No abstract

Late diagnosis limits therapeutic options and survival rate of non-small cell lung cancer (NSCLC) patients. Therefore the identification of biomarkers represents an emerging medical need.A highly sensitive and specific test was developed to identify/quantify a novel/selective diagnostic biomarker for NSCLC patients, caspase-4. This test was validated by using i) plasma from 125 NSCLC patients and 79 healthy (non-pathological) subjects, ii) plasma from 139 smokers and iii) from 70 chronic-obstructive pulmonary disease (COPD) patients. Caspase-4 quantification was also assessed in the lung tumor mass of 98 paired NSCLC patients compared to 10 non-tumor lung tissues (i.e. tuberculosis).Circulating caspase-4 was detected in both healthy and NSCLC patients; however at different range values: 2.603–3.372 ng/ml for NSCLC patients (95% CI) compared to 0.3994-0.6219 ng/ml for healthy subjects (95% CI). The sensitivity of the test ranged from 97.07% to 100%; the specificity was 88.1% with a positive predictive value of 92.54%, accuracy of 95.19% and AUC of 0.971. Smokers (95% CI, 0.3947–0.6197 ng/ml) and COPD patients (95% CI, 1.703–2.995 ng/ml) showed intermediate values of circulating caspase-4. Tissue levels of caspase-4 in the tumor mass showed that 72 (72.7%) out of 99 patients were positive. More importantly, higher levels (cut-off value = 0.307 ng/ml) of caspase-4 in the tumor mass were associated to reduced overall survival (median 0.92 years) compared to NSCLC patients with lower levels (median 3.02 years).We report for the first time caspase-4 as a novel diagnostic and prognostic biomarker, opening new therapeutic perspectives for NSCLC patients.

The basal ganglia consist of a variety of subcortical nuclei engaged in motor control and executive functions, such as motor learning, behavioral control, and emotion. The striatum, a major basal ganglia component, is particularly useful for cognitive planning of purposive motor acts owing to its structural features and the neuronal circuitry established with the cerebral cortex. Recent data indicate emergent functions played by the striatum. Indeed, cortico-striatal circuits carrying motor information are paralleled by circuits originating from associative and limbic territories, which are functionally integrated in the striatum. Functional integration between brain areas is achieved through patterns of coherent activity. Coherence belonging to cortico-basal ganglia circuits is also present in Parkinson's disease patients. Excessive synchronization occurring in this pathology is reduced by dopaminergic therapies. The mechanisms through which the dopaminergic effects may be addressed are the object of several ongoing investigations. Overall, the bulk of data reported in recent years has provided new vistas concerning basal ganglia role in the organization and control of movement and behavior, both in physiological and pathological conditions. In this review, basal ganglia functions involved in the organization of main movement categories and behaviors are critically discussed. Comparatively, the multiplicity of Parkinson's disease symptomatology is also revised.

SMMs are uncommon but not negligible in lung cancer, with an estimated prevalence of 2.62% in our series. Although histology remains the recommended method, use of high-performance imaging techniques and increased clinical suspicion may improve their early detection. Efforts addressing their effect on the natural history of lung cancer are needed.

AimTo evaluate whether the histology and grading of solitary pulmonary nodules (SPNs) correlated with the results of dynamic multiphase multidetector CT (MDCT) and the [18F]fluorodeoxyglucose standardised uptake value (SUV) in 30 patients.MethodsChest x-rays of 270 patients with incidentally detected SPNs were retrospectively evaluated. Thirty patients with histologically proven SPNs were enrolled. On MDCT and positron emission tomography (PET)/CT images, two experts measured the density of nodules in all perfusion phases and the SUV. Net enhancement (NE) was calculated by subtracting peak pre-contrast density from peak post-contrast density. The Pearson test was used to correlate nodule NE, SUV, grading, histology and diameter.ResultsOf the 30 malignant SPNs, six were classified as G1 (median NE, 31.5 Hounsfield units (HU); median SUV, 4.8 units), 15 were classified as G2 (median NE, 49 HU; median SUV, 6 units), and nine were classified as G3 (median NE, 32 HU; median SUV, 4.5 units). A highly negative correlation was found in G3 SPNs between NE and the corresponding diameters (r=−0.834; p=0.00524). NE increased with the increase in diameter (r=0.982; p=0.284). SUV increased as the SPN diameter increased (r=0.789; p=0.421). NE and SUV were higher in G2 than G1 SPNs, and lower in G2 than G3 SPNs (r=0.97; p=0.137).ConclusionsThe significant correlation in dedifferentiated (G3) SPNs between NE and diameter (r=−0.834; p=0.00524) supports the theory that stroma and neoangiogenesis are fundamental in SPN growth. The highly negative correlation between NE and diameter demonstrates a net decrease in perfusion despite an increase in dimension. The multidisciplinary approach used herein may result in a more precise prognosis and consequently a better therapeutic outcome, particularly in patients with undifferentiated lung cancer.