支气管动脉灌注化疗与栓塞治疗中晚期肺癌的疗效观察

目的：对比分析支气管动脉灌注化疗与支气管动脉灌注化疗十栓塞术治疗中晚期肺癌的临床疗效。方法：将我院2011年1月-2013年1月期间收治的76例中晚期肺癌患者随机分为两组,即观察组38例,对照组38例。观察组患者行支气管动脉灌注化疗联合栓塞术治疗,对照组患者行单纯支气管动脉灌注化疗治疗。分别对两组患者治疗后的临床治疗效果进行评价,同时观察两组患者治疗后的不良反应及并发症的发生情况。结果：观察组患者临床治疗的总有效率为84．21％,对照组为64．78％．两组比较,差异具有统计学意义（P〈0．05）。两组患者治疗后,观察组患者总不良反应率为23．67％,对照组为21．04％,两组比较．差异无统计学意义（P〉0．05）。且经对症处理后,均得到有效改善。结论：支气管动脉灌注化疗联合栓塞术治疗中晚期肺癌的,临床疗效明显优于单纯支气管动脉灌注化疗,且无明显不良反应及并发症的发生,安全性好,值得临床推广与应用。     

Mechanisms of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a chronic lung disease affecting premature infants with long term effect on lung function into adulthood. Multiple factors are involved in the development of BPD. This review will summarize the different mechanisms leading to this disease and highlight recent bench and clinical research targeted at understanding the role of the mesenchyme (both its cellular and extracellular components) in the pathogenesis of BPD.     

Dual character of Toll-like receptor signaling: Pro-tumorigenic effects and anti-tumor functions

As a major class of pattern-recognition receptors, Toll-like receptors (TLRs) play a critical role in defense against invading pathogens. Increasing evidence demonstrates that, in addition to infection, TLRs are involved in other important pathological processes, such as tumorigenesis. Activation of TLRs results in opposing outcomes, pro-tumorigenic effects and anti-tumor functions. TLR signaling can inhibit apoptosis and promote chronic inflammation-induced tumorigenesis. TLR activation in tumor cells and immune cells can induce production of cytokines, increase tumor cell proliferation and apoptosis resistance, promote invasion and metastasis, and inhibit immune cell activity resulting in tumor immune escape. In contrast, the engagement of other TLRs directly induces growth inhibition and apoptosis of tumor cells and triggers activation of immune cells enhancing anti-tumor immune responses. Thus, the interpretation of the precise function of each TLR in tumors is very important for targeting TLRs and using TLR agonists in tumor therapy. We review the role of TLR signaling in tumors and discuss the factors that affect outcomes of TLR activation.     

Chronobiologic Evaluation of Angiotensin-Converting Enzyme Activity in Serum and Lung Tissue from Normotensive and Spontaneously Hypertensive Rats

Angiotensin-converting enzyme (ACE) activity in serum and lung tissue from both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) was determined at six different circadian times. In WKY rats serum ACE varied significantly within 24 h, mainly due to reduced enzyme activity at 12:00 h. In SHR the 24-h profile of serum ACE did not exhibit time-dependent differences. Mean serum ACE activity over 24 h was significantly higher in WKY than in SHR. In lung tissue ACE activity did not depend on the circadian time in either strain. Mean enzyme activity in lung tissue was not different between WKY and SHR. We conclude that circadian changes in the activity of serum and tissue ACE are unlikely to play an important role in the regulation of the circadian blood pressure profile in both normotensive and spontaneously hypertensive rats.     

Light at Night Co‐distributes with Incident Breast but not Lung Cancer in the Female Population of Israel

Recent studies of shift‐working women have reported that excessive exposure to light at night (LAN) may be a risk factor for breast cancer. However, no studies have yet attempted to examine the co‐distribution of LAN and breast cancer incidence on a population level with the goal to assess the coherence of these earlier findings with population trends. Coherence is one of Hill's “criteria” (actually, viewpoints) for an inference of causality. Nighttime satellite images were used to estimate LAN levels in 147 communities in Israel. Multiple regression analysis was performed to investigate the association between LAN and breast cancer incidence rates and, as a test of the specificity of our method, lung cancer incidence rates in women across localities under the prediction of a link with breast cancer but not lung cancer. After adjusting for several variables available on a population level, such as ethnic makeup, birth rate, population density, and local income level, a strong positive association between LAN intensity and breast cancer rate was revealed (p<0.05), and this association strengthened (p<0.01) when only statistically significant factors were filtered out by stepwise regression analysis. Concurrently, no association was found between LAN intensity and lung cancer rate. These results provide coherence of the previously reported case‐control and cohort studies with the co‐distribution of LAN and breast cancer on a population basis. The analysis yielded an estimated 73% higher breast cancer incidence in the highest LAN exposed communities compared to the lowest LAN exposed communities.     

Rhamnetin and Cirsiliol Induce Radiosensitization and Inhibition of Epithelial-Mesenchymal Transition (EMT) by miR-34a-mediated Suppression of Notch-1 Expression in Non-small Cell Lung Cancer Cell Lines

Radioresistance is a major cause of decreasing the efficiency of radiotherapy for non-small cell lung cancer (NSCLC). To understand the radioresistance mechanisms in NSCLC, we focused on the radiation-induced Notch-1 signaling pathway involved in critical cell fate decisions by modulating cell proliferation. In this study, we investigated the use of Notch-1-regulating flavonoid compounds as novel therapeutic drugs to regulate radiosensitivity in NSCLC cells, NCI-H1299 and NCI-H460, with different levels of radioresistance. Rhamnetin and cirsiliol were selected as candidate Notch-1-regulating radiosensitizers based on the results of assay screening for activity and pharmacological properties. Treatment with rhamnetin or cirsiliol reduced the proliferation of NSCLC cells through the suppression of radiation-induced Notch-1 expression. Indeed, rhamnetin and cirsiliol increased the expression of tumor-suppressive microRNA, miR-34a, in a p53-dependent manner, leading to inhibition of Notch-1 expression. Consequently, reduced Notch-1 expression promoted apoptosis through significant down-regulation of the nuclear factor-κB pathway, resulting in a radiosensitizing effect on NSCLC cells. Irradiation-induced epithelial-mesenchymal transition was also notably attenuated in the presence of rhamnetin and cirsiliol. Moreover, an in vivo xenograft mouse model confirmed the radiosensitizing and epithelial-mesenchymal transition inhibition effects of rhamnetin and cirsiliol we observed in vitro. In these mice, tumor volume was significantly reduced by combinational treatment with irradiation and rhamnetin or cirsiliol compared with irradiation alone. Taken together, our findings provided evidence that rhamnetin and cirsiliol can act as promising radiosensitizers that enhance the radiotherapeutic efficacy by inhibiting radiation-induced Notch-1 signaling associated with radioresistance possibly via miR-34a-mediated pathways.     

Galactose 6-O-Sulfotransferases Are Not Required for the Generation of Siglec-F Ligands in Leukocytes or Lung Tissue

Eosinophil accumulation is a characteristic feature of the immune response to parasitic worms and allergens. The cell surface carbohydrate-binding receptor Siglec-F is highly expressed on eosinophils and negatively regulates their accumulation during inflammation. Although endogenous ligands for Siglec-F have yet to be biochemically defined, binding studies using glycan arrays have implicated galactose 6-O-sulfate (Gal6S) as a partial recognition determinant for this receptor. Only two sulfotransferases are known to generate Gal6S, namely keratan sulfate galactose 6-O-sulfotransferase (KSGal6ST) and chondroitin 6-O-sulfotransferase 1 (C6ST-1). Here we use mice deficient in both KSGal6ST and C6ST-1 to determine whether these sulfotransferases are required for the generation of endogenous Siglec-F ligands. First, we characterize ligand expression on leukocyte populations and find that ligands are predominantly expressed on cell types also expressing Siglec-F, namely eosinophils, neutrophils, and alveolar macrophages. We also detect Siglec-F ligand activity in bronchoalveolar lavage fluid fractions containing polymeric secreted mucins, including MUC5B. Consistent with these observations, ligands in the lung increase dramatically during infection with the parasitic nematode, Nippostrongylus brasiliensis, which is known to induce eosinophil accumulation and mucus production. Surprisingly, Gal6S is undetectable in sialylated glycans from eosinophils and BAL fluid analyzed by mass spectrometry. Furthermore, none of the ligands we describe are diminished in mice lacking KSGal6ST and C6ST-1, indicating that neither of the known galactose 6-O-sulfotransferases is required for ligand synthesis. These results establish that ligands for Siglec-F are present on several cell types that are relevant during allergic lung inflammation and argue against the widely held view that Gal6S is critical for glycan recognition by this receptor.     

Intérêt de la scintigraphie pulmonaire de perfusion dans les dilatations des bronches de l’enfant

IntroductionBronchiectasis is a chronic disease of the lungs by repeated respiratory infection. An early and adequate diagnosis and management reduce the morbidity and mortality of this disease. The aim of this study is to emphasize the importance of the combination of Computer Tomography (CT) and lung perfusion scan (SPP) in the diagnosis and therapeutic approach.Materials and methodsForty-three children were referred in the nuclear medicine department with a clinical diagnosis of bronchiectasis; they underwent a CT and a SPP.Results and conclusionBy analyzing the results of the SPP and CT separately, we conclude that there is no significant difference between the two investigations. The combination of the two explorations provides a gain in most surgical therapeutic orientation.     

肺癌中piR-932的表达及其生物学行为机制研究

目的研究肺癌干细胞中piR-932的表达,以期为肺癌的治疗提供参考。方法应用piRNA芯片检测肺癌于细胞中piRNAs的表达,应用基因芯片检测肺癌干细胞中基因表达的差异,并检测表达下调的基因之一——Latexin的甲基化程度。结果经诱导至EMT的肺癌干细胞中,piR-932的表达明显增高,而Latexin的表达显著下降,并且Latexin启动子区域CpG岛发生了明显的甲基化。结论piR-932可能通过促进Latexin的甲基化而正渊节肺癌干细胞的EMT过程,它可作为肺癌治疗的一个潜在靶点。