The down-regulation of the catalytic subunit of the mitochondrial H + -ATP synthase (B-F1-ATPase) is a hallmark of most human carcinomas. This characteristic of the cancer cell provides a proteomic signature of cellular bioenergetics that can predict the prognosis of colon, lung, and breast cancer patients. Here we show that the in vivo tumor glucose uptake of lung carcinomas, as assessed by positron emission tomography in 110 patients using 2-deoxy-2-[18 F]fluoro-D-glucose as probe, inversely correlates with the bioenergetic signature determined by immunohistochemical analysis in tumor surgical specimens. Further, we show that inhibition of the activity of oxidative phosphorylation by incubation of cancer cells with oligomycin triggers a rapid increase in their rates of aerobic glycolysis. Moreover, we show that the cellular expression level of the B-F1-ATPase protein of mitochondrial oxidative phosphorylation inversely correlates (P < 0.001) with the rates of aerobic glycolysis in cancer cells. The results highlight the relevance of the alteration of the bioenergetic function of mitochondria for glucose capture and consumption by aerobic glycolysis in carcinomas. [Cancer Res 2007;67(19):9013-7]

Purpose: Activating somatic mutations in the epidermal growth factor receptor (EGFR) gene are present in a small subset of lung adenocarcinomas.These mutations cluster in specific regions and confer sensitivity to inhibitors of the tyrosine kinase activity of EGFR. To further determine the genetic and molecular characteristics of tumors carrying EGFR gene mutations, we investigated the EGFR gene status in lung adenocarcinomas and evaluated its association with specific characteristics of the patients and tumors, such as mutations at KRAS and p53, EGFR and ErbB2 gene amplification, levels of EGFR and HER2 proteins, and levels of downstream effectors of EGFR, such as phospho^extracellular signal-regulated kinase and phospho-S6 proteins. Experimental Design: The mutational status of EGFR was determined by direct sequencing in 86 primary lung adenocarcinomas and12 lung cancer cell lines, and was correlated with a number of variables relating to the tumor and patient. A tissue microarray containing 37 lung tumors was constructed to determine, by fluorescence in situ hybridization analysis, the number of copies of EGFR and ErbB2 genes and, by immunohistochemistry, the levels of EGFR, HER2, phospho-ERK, and phospho-S6 proteins. Results: EGFR gene mutations were identified in 13% of the primary tumors. The type and clustering of the mutations were identical to those previously reported. Amplification of the EGFR occurred in14% of the tumors and could arise in tumors with EGFR mutations. Interestingly, mTOR activation, as measured indirectly by augmented levels of phospho-S6 protein, was more frequent in tumors with gene alterations in either EGFR or KRAS (P = 0.00005; Fisher's exact test) than in their wild-type counterparts. Conclusions: Our data agree with the accumulation of EGFR mutations in a subset of patients with lung cancer. Moreover, we report EGFR gene amplification in EGFR-mutant tumors and a positive correlation between EGFR or KRAS alterations and activation of mTOR signaling.

The development of targeted therapies creates a need to discriminate tumours accurately by their histological and genetic characteristics. Here, we aim to identify gene expression profiles and single markers that recapitulate the pathological and genetic background of non-small cell lung cancer (NSCLC). We performed cDNA microarray analysis on a series of 69 NSCLCs, with known mutation status for important genes, and six normal lung tissues. Unsupervised cluster analysis segregated normal lungs from lung tumours and lung tumours according to their histopathology and the presence of EGFR mutations. Several transcripts were highly overexpressed (by approximately 20 times) in squamous cell carcinomas (SCCs) relative to adenocarcinomas (ACs) and confirmed by immunohistochemistry in an independent cohort of 75 lung tumours. Expression of 13 genes constituted the most prominent hallmarks of EGFR-mutant tumours, including increased levels of proline dehydrogenase (PRODH) and down-regulation of X-box binding protein 1 (XBP1). No genes were differentially expressed, with a fold change >or= 4 or

The aim of therapeutic thoracentesis (TT) is to aspirate as much pleural fluid as possible. Monitoring pleural pressure (PlP) during TT has been proposed to avoid the adverse effects due to an unintended sharp drop in PlP. The objectives of this study are to ascertain the diagnostic value of the PlP measurement, to find a predictive variable of the amount of fluid that can be removed, to obtain insight into the characteristics of the PlP curve and pleural elastance (PE) during TT, and to describe the complications of TT. Sixty-one unselected patients were studied. Only the four patients with suspected trapped lung had an initial PlP lower than -4 cm H(2)O and a PE higher than 33 cm H(2)O/L. There was a weak correlation (r = 0.52) between PE during the first 0.5 L aspirated and the total amount of fluid aspirated. Partial PE values were 10, 7.5, and 14 cm H(2)O/L at the early, intermediate, and late phases of TT. No complications were found except for nine pneumothoraces. In conclusion, the technique was clinically helpful because large amounts of pleural fluid could be aspirated with few and mild complications, and because it allows clinicians to support the preliminary diagnosis of trapped lung. None of the studied variables was found to predict the suitability of aspirating more than 1.5 L. Rather than being monotonically descendent, the PlP curve shows a three-part line with the deepest slopes at the first and last phases of the thoracentesis.

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hCT and PET perform similarly in the mediastinal staging of NSCLC, both tests are conditionally dependent and provide complementary information, and their diagnostic value mainly resides on the negative results.

The analysis of conditional survival at 24 months shows that COPD can be considered as a prognostic factor and that there is a clear relationship between the severity of the condition (FEV1%) and survival.