Abdominal aortic aneurysm (AAA) is a late-age onset disorder that affects a high percentage of the population in industrialized countries, and rupture of AAA is associated with high mortality rates ( 1 ). The etiology of AAA is complex with a relevant contribution of genetic factors ( 2 ). Although much effort has been made to clarify the mechanism of AAA development, currently the only effective approach to prevent aneurysm rupture is surgical repair by conventional or endovascular techniques.Evidence has been established for a relationship between atherosclerosis and AAA, both disorders being characterized by an underlying chronic infl ammation . However, there are marked differences between atherosclerotic lesions and AAA. Whereas atherosclerotic plaque is characterized by leukocyte infi ltration at the lumen site and hyperproliferation of vascular smooth muscle cells (VSMCs) causing neointimal hyperplasia, AAA is characterized by leukocyte infi ltration into adventitia and depletion of VSMCs in the media. Other relevant features of AAA are the wall tension strength breakdown caused by proteolytic enzymes progressively destructing elastic fi bers ( 3 ) and hypervascularization of aortic tissue. It has been proposed that this vascularization might contribute to the development and rupture of aneurysms ( 4, 5 ). Abstract We investigated the prostaglandin (PG)E

The presence of IL-1 in human cancers is associated with aggressive tumor biology but its prognostic value is unknown. We studied whether IL-1α expression is a prognostic marker of distant metastasis in patients with head and neck squamous cell carcinoma (HNSCC). IL-1α mRNA and protein levels were determined in tumor samples and cancer cell lines using RT-PCR and ELISA. The effects of constitutive IL-1α expression by tumor lines were characterized. IL-1α mRNA and protein secretion were higher in tumor samples from patients who later developed distant metastasis than in patients who did not. By using distant metastasis as a dependent variable, patients were classified into two categories of IL-1α transcript-levels. The high-IL-1α group had a significantly lower five-year distant metastasis-free survival than the low-IL-1α group [70.0% (CI 95%: 55.9-84.1%) vs 94.7% (CI 95%:90.2-99.2%)]. When IL-1α transcript-levels were combined with clinical factors related to tumor metastasis, the predictive power of the model increased significantly. Additionally, transcript levels of IL-1α correlated significantly with those of the IL-1 family genes and genes related to the metastatic process. IL-1 treatment of microvascular endothelial cells increased adhesion of HNSCC cells but no differences were found based on constitutive IL-1α expression by tumor cells. Nevertheless, IL-1α produced by tumor cells effectively increased their transmigration across the endothelium. We found a significant relationship between IL-1α expression and development of distant metastasis in HNSCC patients. IL-1α expression could help to define a subset of patients at high risk of distant metastasis who could benefit from adjuvant treatment.

Eicosanoids derived from polyunsaturated fatty acids are soluble mediators that exert a key role in the physiopathology of many disorders, including infl ammation, thrombosis, and cancer. Prostanoids derived from arachidonic acid (AAc) through the cyclooxygenase (COX) pathway are particularly relevant. The increasing interest in the role of prostanoids in the context of cancer originates in the large epidemiological trials that showed that COX-inhibiting nonsteroidal anti-infl ammatory drugs could be benefi cial against the development and growth of malignancies ( 1 ).Prostaglandin (PG)H 2 is the common cyclic-peroxide intermediate in the biosynthesis of prostanoids derived from AAc. The other prostanoids are formed in reactions catalyzed by specifi c synthases acting on PGH 2 ( 2 ). In contrast with the ubiquitous expression of COXs, expression of downstream synthases confers a cell-specifi c prostanoid profi le. COX-2 receives the most attention because, unlike COX-1, which is widely expressed, its expression is restricted in nonpathologic settings to a few cell types and tissues, but it is over-expressed in a wide range of cell types in tumors and infl amed tissues. COX-2 is transiently and Abstract Prostaglandin (PG)E 2 is relevant in tumor biology, and interactions between tumor and stroma cells dramatically infl uence tumor progression. We tested the hypothesis that cross-talk between head and neck squamous cell carcinoma (HNSCC) cells and fi broblasts could substantially enhance PGE 2 biosynthesis. We observed an enhanced production of PGE 2 in cocultures of HNSCC cell lines and fi broblasts, which was consistent with an upregulation of COX-2 and microsomal PGE-synthase-1 ( mPGES-1) in fi broblasts. In cultured endothelial cells, medium from fi broblasts treated with tumor cell-conditioned medium induced in vitro angiogenesis, and in tumor cell induced migration and proliferation, these effects were sensitive to PGs inhibition. Proteomic analysis shows that tumor cells released IL-1, and tumor cell-induced COX-2 and mPGES-1 were suppressed by the IL-1-receptor antagonist. IL-1 ␣ levels were higher than those of IL-1 ␤ in the tumor cell-conditioning medium and in the secretion from samples obtained from 20 patients with HNSCC. Fractionation of tumor cellconditioning media indicated that tumor cells secreted mature and unprocessed forms of IL-1. Our results support the concept that tumor-associated fi broblasts are a relevant source of PGE 2 in the tumor mass. Because mPGES-1 seems to be essential for a substantial biosynthesis of PGE 2 , these fi ndings also strengthen the concept that mPGES-1 may be \a target for therapeutic intervention in patients with HNSCC. Abbreviations: AAc, arachidonic acid; COX, cyclooxygenase; cPGES, cytosolic isoform of prostaglandin E synthase; FaDu-CM, FaDu-conditioned medium; HNSCC, head and neck squamous cell carcinoma; HUVEC, human umbilical vein endothelial cells; IL-1ra, interleukin-1 receptor antagonist; mPGES-1, microsomal prostaglandin E-synthase-1; MW, molecular weig...

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