapeutic target to manage lipopolysaccharide (LPS)-induced inflammation. The transcription factor signal transducer and activator of transcription 3 (STAT3) has been identified as an important regulator of various immune-related diseases and has generated interest as a therapeutic target. Here, we investigated the time-dependent roles of STAT3 in LPS-stimulated RAW264.7 macrophages. STAT3 inhibition induced expression of the pro-inflammatory genes iNOS and COX-2 at early time points. STAT3 depletion resulted in regulation of nuclear translocation of nuclear factor (NF)-κB subunits p50 and p65 and IκBα/Akt/PI3K signaling. Moreover, we found that one Src family kinase, Lyn kinase, was phosphorylated in STAT3 knockout macrophages. In addition to using pharmacological inhibition of NF-κB, we found out that STAT3KO activation of NF-κB subunit p50 and p65 and expression of iNOS was significantly inhibited; furthermore, Akt tyrosine kinase inhibitors also inhibited iNOS and COX-2 gene expression during early time points of LPS stimulation, demonstrating an NF-κB- Akt-dependent mechanism. On the other hand, iNOS expression was downregulated after prolonged treatment with LPS. Activation of NF-κB signaling was also suppressed, and consequently, nitric oxide (NO) production and cell invasion were repressed. Overall, our data indicate that STAT3 differentially regulates early- and late-phase TLR4-mediated inflammatory responses.

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