Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT , AKT1 , PIK3CA , and EIF1AX were frequently co-mutated with driver genes ( BRAF V600E and RAS ) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A ) were predominantly altered in ATC. CDKN2A loss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation of CD274 (PD-L1) and PDCD1LG2 (PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target in RAS -positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.

Considering the low incidence of regional lymph node recurrence and the levels with frequent regional recurrence in patients without lymph node metastasis, elective neck dissection in all cases of total thyroidectomy may be immoderate. However, if any risk factors for regional recurrence, including large tumor size, presence of extrathyroid spread, high T stage, and presence of lymph node metastasis, are detected by preoperative and intraoperative evaluation, a systematic compartment-oriented lymphadenectomy should be considered because of the high possibility of regional recurrence.

BackgroundHybrid scaffolds combining biodegradable polymers and ceramic particles for control of cell adhesion and proliferation are interesting materials for tissue engineering applications. Combinations of biodegradable polymers and ceramics are to provide higher beneficial functionalities to tissue engineering scaffolds with addition of different cell specific bio-factors. Many such hybrid combinations have been reported by several researchers around the world by using various methods and solvents as well as bioactive matrix polymers to fabricate such biomaterials. However, thin hybrid scaffolds with high porosity, cell adhesion factors and biodegradability, as well as the ability to support stem cells often require tedious processes like electrospinning, freeze drying, etc. A simple method to develop porous biodegradable hybrid scaffolds with proper cell adhesion factors is still the need of the hour in tissue engineering and regenerative medicine.MethodThin biodegradable poly(ε-caprolactone) (PCL) based hybrid scaffolds were developed in combination with α-tricalcium phosphate (TCP) particles, gelatin and fibronectin separately and the fabricated scaffolds were evaluated systematically using human mesenchymal stem cells (hMSCs) for tissue engineering applications. A simple modified solvent casting method combined with gas foaming process was used to develop porous thin hybrid structures and compared their properties with those of corresponding non-porous hybrid scaffolds. The TCP particles distribution, morphology, biodegradability and functional groups of the different hybrid scaffolds were analyzed using energy-dispersive X-ray spectroscopy (EDX), light microscopy/scanning electron microscopy (SEM), buffer solutions and Fourier-transform infrared spectroscopy (FTIR), respectively The cellular and tissue regeneration behaviors such as in vitro cell attachment (live/dead assay), cell proliferation (CCK-8 assay) and histological studies were performed using hMSCs.ResultsThin PCL-based hybrid scaffolds were fabricated using modified solvent casting method. Homogeneous distribution of TCP particles in the scaffolds were confirmed by EDX. Cellular interactions of the hybrid scaffolds demonstrated overall higher cell adhesion, proliferation and tissue regeneration on the non-porous thin films of PCL-TCP, PCL-TCP-gelatin and PCL-TCP-fibronectin. Coating of fibronectin was remarkable in induction of cell adhesion and proliferation.ConclusionsThe experimental results revealed that diversely designed PCL-TCP thin hybrid films showed high cell interaction and proliferation with hMSCs. From the results of the cell viability, attachment, proliferation and histological analyses as well as their biodegradation and coating effects, we conclude that these thin PCL-TCP hybrid films are suitable for tissue engineering applications.

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Programmed death-ligand 1 (PD-L1) expression is regarded as a predictive marker for anti-PD-1/PD-L1 therapy. The purpose of study was to explore the changes in PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) during treatment. Paired HNSCC tissues prior to and after cisplatin-based treatment were evaluated to determine PD-L1 protein expression by immunohistochemistry. Among the 35 HNSCC patient samples, PD-L1 expression status changed after treatment in 37.1% (13/35) of samples. Among the 13 patients whose baseline PD-L1 was negative, PD-L1 expression was increased in 9 cases (69.2%) and remained negative in 4 cases (30.8%, P = 0.003). Patients exposed to cisplatin generally showed PD-L1 up-regulation (83.3%, P = 0.037) compared to those not exposed to cisplatin (57.1%, P = 0.072). To validate these findings in vitro, changes in PD-L1 expression in HNSCC cell lines (Detroit-562, PCI-13, SNU-1041, SNU-1066, SNU-1076, and FaDu) were analyzed by western blotting and flow cytometry after treatment with cisplatin and interferon-gamma. In HNSCC cell lines, PD-L1 expression was significantly up-regulated after cisplatin, along with phosphor-MAPK/ERK kinase up-regulation. In conclusion, PD-L1 expression in HNSCC may be altered during cisplatin treatment, activating the MAPK/ERK kinase pathway.