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Background: As one of the leading cause of cancer-related deaths in the worldwide, lung cancer needs to be understood better. Nowadays, increasing point mutations of specific oncogenes are biomarkers used to predict the therapeutic effect of targeted therapy and lung cancer has entered the age of individual treatment. At present, many relevant researchers have suggested that EGFR is a biomarker used to predict the therapeutic effect of targeted therapy. A large number of evidence indicates that EGFR/Akt pathway plays important role in cancer growth and metastasis. Aim of the Study: In this paper, we found EGFR was a target of miR-646. Results: Overexpression of miR-646 not only downregulated EGFR/Akt pathway, but also inhibited lung cancer cell proliferation and metastasis. At the same time, miR-646 was a prognosis factor for overall survival. Conclusion: Our finding could provide new insights into the molecular therapeutic of lung cancer.

The bronchus is an imperfect elastic structure because part of the energy transmitted in inspiration is not recovered in expiration. This phenomenon is known as bronchial hysteresis. The aim of this paper is to demonstrate bronchial hysteresis using morphometric techniques: differences in the wall and the bronchial lumen, between inspiration and expiration. Sixty disease-free Fischer rats were used, organized into 4 groups. The lungs from the first and second groups were fixed in inflation at 10 and 20 cm of H(2)O transpulmonary pressure (Ptp), respectively. Those taken from the third and fourth groups were fixed in deflation at 20 and 10 cm Ptp, respectively. The lungs were removed from the thorax, filled with air, and fixed via the pulmonary artery. A morphometric study of the following variables was performed: pulmonary volume (P(v)), dead space (DS) internal bronchial area (A(i)), which is the area of the bronchial lumen, and total wall area (WA(t)), which is the area of the bronchial wall. The lungs fixed in deflation gave higher values for all the variables than those fixed in inflation. The P(v), DS, and A(i) increased/decreased with the rise/fall of the Ptp; A(i) was the only variable to display statistically significant values (P.05) when the Ptp was modified. WA(t) showed statistically significant differences between the lungs fixed in inflation and deflation and underwent no modification when the Ptp was varied. This study supports the hypothesis that bronchial hysteresis can be demonstrated using morphometric techniques because differences were observed in the lumen and wall of the bronchus between inflation and deflation.

This paper describes a series of studies on the lung tumorigenic activities of polycyclic aromatic hydrocarbons (PAHs) in strain A/J mice, their ability to form PAH-DNA adducts in lung tissues, and their ability to mutate the Ki-ras oncogene in PAH-induced tumors. Seven PAHs were studied: cyclopenta[cd]pyrene (CPP), benzo[a]pyrene (B[a]P), benzo[b]fluoranthene (B[b]F), dibenz[a,h] anthracene (DBA), 5-methylchrysene (5MC), benz[j]aceanthrylene (B[j]A), and dibenzo[a,l]pyrene (DB[a,l]P). The dose-response data for the PAHs revealed 100-fold differences in tumor potency based on dose, with the order of activity DB[a,l]P, DBAB[j]A5MCCPP B[a]PB[b]F. Large differences in tumor multiplicity were also observed between the PAHs. DNA adducts were measured by 32P-postlabeling techniques on DNA from lungs of mice treated with these PAH's. DB[a,l]P gave syn- and anti-fjord-region diol-epoxide adducts of dAdo and dGuo; DBA gave both bay-region diol-epoxide-dGuo and bisdihydrodiol-epoxide adducts; CPP gave cyclopenta-ring-dGuo adducts; B[j]A gave a mixture of cyclopenta-ring-dGuo and -dAdo adducts; 5MC gave anti-bay-region diol-epoxide-dGuo adducts; B[a]P gave bay-region diol-epoxide-dGuo adducts; and B[b]F gave 5-hydroxy-B[b]F-diol-epoxide-dGuo adducts. Ki-ras codon 12 and 61 mutation analysis of PAH induced tumors was performed using PCR and dideoxy sequencing methods. DB[a,l]P gave both codon 12 and codon 61 mutations. High proportions of codon 12 TGT mutations from B[a]P-, B[b]F- and 5MC-, induced tumors and CGT mutations from CPP- and B[j]A-induced tumors were observed. DBA produced no mutations in Ki-ras codons 12 or 61 by direct sequencing. The interrelationships between the tumorigenesis, DNA adduct, and oncogene mutation data are discussed.

A hitherto unexpected synergism between the oxidant air pollutants ozone or nitrogen dioxide and a respirable-sized aerosol of ammonium sulfate was previously observed during controlled exposures of rats to these substances. In this paper we examine biochemical and morphometric changes in lungs of rats exposed for 3, 7, or 14 days to ozone (0.64-0.96 ppm), with or without an accompanying aerosol (approximately 1 micrometer mass median aerodynamic diameter) of ammonium sulfate (5 mg/m3). After 3 days of exposure to the mixture of pollutants, rat lung macrophage and macrophage precursors (monocytes) were increased 2- to 3-fold, fibroblasts were increased 2-fold, and apparent collagen synthesis rates were increased 2.5-fold, fibroblasts were increased 2-fold, and apparent collagen synthesis rates were increased 2.5-fold, as compared with values from animals exposed to ozone alone. Continued exposure to ozone alone for 7 or 14 days seemed to mimic changes seen at 3 days with the mixture of pollutants. Total number of lesions per lung was the same for ozone exposure with and without accompanying aerosol; lesions were larger in lungs of rats exposed to ozone plus ammonium sulfate. Based on these findings and a review of the literature, a mechanism for ozone-aerosol synergism is proposed. We suggest that the lifetime of free radicals arising from interaction of oxidants such as ozone or nitrogen dioxide with molecules within the lung is increased by either local pH changes or changes in the local sulfate concentration (or both) caused by inhalation of the respirable aerosol.

Periodic acid-Schiff (PAS)-positive small-granule endocrine cells identified in serial plastic sections through 95% of the infracardiac lobe of a Syrian golden hamster lung were marked on a 70X cardboard reconstruction of the airways and recorded for computerized analysis as described in the preceding paper in this volume [1]. When airways were subdivided into thirds and the resulting small pieces of airway surface were analyzed statistically, endocrine cell loci appeared to be randomly distributed in the epithelial layer. Nevertheless, loci were absent from only 10 of 209 unit airways, far short of the 28 predicted from a random distribution. Solitary endocrine cells accounted for 37% of 980 loci but only 6% of all endocrine cells; 63% of loci consisted of endocrine cell clusters, broadly defined as "neuroepithelial bodies," of from 2 to 107 cells. Although small groups were preponderant, no significant discontinuity occurred in the size distribution between 1 and 56 cells per locus. Neuroepithelial bodies predominated everywhere, but especially in the lobar bronchus and at bronchioloalveolar portals, where cuboidal bronchiolar epithelium gives way to the attenuated epithelium of the respiratory zone; 45% were related to peribronchial smooth muscle and 18% to pulmonary capillaries. Only 3.3% of solitary cells were related to capillaries, 29% to airway muscle; 68% occurred in muscle-free regions of the airway, associated preferentially with ciliated epithelial cells. We conclude that endocrine cells are distributed in such a way that virtually all airways have at least one locus. This nonrandomness suggests that these cells are in fact important to normal lung function. Furthermore, because solitary endocrine cells and "neuroepithelial" cell clusters have different intrapulmonary distributions, they may well have distinct identities and functions.

The ability of the lung to mechanically remove inhaled deposited particles is an important mammalian defense mechanism that can be evaluated in the laboratory. Experiments that measure clearance kinetics have been performed by various investigators using human as well as large and small laboratory animals as subjects. Several agents have been shown to significantly alter clearance phenomena in the lung. This paper describes quantitative clearance experiments that used radioactive tracer particles to assess lung damage after exposure of rats to ozone, a photochemical air-pollutant gas. Radioactively labeled tracer microspheres were inhaled by groups of 30 rats prior to exposure to ozone. Ozone levels studied were 0.4, 0.8, and 1.0 ppm and all exposures were 4 hr in length. These exposures caused a delay in the early (0-50 hr postdeposition) clearance and an acceleration in the late (50-300 hr postdeposition) clearance rate of the tracer particles. Dose response curves show that clearance was affected more by the higher concentrations of ozone. © 1981 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.