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Notably in psychological impotence, there is a strong response to placebo treatment. Erectile dysfunction, tied closely as it is to cultural notions of potency, success and masculinity, can have severe psychological consequences. There is a strong culture of silence and inability to discuss the matter. In reality, it has been estimated that around 1 in 10 men will experience recurring impotence problems at some point in their lives. If unsuccessful, does not interfere with other treatments When administered in vitro, PDE5 inhibition induces apoptosis in colon carcinoma (15) and chronic lymphocytic leukemia cells (16). To determine whether similar effects could be observed in vivo, we used various transplantable mouse tumors, including CT26WT (a colon carcinoma; Fig. 1 A), the more aggressive variant C26GM (Fig. 1 B), TS/A (a mammary adenocarcinoma; Fig. 1 C), and the MCA203 fibrosarcoma (Fig. 1 D). PDE5 inhibitors were administered starting on the day of tumor challenge. Sildenafil and tadalafil significantly delayed tumor outgrowth by 50 to 70% in immune-competent mice, although all mice ultimately died (Fig. S1, available at http://www.jem.org/cgi/content/full/jem.20061104/DC1). Similar results were obtained even if sildenafil treatment was started on day 7 after tumor challenge in the CT26WT model (Fig. S2). The fact that no difference in tumor outgrowth was seen between early versus late administration of sildenafil suggests that PDE5 inhibition does not appreciably affect the early phases of tumor uptake but rather influences the later stages of tumor outgrowth. Because the addition of sildenafil to cultured CT26WT cells did not increase their apoptosis or affect their doubling time (unpublished data), we conclude that sildenafil does not have a direct antitumor effect but rather interferes in host–tumor interactions. 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