The extent of stained area in specimen thus appears to be more important than the intensity of staining in terms of evaluation of COX-2 performance as a diagnostic and prognostic marker of cutaneous melanoma.
In conclusion, by using this dual approach we propose that the COX-2 and H<sub>2</sub>S pathways could be regarded as novel therapeutic targets/tools to generate new treatment options based on "combination therapy" for melanoma.
The aim was to evaluate the prognostic significance of expression of CD163 and CD68 (TAMs' markers) and their correlation with vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) expression in cutaneous melanoma.
In addition, clinical data showed that high expression of TRIP4 was positively correlated with increased expression of COX-2 and iNOS and predicted poor prognosis in a cohort of 100 melanoma patients.
This study demonstrates the bioefficacy and gives mechanistic insights into a plant galactolipid 1,2-di-O-linolenoyl-3-O-β-galactopyranosyl-sn-glycerol (dLGG) against metastatic melanoma using a syngeneic mouse model implanted with B16<sup>COX-2/Luc</sup> melanoma. dLGG-20 (p.o. dLGG 20 mg/kg) and anti-cancer drug CP-2 (i.p. cisplatin 2 mg/kg) treatment significantly inhibited lung metastasis of melanoma in mice 91 and 57%, respectively, as determined by bioluminescence intensity.
Taken together, our findings demonstrate that COX-2 and p-Akt1 play an important combined role during melanoma progression and are associated with highly metastatic tumors and survival rates in patients with MM.
Plumbagin and Celecoxib are two agents that were identified to synergistically kill melanoma cells by inhibiting the COX-2 and STAT3 pathways, which are constitutively activated in up to 70% of melanomas.
This work describes the anti-inflammatory effect of the curcumin-analog compound, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate (DM1), and shows that DM1 modulates iNOS and COX-2 gene expression in cultured RAW 264.7 cells and induces autophagy on human melanoma cell line A375.
Our findings suggest that COX-2 expression may become an useful diagnostic tool in defining melanoma malignancy as well as argue for a possible therapeutic use of NSAID as add on therapy in selected cases.
Furthermore, iNOS expression correlated with the Breslow thickness, Clark level, and histological subtype in melanoma, while in nasopharyngeal carcinoma, significant association was seen with age at diagnosis, TNM, metastasis, response to treatment, and expression of COX-2.
Our results point to a role for COX-2 in angiogenesis and in the establishment of an inflammatory microenvironment, favourable to melanoma tumour progression.
Thus, this study details the development of selenocoxib-1-GSH, which is a nontoxic agent that targets the COX-2 and PI3K/Akt signaling pathways in melanomas to inhibit tumor development.
The data demonstrate that the HuR-mediated stabilization of COX-2 may represent a target of DHA action in melanoma cells and suggest the application of DHA in the prevention and therapy of melanoma.
Treatment of melanoma-patient-derived TAFs with IL-1α/β significantly enhanced their ability to suppress the proliferation and function of melanoma-specific cytotoxic T cells, and this inhibition was partially attributable to upregulation by IL-1 of COX-2 and the PD-1 ligands PD-L1 and PD-L2 in TAFs.
To investigate the effects of COX-2 inhibition on the tumor endothelium in vitro, we isolated tumor endothelial cells (TECs) from human melanoma and oral carcinoma xenografts in mice, in which we confirmed that tumor growth was suppressed by inhibiting angiogenesis with the COX-2is NS398.
Using a human 'model', in which the isolated limb is perfused with high doses of the chemotherapeutic melphalan (ILP), we identified a five-gene set (ATF3, CYR61, IER5, IL6, and PTGS2) of stress-induced genes that was consistently upregulated after ILP in all in-transit metastatic melanoma samples as well as in three melphalan-treated melanoma cell lines.
In immortalized rat brain GP8.3 EC cultures, conditioned media (CM) prepared from SK-MEL28 and OCM-1 melanoma cells significantly enhanced arachidonic acid release, cytosolic phospholipase A(2) (cPLA(2)) and Ca(+)-independent phospholipase A(2) (iPLA(2)) specific activities, and cell growth by 24 h. Inhibitors such as wortmannin and LY294002 (vs. PI3 kinase activity), AACOCF(3), (vs. cPLA(2) and iPLA(2)), PD98059 (vs. ERK1/2 activity) and NS-398 (vs. cyclooxygenase-2 activity, COX-2) were all able to block cell proliferation and motility determined using a scratch wound healing assay in melanoma CMs-stimulated EC monolayers.