The detection of molecular alterations is crucial for the individualized treatment of advanced non-small cell lung cancer (NSCLC). Missing targetable alterations may have a major impact on patient’s progression free and overall survival. Although laboratory testing for molecular alterations has continued to improve; little is known about how biopsy technique affects the detection rate of different mutations. In the retrospective study detection rate of epidermal growth factor (EGFR) mutations in tissue extracted by bronchoscopic cryobiopsy (CB was significantly higher compared to other standard biopsy techniques. This prospective, randomized, multicenter, single blinded study evaluates the accuracy of molecular genetic characterization of NSCLC for different cell sampling techniques. Key inclusion criteria are suspected lung cancer or the suspected relapse of known NSCLC that is bronchoscopically visible. Patients will be randomized, either to have a CB or a bronchoscopic forceps biopsy (FB). If indicated, a transbronchial needle aspiration (TBNA) of suspect lymph nodes will be performed. Blood liquid biopsy will be taken before tissue biopsy. The primary endpoint is the detection rate of molecular genetic alterations in NSCLC, using CB and FB. Secondary endpoints are differences in the combined detection of molecular genetic alterations between FB and CB, TBNA and liquid biopsy. This trial plans to recruit 540 patients, with 178 evaluable patients per study cohort. A histopathological and molecular genetic evaluation will be performed by the affiliated pathology departments of the national network for genomic medicine in lung cancer (nNGM), Germany. We will compare the diagnostic value of solid tumor tissue, lymph node cells and liquid biopsy for the molecular genetic characterization of NSCLC. This reflects a real world clinical setting, with potential direct impact on both treatment and survival.
lower than that for both of these agents added sequentially. Interestingly, when the sequence of addition of drugs was reversed using 5azaD/SAHA, the reduction in growth (66% vs. 85%, P , 0.05) and percentage of apoptotic cells were lower than in cultures treated with SAHA/5azaD. The greatest amount of glioma cell death induced by SAHA/5azaD corresponded with higher protein levels of the cyclin dependent kinase inhibitor, P 21 , and the minimum fraction of cells in active phases of cell cycle (19% in control vs. 11% in SAHA/5azaD). Furthermore, glioma cells treated with SAHA/ 5azaD or 5azaD/SAHA displayed the highest levels of acetylated histone H4 protein levels, indicating possible epigenetic changes. Our data indicating that the effects of SAHA/5azaD are likely mediated by epigenetic mechanisms is made evident by increases in P 21 and acetylated histone H4 protein levels. Whether such strategies are also effective in primary human glioma tumor cells will be tested, which may ultimately open untapped territories to search for curative therapies.
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