Superhydrophobic lab-on-chip measures secretome protonation state and provides a personalized risk assessment of sporadic tumour.

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual's diagnosis and/or help clarify risk in healthy populations.

In vitro expansion of tumour cells derived from blood and tumour tissue is useful to redefine personalized treatment in non-small cell lung cancer patients.

The clinical development of locally and advanced non-small cell lung cancer (NSCLC) suffers from a lack of biomarkers as a guide in the selection of optimal prognostic prediction. Circulating Tumour Cells (CTCs) are correlated to prognosis and show efficacy in cancer monitoring in patients. However, their enumeration alone might be inadequate; it might also be critical to understand the viability, the apoptotic state and the kinetics of these cells. Here, we report what we believe to be a new and selective approach to visually detect tumour specific CTCs. Firstly, using labelled human lung cancer cells, we detected a specific density interval in which NSCL-CTCs were concentrated. Secondly, to better characterize CTCs in respect to their heterogeneous composition and tumour reference, blood and tumour biopsy were performed on specimens taken from the same patient. The approach consisted in comparing phenotype profile of CTCs, and their progenitor Tumour Stem Cells, (TSCs). Moreover, NSCL-CTCs were cultivated in short-time human cultures to provide response to drug sensitivity. Our bimodal approach allowed to reveal two items. Firstly, that one part of a tumour, proximal to the bronchial structure, displays a predominance of CD133+. Secondly, specific NSCL-CTCs Epithelial Cell Adhesion Molecule (EpCAM)+CD29+ can be used as a negative prognostic factor as well the high expression of CTCs EpCAM+. These data were confirmed by drug-sensitivity tests, in vitro, and by the survival curves, in vivo.

IIIB-T4 non-small cell lung cancer: indications and results of surgical treatment.

AIM: T4 non-small cell lung cancer (NSCLC) is commonly considered a contraindication to surgery, indeed chemo-radiotherapy achieves a poor survival rate. We have reviewed our experience with T4 NSCLC patients who underwent surgery with the aim of debating the indications and results of surgical treatment in this highly selected group of patients. METHODS: We investigated a cohort of 60 patients, 49 men and 11 women, who underwent surgery for NSCLC from January 1998 to December 2002 and whose pathological staging was T4N0-2M0. The median age was 65 years (range 46-82). The tumors were classified T4 for the following reasons: intralobar satellite metastasis in 24 cases, direct mediastinum invasion in 18 cases, malignant pleural effusion in 7 cases, involvement of the superior vena cava in 4 cases, marginal invasion of the vertebral body in 3 cases, involvement of the carena in 3 cases and invasion of the left atrium in 1 case. Thirteen patients had undergone neo-adjuvant chemotherapy while 39 underwent adjuvant therapies. RESULTS: Thirty-two patients resulted with N0 disease, 5 with N1 and 23 with N2 disease. Forty patients relapsed (27 systemic and 13 local relapses). The mean survival was 20 months. Of the examined parameters only metastatic nodal involvement was significantly associated with a worse prognosis (P=0.007). CONCLUSION: Surgery for T4 NSCLC may be effective in those patients without mediastinal (N2) lymph node involvement. The prognosis was neither affected by the subtype of T4 tumor nor by the use of adjuvant therapies and/or neoadjuvant chemotherapy but only by the N status. In the preoperative work-up, every possible effort should be made to achieve a careful evaluation of lymph-nodal status (primarily by mediastinoscopy and video operative staging).