No abstract

Expression of RARalpha and RXRalpha is either normal or elevated in NSCLC. In contrast, a large percentage of tumors show a marked decrease in the expression of RARbeta, RARgamma, and RXRbeta as well as a high frequency of LOH at 3p24, which was also observed in non-neoplastic lesions. These data suggest that altered retinoid receptor expression may play a role in lung carcinogenesis.

No abstract

Transglutaminase type 1 (TGase 1) is a member of a class of enzymes that catalyze the cross-linking of proteins, a characteristic feature of epidermal differentiation and squamous metaplasia. The role of TGase 1 has been extensively studied in epidermis but not in the lung. Using a polyclonal anti-TGase 1 antibody prepared in our laboratory (TGase-lac), TGase 1 expression in normal bronchial epithelium, bronchial preinvasive lesions, and lung cancer was characterized. The specificity of the antibody was confirmed by the presence in squamous differentiated bronchial cells of specific 106-kD and 92-kD bands by Western blotting. In addition, immunohistochemistry displayed a recognized pattern of labeling in both normal and tumor cells beneath the cytoplasmic membrane and within the cytosol. TGase 1 was shown to be expressed by cells from bronchial epithelium and bronchial preinvasive lesions, strongly expressed in most non-small-cell lung cancer tumor cells and in apoptotic bodies, but weakly expressed in small-cell lung cancer. The distribution of TGase 1 mRNA correlated with the immunohistochemical profile. These observations suggest that TGase 1 expression is a normal feature of bronchial epithelium and is linked to the process of squamous differentiation occurring in preinvasive lesions. Its role in lung cancer remains to be clarified.

Endobronchial ultrasound-guided transbronchial needle aspiration has demonstrated its accuracy in the diagnostic workup of enlarged mediastinal lymph nodes. In addition to conventional smears, the use of liquid-based cytology (LBC) and cell block preparations (CBP) has been introduced more recently. The aim of our study was to determine the performance of each of the different techniques, separately and combined, in terms of diagnostic yield and sensitivity. A total of 290 consecutive patients were included. The pathological examination was based on smear cytology, LBC, and CBP. Adequate sampling was defined by the presence of pathological material or lymphocytes. The global diagnostic yield was 82.7 % and the sensitivity was 89.1 %. The diagnostic yield was 72.8 % for smears, 78.8 % for LBC, and 69.9 % for CBP. The combination of smears with CBP significantly increased diagnostic yield (p = 0.01) and sensitivity (p = 0.006), but not the combination of smears with LBC (yield: p = 0.07; sensitivity: p = 0.13). The combination of the three techniques further increased yield (p = 0.007) and sensitivity (p = 0.006), compared with smears alone. CBP were more sensitive than smears for both diagnoses of carcinoma (p = 0.01) and granulomatous inflammation (p = 0.048). Conversely, LBC was less sensitive than smears for granulomatous inflammation (p = 0.004), but the difference was not significant for carcinoma (p = 0.42). CBP, as a complement to smears, increases diagnostic yield and sensitivity for both diagnoses of carcinoma and granulomatous inflammation. LBC, if used alone, increases the risk of a false-negative result.

The increase in cerebral blood flow (CBF) elicited by moderate hypoxia in anesthetized animals is little attenuated by nitric oxide (NO) synthase inhibitors. However, in previous studies, the effects of NO synthase inhibitors may have been altered by anesthetics. Consequently, we studied the effects of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on cerebral and myocardial blood flows during hypoxia in the awake dog. Regional CBF and myocardial blood flows (MBF) were measured under normoxia and hypoxia in 16 beagle dogs after an intravenous (IV) injection of either saline (control, n = 8) or L-NAME 20 mg/kg (n = 8). One week after thoracotomy for catheter insertion, awake dogs were studied during three periods: normoxia and after 2 and 4 h of normocapanic hypoxia in an environmental chamber (FIO2 = 0.10, FICO2 = 0.035, balance N2). At each stage, a bolus injection of L-NAME or saline was followed 15 min later by left atrial injection of radiolabeled microspheres (141Ce, 103Ru, 46Sc) for regional CBF and MBF. After the dogs were killed, the brain and the heart were fixed in 10% formaldehyde, dissected by region and weighed, and radioactivity was measured in a gamma counter. During hypoxia, Pao2 was approximately 45 mm Hg with normal Paco2. In the control group, CBF increased by 45% after 2 h and 48% after 4 h of hypoxia; MBF increased by 69% and 60%, respectively. L-NAME prevented the CBF increase during hypoxia and the MBF increase after 2 h of hypoxia; after 4 h of hypoxia the measurement of MBF was confounded by cardiac dysfunction. These results suggest that NO plays a role in cerebral vasodilation during hypoxia in the awake animal.

The prognostic value of EGFR exon 19 and 21 mutations appears to be different according to disease stage in surgically resected NSCLC.

Overall and stage-adjusted survival of operated lung cancer patients has been improved in the last decade due mainly to earlier diagnosis. The generalized use of computed tomography scan, chemotherapy, and a collegial management improved patients' survival.