No abstract

The antiapoptotic molecule galectin-3 was previously shown to regulate CD95, a member of the tumor necrosis factor (TNF) family of proteins in the apoptotic signaling pathway. Here, we question the generality of the phenomenon by studying a different member of this family of proteins [e.g., TNF-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in a wide variety of cancer cells]. Overexpression of galectin-3 in J82 human bladder carcinoma cells rendered them resistant to TRAIL-induced apoptosis, whereas phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY-294002) blocked the galectin-3 protecting effect. Because Akt is a major downstream PI3K target reported to play a role in TRAIL-induced apoptosis, we questioned the possible relationship between galectin-3 and Akt. Parental J82 and the control vector-transfected J82 cells (barely detectable galectin-3) exhibit low level of constitutively active Akt, resulting in sensitivity to TRAIL. On the other hand, J82 cells overexpressing galectin-3 cells expressed a high level of constitutively active Akt and were resistant to TRAIL. Moreover, the blockage of TRAIL-induced apoptosis in J82 cells seemed to be mediated by Akt through the inhibition of BID cleavage. These results suggest that galectin-3 involves Akt as a modulator molecule in protecting bladder carcinoma cells from TRAILinduced apoptosis. (Cancer Res 2005; 65(17): 7546-53)

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Benzodiazepines, antidepressants, antipsychotic agents, anti-arrhythmic agents, opioid analgesics and antihypertensive agents including a-receptor antagonists and b-receptor antagonists, but not angiotensin II receptor antagonists, have been implicated as risk factors for falls among community dwelling elderly people, and those in aged care hospitals and nursing homes. WHAT THIS STUDY ADDS• Using a case-crossover design, the study's findings provide the first evidence suggesting that newly initiating treatment using an angiotensin II receptor antagonist, candesartan, or etizolam, biperiden and zopiclone may be potential risk factors for falls in acute hospitals. AIMSThe present study aimed to evaluate the associations between medication use and falls and to identify high risk medications that acted as a trigger for the onset of falls in an acute care hospital setting. METHODSWe applied a case-crossover design wherein cases served as their own controls and comparisons were made within each participant. The 3-day period (days 0 to -2) and the 3-day periods (days -6 to -8, days -9 to -11 and days -12 to -14) before the fall event were defined as the case period and the control periods, respectively. Exposures to medications were compared between the case and control periods. Odds ratios (OR) and 95% confidence intervals (CI) for the onset of falls with respect to medication use were computed using conditional logistic regression analyses.