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Werner's syndrome is a genetic disorder that causes premature aging due to loss-of-function mutations in a gene encoding a member of the RecQ helicase family. Both Werner's syndrome and cigarette smoking accelerate aging. No studies have examined the effect of cigarette smoke on Werner's syndrome protein.To investigate the role of Werner's syndrome protein in cigarette smoke-induced cellular senescence.Cellular senescence and amounts of Werner's syndrome protein were measured in fibroblasts isolated from patients with emphysema and compared with age-matched nonsmokers. The in vitro effects of cigarette smoke on amounts of Werner's syndrome protein, function, and senescence were also evaluated in primary human lung fibroblasts and epithelial cells.Cultured lung fibroblasts isolated from patients with emphysema exhibited a senescent phenotype accompanied by a decrease in Werner's syndrome protein. Cigarette smoke extract decreased Werner's syndrome protein in cultured fibroblasts and epithelial cells. Werner's syndrome protein-deficient fibroblasts were more susceptible to cigarette smoke-induced cellular senescence and cell migration impairment. In contrast, exogenous overexpression of Werner's syndrome protein attenuated the cigarette smoke effects.Cigarette smoke induces cellular senescence and cell migration impairment via Werner's syndrome protein down-regulation. Rescue of Werner's syndrome protein down-regulation may represent a potential therapeutic target for smoking-related diseases.

This study evaluates the role of scavenger receptor class A member 3 (SCARA3) in multiple myeloma (MM). SCARA3 expression was induced upon treatment with oxidative stressors (ionizing radiation and chemotherapeutic drugs). An epigenetic inactivation of SCARA3 was noted in MM.1S myeloma cells. Myeloma cell killing by dexamethasone and bortezomib was inhibited by up-regulation of SCARA3 while SCARA3 knockdown sensitized myeloma cells to the drugs. Clinical samples showed an inverse correlation between SCARA3 gene expression, myeloma progression, and favorable clinical prognosis. In MM, SCARA3 protects against oxidative stress-induced cell killing and can serve as predictor of MM progression and therapeutic response.

5059 Background: CALYPSO is a randomized trial that showed superiority of carboplatin-pegylated liposomal doxorubicin (C-PLD) over carboplatin-paclitaxel (C-P) in relapsed ovarian cancer (ROC). Bec...

5052 Background: CALYPSO is a large international randomized phase III trial comparing C-PLD and C-P in pts with OC in late relapse. Results of the progression-free survival (PFS), the primary endpoint, suggest a benefit in pts treated with C-PLD with a hazard ratio (HR) of 0.82 (P =.005). Overall severe non-hematologic toxicity (36.8% v 28.4%; P < .01) - including alopecia, neurotoxicity and carboplatin hypersensitivity leading to early discontinuation (15% v 6%; P < .001) - occurred more frequently in the C-P arm. Methods: From 04/05 to 10/07, 976 eligible pts were randomized to either C-P (carboplatin AUC 5 iv d1 + paclitaxel [P] 175 mg/m2 3h iv d1, q3w) or C-PLD (Carboplatin + PLD 30 mg/m2 iv d1 q4w) for at least 6 cycles. It was explored whether the treatment effect on PFS recently observed in CALYPSO was maintained after further treatment. OS of pts was analysed. Results: Median follow-up is 40 months (mo). 832 pts (86%) have progressed after CALYPSO treatment (C-PLD or C-P). At time of first progre...