Tumors have developed several forms of resistance to receptor-induced cell death. Here, we show that malignant mesothelial (MM) cell lines as well as primary MM cells and normal mesothelial (NM) cells express Fas and TNFrelated apoptosis-inducing ligand (TRAIL) receptors DR4 and DR5. We found that, although Fas expression levels are comparable, only MM cells are resistant to cell death. Furthermore, MM cells show resistance to TRAILinduced apoptosis. Caspase-8 (FLICE) is not activated by death receptors triggering in malignant cells whereas it is well activated by nonreceptor stimuli, such as UV radiation. We found that FLIP (FLICE-Inhibitory Protein) is constitutively expressed in all MM cell lines and is more expressed in primary MM cells than in NM cells. Knockdown of FLIP expression in MM cell lines, by a FLIPsiRNA, re-established the normal response to apoptosis induced by Fas or DR4/DR5, which was blocked by pretreatment with the caspase-8 inhibitor z-IETD-fmk. These results indicate that MM cells develop an intrinsic resistance to apoptosis induced by death receptors upregulating the expression of the antiapoptotic protein c-FLIP.

Our preliminary experience shows that the results of the laparoscopic approach are comparable to those of the open approach. However, the important advantages of laparoscopy over the open approach are its minimal invasiveness and precision of intervention. Moreover, laparoscopy allows treatment of other intra-abdominal pathological conditions using the same anesthesia, as in 10 patients in our series. We believe that ligating the testicular veins and artery is preferable to ligating the testicular veins only, even if the incidence of hydrocele is not negligible after the Palomo procedure.

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