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ScienceDaily (Jan. 2, 2010) — A study in the Jan. 1 issue of the journal Sleep shows that erectile dysfunction was more common in older men with restless leg syndrome (RLS) than in those without RLS, and the magnitude of this association increased with a higher frequency of RLS symptoms.
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To exert a measurable antitumor effect, tumor-specific T cells must be present in sufficient numbers and capable of trafficking to their targets. A direct correlation exists between the number of tumor-infiltrating lymphocytes (TILs) and a favorable clinical outcome, as demonstrated in patients with metastatic ovarian cancer (20). Furthermore, the functional status of TILs has been correlated with a favorable prognosis in various human malignancies (20–24). Because PDE5 inhibition augments antitumor immunity, we asked whether sildenafil treatment altered both the number and activation state of TILs. Histological examination of CT26WT tumors revealed a greater intratumoral cellular infiltrate in the sildenafil-treated mice compared with the untreated controls (Fig. 4 A). To better evaluate these differences, C26GM-bearing mice received either tumor-primed or no T cells followed by sildenafil treatment or no additional therapy. The tumors were excised 9 d later, and single cell suspensions were obtained. The T cell infiltrate was analyzed by flow cytometry for CD4+ and CD8+ T cells. This approach enabled us to accurately examine the entire tumor mass and reliably quantify the infiltrating lymphocytic population. Although no increase in CD4+ T cells was observed with PDE5 inhibition (Fig. 4 B, inset), sildenafil treatment greatly increased CD8+ intratumoral infiltration with up-regulation of the activation markers CD69 and CD25 (Fig. 4 C). There were no differences in activation markers between the sildenafil-treated group and sildenafil + ACT, whereas a significant increase in intratumoral T cells were observed in the sildenafil + ACT–treated group compared with sildenafil alone (Fig. 4 B and Fig. S4, available at http://www.jem.org/cgi/content/full/jem.20061104/DC1).
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Sildenafil (Pfizer) was dissolved in the drinking water (20 mg/kg/24 h), given i.p. daily where indicated (20 mg/kg/24 h), or added to the cell cultures (50 mg/ml). 2 mg/kg/24 h tadalafil (Lilly ICOS) was administered i.p. In vivo treatments started on day 0 unless otherwise indicated.
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