肺癌CT普查--疾病分期与肿瘤大小的关系

目的：肺癌分期与肿瘤直径的关系已被证实是一个预后指标,因此被纳入1986年肺癌分类的国际系统。近年来由于CT飞速发展,人们可以诊断出更小的肺癌,于是有人提倡对肺癌Ⅰ期进一步分期,即根据肿瘤直径小于还是大于30mm,将无确切远处淋巴结转移的病例（Ⅰ期病例）细分为Ⅰa和Ⅰb期。在诊断无症状（即潜伏）的肺癌时,CT普查的开展使人们考虑肿瘤大小的预后价值。在此我们对CT普查诊断的无症状潜伏型肺癌作了分期与大小关系的报道。     

Mechanisms which mediate the antiapoptotic effects of angiopoietin-1 on endothelial cells

The main objective of this study was to identify molecular mechanisms through which angiopoietin-1 (Ang-1), a ligand for Tie-2 receptors, influences endothelial cell apoptosis. Human umbilical vein endothelial cells were cultured in a medium enriched with 2% fetal bovine serum (FBS) and growth supplements. Apoptosis was induced over 24 h by reducing FBS to 0.1%. Activation of caspase-9, -8, -7, and -3 and the expression of Bcl-2 family proteins, inhibitors of apoptosis (IAPs), cytochrome c, as well as Smac proteins were evaluated with immunoblotting. Ang-1 clearly attenuated serum deprivation-evoked apoptosis, an effect which required Tie-2 receptor activation. Activation of caspase-9, -7, and -3, but not caspase-8, was inhibited by Ang-1. The inhibitory effects of Ang-1 on apoptosis and caspase activation were reversed by a PI-3 kinase inhibitor (wortmannin). Ang-1 exposure upregulated the expression of Survivin but not XIAP (members of IAPs), reduced the cystosolic levels of Smac, but not that of cytochrome c, and had no effect on the expression of Bcl-2 family proteins. This is the first study to report on the mitochondrial mechanisms through which Ang-1 inhibits apoptosis and to investigate the role of the newly discovered Smac. We conclude that Ang-1 inhibits endothelial cell apoptosis through several pathways, which include PI-3 kinase/AKT activation, inhibition of Smac release from the mitochondria, and upregulation of Survivin protein.     

Endocrine-disrupting activities in vivo of the fungicides tebuconazole and epoxiconazole.

The triazole fungicides tebuconazole and epoxiconazole were investigated for reproductive toxic effects after exposure during gestation and lactation. Rats were dosed with epoxiconazole (15 or 50 mg/kg bw/day) or tebuconazole (50 or 100 mg/kg bw/day) during pregnancy from gestational day (GD) 7 and continued during lactation until postnatal day (PND) 16. Some dams were randomly chosen for cesarean section at GD 21 to evaluate effects on sexual differentiation in the fetuses. Other dams delivered normally, and the pups were examined (e.g., anogenital distance [AGD] and hormone levels) at birth, at PND 13 or PND 16, and semen quality was assessed in adults. Both tebuconazole and epoxiconazole affected reproductive development in the offspring after exposure in utero. Both compounds virilized the female offspring as shown by an increased AGD PND 0. Furthermore, tebuconazole had a feminizing effect on male offspring as shown by increased nipple retention. This effect was likely caused by the reduced testosterone levels seen in male fetuses. Tebuconazole increased the testicular concentrations of progesterone and 17alpha-hydroxyprogesterone in male fetuses, indicating a direct impact on the steroid synthesis pathway in the Leydig cells. The high dose of epoxiconazole had marked fetotoxic effects, while the lower dose caused increased birth weights. The increased birth weights may be explained by a marked increase in testosterone levels in dams during gestation. Common features for azole fungicides are that they increase gestational length, virilize female pups, and affect steroid hormone levels in fetuses and/or dams. These effects strongly indicate that one major underlying mechanism for the endocrine-disrupting effects of azole fungicides is disturbance of key enzymes like CYP17 involved in the synthesis of steroid hormones.     

Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma

Background  

Despite extensive research, the five-year survival rate of oral squamous cell carcinoma (OSCC) patients has not improved. Effective treatment of OSCC requires the identification of molecular targets and signaling pathways to design appropriate therapeutic strategies. Several genes from the mTOR signaling pathway are known to be dysregulated in a wide spectrum of cancers. However, not much is known about the involvement of this pathway in tumorigenesis of OSCC. We therefore investigated the role of the tumor suppressor genes, TSC1 and TSC2, and other members of this pathway in tumorigenesis of OSCC.