Although EGFR mutant-selective TKIs are clinically effective, acquired resistance can occur by reactivating ERK. We show using in vitro models of acquired EGFR TKI resistance with a mesenchymal phenotype that CXCR7, an atypical GPCR, activates the MAPK-ERK pathway via β-arrestin. Depletion of CXCR7 inhibited the MAPK pathway, significantly attenuated EGFR TKI resistance and resulted in mesenchymal to epithelial transition. CXCR7 overexpression was essential in reactivation of ERK1/2 for the generation of EGFR TKI resistant persister cells. Many NSCLC patients harboring an EGFR kinase domain mutation, who progressed on EGFR inhibitors, demonstrated increased CXCR7 expression. These data suggest that CXCR7 inhibition could considerably delay and prevent the emergence of acquired EGFR TKI resistance in EGFR mutant NSCLC.Becker et al.

BACKGROUND.The objective of this study was to investigate the diagnostic value of methylation profiles for discrimination between malignant and benign pleural effusions. A secondary objective was to examine the concordance of methylation in samples of serum and pleural fluid.METHODS.The authors used methylation‐specific polymerase chain reaction (MSP) analysis to examine the promoter methylation status of 4 genes in patients with pleural effusion: death‐associated protein kinase (DAPK), Ras association domain family 1A (RASSF1A), retinoic acid receptor β (RARβ), and p16/INK4a. Pleural effusions were collected from 87 patients who had their diagnoses confirmed on cytologic and/or histologic examinations and clinical evolution. Pleural effusions were classified as malignant (n = 53 patients) or benign (n = 34 patients).RESULTS.Methylation was detected in serum from 45.3% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions, and it was detected in pleural fluid samples from 58.5% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions (P = .001). The sensitivity of MSP was greater than that of cytologic examination alone (39.1%; P = .001). When MSP was used together with cytologic examination, sensitivity increased to 69.8% (P = .001).CONCLUSIONS.Cell‐free methylated DNA in pleural fluid can be detected in patients with neoplastic malignancy in a single extraction by thoracocentesis. Adequate management of the extracted pleural fluid can provide a rapid and reliable diagnosis in patients with pleural effusions who have suspected malignancy. MSP, used together with cytologic examination, may obviate the need for other invasive diagnostic tests. Cancer 2006. © 2006 American Cancer Society.

Quantitative real-time RT-PCR of CEACAM5 and PLUNC can estimate the presence of micrometastatic cells in LNs with greater precision than current staging method used for assessing tumor recurrence risk.

No abstract

There is no other system that allows repeated venous access on such a long term basis. Placing the devices completely under the skin allows the patient to conduct a normal life style, and its maintenance does not need any special care, with the exception of the monthly heparinised serum infusion. The preferred option is to insert the catheter through the cephalic vein in the delto pectoral groove.

Endotracheal metastases (ETM) from non-lung cancer are seldom seen. Their main clinical symptoms are cough, haemoptysis and dyspnoea, although occasionally an incidental finding is made during a bronchoscopy. Breast, colon and kidney adenocarcinoma might be associated with ETM, lung cancer being the most frequent cause. Its finding is associated with advanced disease but survival will depend on the primary origin, patient status and comorbidity. Therefore, treatment should be individual for each patient. In our centre we recommend pre-surgery bronchoscopy to exclude metastatic endotracheal lesions in patients with metastatic colon adenocarcinoma disease, as this might affect the final outcome and therefore management of the disease.

The ideal tracheal substitute must have biomechanical properties comparable to the native trachea, but currently there is no standardised approach to evaluating these properties. Here we propose a novel method for evaluating and comparing the properties of tracheal substitutes, thus systematising both measurement and data curation. This system was tested by comparing native rabbit tracheas to frozen and decellularised specimens and determining the histological characteristics of those specimens. We performed radial compression tests on the anteroposterior tracheal axis and longitudinal axial tensile tests with the specimens anastomosed to the jaw connected to a measuring system. All calculations and results were adjusted according to tracheal size, always using variables relative to the tracheal dimensions, thus permitting comparison of different sized organs. The biomechanical properties of the decellularised specimens were only slightly reduced compared to controls and significant in regard to the maximum stress withstood in the longitudinal axis (−0.246 MPa CI [−0.248, −0.145] MPa) and the energy stored per volume unit (−0.124 mJ·mm−3 CI [−0.195, −0.055] mJ·mm−3). The proposed method is suitable for the systematic characterisation of the biomechanical properties of different tracheal substitutes, regardless of the size or nature of the substitute, thus allowing for direct comparisons.

Wide resection of sternal tumours provides good local control. Reconstruction with mesh and musculocutaneous flap is an effective technique for repairing such defects.