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A family of 20 tris-azaaromatic quaternary ammonium (AQA) compounds were tested for their inhibition of alpha7 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus laevis oocytes. The potency of inhibitory activity was related to the hydrophobic character of the tris head groups. Two tris-AQA compounds were studied in detail: the highly effective inhibitor 1,3,5-tri-[5-(1-quinolinum)-pent-1-yn-1-yl]-benzene tribromide (tPyQB) and the less potent antagonist 1,3,5,-tri-{5-[1-(2-picolinium)]-pent-1-yn-1-yl}benzene tribromide (tPy2PiB). In addition, we evaluated 1,2,4,5-tetra-{5-[1-(3-benzyl)pyridinium]pent-1-yl}benzene tetrabromide (tkP3BzPB), a tetrakis-AQA with very hydrophobic headgroups. We compared the activity of the AQA compounds to the frequently used alpha7-antagonist methyllycaconitine (MLA). Both tPyQB and tkP3BzPB were selective antagonists of alpha7. However, although inhibition by tPyQB was reversible within 5 min, the recovery time constant for tkP3BzPB inhibition was 26.6 +/- 0.8 min, so that the equilibrium inhibition in the prolonged presence of nanomolar concentrations of tkP3BzPB was nearly 100%. The potency, selectivity, and slow reversibility of tkP3BzPB were comparable with or greater than that of MLA. The inhibitory actions of tPyQB, tPy2PiB, and tkP3BzPB were evaluated on the acetylcholine (ACh)-evoked responses of native nAChRs in rat brain slices. The alpha7-mediated responses of hippocampal interneurons were effectively reduced by 1 microM tPyQB and tkP3BzPB but not tPy2PiB. In rat medial septum, tkP3BzPB produced a greater inhibition of ACh-evoked responses of cells with fast inward currents (type I) than of cells with predominantly slow kinetics (type II), suggesting that tkP3BzPB can block alpha7 yet preserve the responsiveness of non-alpha7 receptors. These agents might be helpful in elucidating complex receptor responses in brain regions with mixed populations of nAChRs.

Background: Sleeve recestion for lung cancer can get similar tumor and lymph node resection rate as pneumonectomy, with less influence on pulmonary function and much improvement of quality of life. The aim of this study is to compare the 5-year survival and complications of sleeve resection and pneumonectomy for lung cancer., Methods: Survival analysis was used to investigate the 5-year survival of 173 patients undergoing sleeve resection and 435 patients undergoing pneumonectomy from January 1990 to December 2000. Their complication and perioperative motality were also analyzed., Results: The overall 5-year survival for sleeve resection and pneumonectomy was 42.3% and 30.9%, respectively (P=0.007). 5-year survival of right lung sleeve resection was better than that of left lung [P=0.004 (N0), 0.025 (N1), 0.042 (N2)]. In left lung cancer patients without nodal involvement, the survival after sleeve resection was better than that after pneumonectomy. There was no survival difference between N1 and N2 lung cancer patients. Survival was not significantly different for bronchoplasty and pulmonary arterioplasty and pneumonectomy. The incidence rate of pneumonia and arrhythmia for sleeve resection was less than those for pneumonectomy (P=0.0019), and no significant difference of mortality was observed between the two groups., Conclusions: In lung cancer patients suitable for sleeve resection or pneumonectomy, sleeve resection should be performed for right lung cancer and left lung cancer of stage I. Bronchoplasty and pulmonary arterioplasty don't prolong the survival of lung cancer patients compared with pneumonectomy.

Background: The roles of nuclear factor kappa B (NF-kappa B) and activating protein 1 (AP-1) become well-known in cell apoptosis and proliferation and oncogenesis. This study aims to explore expression of NF-kappa B and AP-1 in non-small cell lung cancer (NSCLC), the relationship between them and their function on expression of cyclin D1 and caspase 3 in NSCLC., Methods: Protein expression of NF-kappa B, AP-1 , cyclin D1 and caspase 3 was detected by Western blot and mRNA expression of cyclin D1 and caspase 3 by RT-PCR. Correlation between NF-kappa B and AP-1 was analyzed using bivariate correlate analysis., Results: Of all 45 NSCLC patients, the expression of NF-kappa B and AP-1 in NSCLC was higher than that in normal lung tissues (0.6047 versus 0.2798, P < 0.01). Protein and mRNA expression of cyclin D1 in lung cancer tissues with higher NF-kappa B and AP-1 protein expression was higher than in those with lower NF-kappa B and AP-1 protein expression (P < 0.01), while protein and mRNA expression of caspase 3 in lung cancer tissues with higher NF-kappa B and AP-1 protein expression was lower than in those with lower NF-kappa B and AP-1 protein expression (P < 0.01). There was significant correlation between NF-kappa B and AP-1 (r=0.800, P < 0.01)., Conclusions: Transcription factors, NF-kappa B and AP-1 may play important roles in oncogenesis and development of NSCLC.

Background: Biochemical and genetic researches suggest that ras protein plays an important role in transduction process of cell proliferation differentiation signals from activated transmembrane receptors to substream protein kinases. This study is to explore the expression of ras, p38, both of which are members of MAPK (mitogen activated protein kinases) signal transduction pathway, and STAT3 (signal transducer and activator of transcription 3) in non-small cell lung cancer, and the association among them., Methods: Forty-two resected lung cancer and paracancerous lung tissue samples were used to determine the protein expression of ras, p38 and STAT3 with Western blot, the mRNA expression of p38 and STAT3 in lung cancer tissues of various ras protein expression with RT-PCR. The location of p38 and STAT3 in lung cancer tissues was revealed with immunofluorescent staining., Results: The relative protein expressions of ras, p38 and STAT3 were 0.6012, 0.6724, 0.5119 in cancer tissues, and 0.2793, 0.3071, 0.1917 in paracancerous lung tissues, respectively (P < 0.01). The protein and mRNA expressions of p38 and STAT3 ( 0.7624 and 0.6262; 1.0309 and 1.0538) in cancer tissues with higher ras protein expression were remarkably higher than those with lower ras protein expression (0.4715 and 0.2569; 0. 6569 and 0.3437, P < 0.01). There was a significant correlation between the expression of ras, p38 and STAT3 (correlation coefficient: 0.809 and 0.842, P < 0.01), and so was the p38 and STAT3 (correlation coefficient: 0.829, P < 0.01)., Conclusions: Abnormal expressions of STAT3 and some factors of ras-MAPK signal transduction pathway exist in the oncogenesis and development of non-small cell lung cancer, and many of them may have crosstalk.

Background: To explore predictors of mediastinal and intrapulmonary pathologic lymph node involvement in clinical stage I non-small cell lung cancer., Methods: From July 1999 to April 2001, 159 patients with clinical stage I non-small cell lung cancer underwent lobectomy and complete mediastinal or intrapulmonary lymph node dissection. All the resected lymph nodes were pathologically analyzed to find out pathologic involvement. Univariate and multivariate analyses were used to clarify predictors of lymph node metastasis., Results: Of all 159 patients, 37 (23%) had pathologic lymph node metastasis. According to logistic regression analysis, tumor size, grade of cell differentiation, and pleural invasion were the significant predictors of lymphatic metastasis ( P=0.003, P=0.004, P =0.005). Patients with 2 or more factors were more liable to have lymph node metastasis than those with less than 2 factors ( P < 0.001)., Conclusions: When patients with clinical stage I non-small cell lung cancer have such clinical factors as tumor diameter > 2.0 cm, moderate or poor differentiation, or pleural invasion, they will be more liable to have lymph node metastasis. Therefore, it should be more prudent to select therapeutic way and judge their prognosis.