BACKGROUND.To propose ‘never‐smoking nonsmall cell lung cancer (NSCLC)’ as a separate entity, the clinicopathologic differences of operable NSCLC between never‐smoking patients and patients with a history of smoking were investigated.METHODS.The medical records of 1405 patients with primary NSCLC who underwent a complete resection at the study institution from 1974 through 2004 were reviewed for clinicopathologic variables and postoperative survival.RESULTS.The proportion of never‐smoking patients with NSCLC has been significantly increasing over 30 years, from 15.9% in the 1970s to 32.8% in the 2000s. A significantly greater proportion of female patients or adenocarcinoma patients was found in the ‘never‐smoking NSCLC’ group in comparison to the ‘smoking NSCLC’ group (85.8% vs 11.2% and 87.8% vs 49.1%, respectively). The proportion of pathologic stage IA disease for the ‘never‐smoking NSCLC’ group was significantly higher than that for the ‘smoking NSCLC’ group (40.1% vs 25.4%; P < .0001). With regard to both overall and cancer‐specific survival, the ‘never‐smoking NSCLC’ patient group was significantly superior to the ‘smoking NSCLC’ group. In addition to smoking status, the factors found to be significantly associated with the postoperative survival rate were sex, histologic type, T classification, and N classification by univariate analyses. A multivariate analysis revealed never‐smoking status to be an independent prognostic factor in addition to pathologic T and N classification.CONCLUSIONS.The differences in the clinicopathologic factors and survivals between the ‘never‐smoking NSCLC’ patient group and the ‘smoking NSCLC’ group suggest that NSCLC in never‐smokers should be considered a separate disease entity. Cancer 2008. © 2008 American Cancer Society.

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The maximum tolerated dose of AZD7762 in combination with gemcitabine, 1,000 mg/m(2) was determined as 21 mg in Japanese patients.

The rat auditory cortex is organized as a tonotopic map of sound frequency. This map is broadly tuned at birth and is refined during the first 3 weeks postnatal. The structural correlates underlying tonotopic map maturation and reorganization during development are poorly understood. We employed fluorescent dye ballistic labeling (“DiOlistics”) alone, or in conjunction with immunohistochemistry, to quantify synaptogenesis in the auditory cortex of normal hearing rats. We show that the developmental appearance of dendritic protrusions, which include both immature filopodia and mature spines, on layers 2/3, 4, and 5 pyramidal and layer 4 spiny nonpyramidal neurons occurs in three phases: slow addition of dendritic protrusions from postnatal day 4 (P4) to P9, rapid addition of dendritic protrusions from P9 to P19, and a final phase where mature protrusion density is achieved (>P21). Next, we combined DiOlistics with immunohistochemical labeling of bassoon, a presynaptic scaffolding protein, as a novel method to categorize dendritic protrusions as either filopodia or mature spines in cortex fixed in vivo. Using this method we observed an increase in the spine‐to‐filopodium ratio from P9–P16, indicating a period of rapid spine maturation. Previous studies report mature spines as being shorter in length compared to filopodia. We similarly observed a reduction in protrusion length between P9 and P16, corroborating our immunohistochemical spine maturation data. These studies show that dendritic protrusion formation and spine maturation occur rapidly at a time previously shown to correspond to auditory cortical tonotopic map refinement (P11–P14), providing a structural correlate of physiological maturation. J. Comp. Neurol. 519:3327–3345, 2011. © 2011 Wiley‐Liss, Inc.