PubMed · 15397912
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O GORGENYI-GOTTCHE. 1949. About Epituberculosis.. https://pubmed.ncbi.nlm.nih.gov/15397912/
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c-Jun N-terminal kinase (JNK) has been reported to either potentiate or inhibit oncogenesis, depending upon the cellular context, but its role in lung neoplasia is unclear. Here we sought to define the role of JNK in lung neoplasia by examining evidence of JNK phosphorylation in non-small-cell lung cancer (NSCLC) biopsy samples and by using genetic and pharmacologic approaches to modulate JNK expression and activity in cultured cells. Immunohistochemical staining for JNK phosphorylation was detected in 114 (45%) of 252 NSCLC biopsy samples and was predominantly nuclear, providing evidence of JNK activation in a subset of NSCLC cases. Introduction of a doxycycline-inducible, constitutively active, mutant mitogen-activated protein kinase kinase 4 (MKK4) into the human bronchial epithelial cell lines BEAS-2B and HB56B increased the cells' proliferation, migration, invasion and clonogenicity. Depletion of JNK in MKK4 mutant-transformed BEAS-2B cells by introduction of JNK1/2 short hairpin RNA reversed the transformed phenotype, indicating that JNK activation is oncogenic and MKK4 confers neoplastic properties in these cells. The proliferation of NSCLC cell lines HCC827 and H2009, in which JNK and its substrate c-Jun are constitutively phosphorylated, was inhibited by SP600125, a JNK kinase inhibitor. We conclude that JNK is activated in a subset of NSCLC biopsy samples and promotes oncogenesis in the bronchial epithelium, suggesting that strategies to inhibit the JNK pathway should be considered for the prevention and treatment of NSCLC.
BACKGROUND: Foreign body aspiration is common in children, especially those under 3 years of age. Chest radiography and CT are the main imaging modalities for the evaluation of these children. Management of children with suspected foreign body aspiration (SFBA) mainly depends on radiological findings. OBJECTIVE: To investigate the potential use of low-dose multidetector CT (MDCT) and virtual bronchoscopy (VB) in the evaluation and management of SFBA in children. MATERIALS AND METHODS: Included in the study were 37 children (17 girls, 20 boys; age 4 months to 10 years, mean 32 months) with SFBA. Chest radiographs were obtained prior to MDCT in all patients. MDCT was performed using a low-dose technique. VB images were obtained in the same session. Conventional bronchoscopy (CB) was performed within 24 h on patients in whom an obstructive abnormality had been found by MDCT and VB. RESULTS: Obstructive pathology was found in 16 (43.25%) of the 37 patients using MDCT and VB. In 13 of these patients, foreign bodies were detected and removed via CB. The foreign bodies were located in the right main bronchus (n = 5), in the bronchus intermedius (n = 6), in the medial segment of the middle lobe bronchus (n = 1), and in the left main bronchus (n = 1). In the remaining three patients, the diagnosis was false-positive for an obstructive pathology by MDCT and VB; the final diagnoses were secretions (n = 2) and schwannoma (n = 1), as demonstrated by CB. In 21 patients in whom no obstructive pathology was detected by MDCT and VB, CB was not performed. These patients were followed for 5-20 months without any recurrent obstructive symptomatology. CONCLUSIONS: Low-dose MDCT and VB are non-invasive radiological modalities that can be used easily in the investigation of SFBA in children. MDCT and VB provide the exact location of the obstructive pathology prior to CB. If obstructive pathology is depicted with MDCT and VB, CB should be performed either for confirmation of the diagnosis or for the diagnosis of an alternative cause for the obstruction. In cases where no obstructive pathology is detected by MDCT and VB, CB may not be clinically useful.
Mechanical strain of lung tissue is an important stimulus for the production of growth factors that are critical for lung growth and development. However, excessive mechanical strain, as may occur during mechanical ventilation, may produce an increase in growth factors that may contribute to lung injury. We hypothesized that mechanical strain of primary bronchial airway epithelial cells (BAEpCs) induced the production of placental growth factor (PlGF), a member of the VEGF family. BAEpCs were cultured on a deformable silicoelastic membrane and exposed to different magnitudes of stretch. Stretch induced PlGF and nitric oxide (NO) production that increased with increasing magnitude of stretch. Stretch also induced PlGF and inducible NO synthase (iNOS) gene expression. The stretch-induced PlGF production and NO synthesis were attenuated by PD98059, a specific mitogen-activated protein kinase kinase-1 and -2 inhibitor. Inhibition of NO generation by l-NAME or l-NMMA or scavenging NO by carboxy-PTIO prevented stretch-mediated erk1/2 activation. In addition, in unstretched BAEpCs, exogenous NO enhanced erk1/erk2 activation. Our data suggest that mechanical stretch of BAEpCs induces iNOS expression and induces PlGF release in an erk1/2 activation-dependent manner.