Results: Actin-beta-106/193/384 fragment levels were significantly increased in patients with cancer compared to those in healthy individuals (each p < 0.001). DNA integrity was significantly decreased in patients with cancer (p < 0.001). Cell-free
DNA fragment levels were not different when comparing patients with nonseminoma and seminoma (p > 0.24). ROC analysis demonstrated that cell-free DNA levels distinguished patients with cancer from healthy individuals with 87% sensitivity and 97% specificity. Even in 31 patients in whom the established serum tumor markers a-fetoprotein, human chorionic gonadotropin, placental alkaline phosphatase and lactate dehydrogenase PS-341 ic50 were normal cell-free DNA levels allowed us to distinguish between patients with cancer and healthy individuals with 84% sensitivity and 97% specificity. Cell-free DNA levels were more frequently increased in patients with clinical stage 3 than in patients with stage 1 or 2 disease (p < 0.046).
Conclusions: Cell-free DNA levels are increased in patients with testicular cancer and they allow the accurate discrimination of healthy individuals.
The high sensitivity of cell-free DNA could facilitate the management of testicular cancer, especially in patients with conventional tumor markers that are not increased.”
“It is presently unclear whether the antiseizure effects exerted by NSAIDs are totally dependent on COX inhibition or not. To clarify this point we investigated whether 7-methyl-2-phenylimidazoi(1,2-b)pyridazine-3-carboxylic check details acid (DM1) and 6-methoxy-2-phenylimidazo(1,2-b)pyridazine-3-carboxylic acid (DM2), two imidazo(1,2-b)pyridazines structurally related to indomethacin (IDM) but ineffective in blocking COXs, retain IDM antiabsence activity. When administered by intraperitoneal injection in WAG/Rij rats, a rat strain which spontaneously develops
SWDs, both DM1 and DM2 dose-dependently suppressed the occurrence of these seizures. Importantly, these compounds were both more potent in suppressing SWD occurrence than IDM. As T-type channel blockade is considered a mechanism of action common to many antiabsence Cyclooxygenase (COX) drugs we explored by whole cell patch clamp electrophysiology in stably transfected HEK-293 the effect of DM1 and DM2 on Cav3.1 channels, the T-type channel subtype preferentially expressed in ventrobasal thalamic nuclei. Both these compounds dose-dependently suppressed the currents elicited by membrane depolarization in these cells. A similar T-type blocking effect was also observed when the cells were exposed to IDM. In conclusion, DM1 and DM2 whilst inactive on COXs, are potent antiabsence drugs. This suggests that compounds with structural features typical of NSAIDs may exert antiepileptic activity independently from COX inhibition and possibly by a direct interaction with T-type voltage-dependent Ca(2+) channels. (C) 2008 Elsevier Ltd. All rights reserved.