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Patients with non-small cell lung cancer, especially adenocarcinomas, harbour at least one oncogenic driver mutation that can potentially be a target for therapy. Treatments of these oncogene-addicted tumours, such as the use of tyrosine kinase inhibitors (TKIs) of mutated epidermal growth factor receptor, have dramatically improved the outcome of patients. However, some patients may acquire resistance to treatment early on after starting a targeted therapy. Transformations to other histotypes—small cell lung carcinoma, large cell neuroendocrine carcinoma, squamous cell carcinoma, and sarcomatoid carcinoma—have been increasingly recognised as important mechanisms of resistance and are increasingly becoming a topic of interest for all specialists involved in the diagnosis, management, and care of these patients. This article, after examining the most used TKI agents and their main biological activities, discusses histological and molecular transformations with an up-to-date review of all previous cases published in the field. Liquid biopsy and future research directions are also briefly discussed to offer the reader a complete and up-to-date overview of the topic.  相似文献   
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Coconut sugar is traditionally produced by evaporating sap until reaching its saturated liquid and formed a crystalline structure. This study investigated the comparison of coconut sugar made by traditional method (crystalline structure) and dried coconut sugar (predominantly amorphous structure) to its characteristics. Two different formulation of coconut sap : maltodextrin (7 : 3) and (6 : 4) (weight/weight) were dried using vacuum oven (70℃, 6 hours) and spray dried (Tinlet 120℃.) Coconut sugar was characterized for moisture content, crystallinity, water sorption isotherm, hygroscopic rate, color, dissolving time, and powder recovery. Initial moisture content was examined and in range of 1.33% - 3.44% (wb). The highest monolayer water content was obtained by using spray drying (6 : 4) and lowest was obtained by traditional method. X-ray diffraction showed that dried coconut sugar powder had dominant amorphous structure (70.9 – 71.4%) while traditional one was dominated with crystalline structure (90.5%). Traditional coconut sugar was the least hygroscopic (1.21 × 10-4 g water/g solid/minutes), followed by vacuum dried coconut sugar (1.48 × 10-4 g water/g solid/minutes) and spray dried ones (1.56 – 1.67 × 10-4 g water/g solid/minutes). Spray dried coconut sugar had the brightest and the whitest color, followed by vacuum dried and traditional coconut sugar. Vacuum dried powder was quicker to dissolve (13.33 – 16.67 s), while increasing maltodextrin in spray drying could not decrease the dissolving time. The highest powder recovery of dried sugar was obtained by using vacuum drying and higher maltodextrin concentration (88.70%) while traditional method produced 100% powder recovery.  相似文献   
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