Aberrant vascularization is a hallmark of cancer progression and treatment resistance. Here, we have shown that endothelial cell (EC) plasticity drives aberrant vascularization and chemoresistance in glioblastoma multiforme (GBM). By utilizing human patient specimens, as well as allograft and genetic murine GBM models, we revealed that a robust endothelial plasticity in GBM allows acquisition of fibroblast transformation (also known as endothelial mesenchymal transition [Endo-MT]), which is characterized by EC expression of fibroblast markers, and determined that a prominent population of GBM-associated fibroblast-like cells have EC origin. Tumor ECs acquired the mesenchymal gene signature without the loss of EC functions, leading to enhanced cell proliferation and migration, as well as vessel permeability. Furthermore, we identified a c-Met/ETS-1/matrix metalloproteinase-14 (MMP-14) axis that controls VE-cadherin degradation, Endo-MT, and vascular abnormality. Pharmacological c-Met inhibition induced vessel normalization in patient tumor-derived ECs. Finally, EC-specific KO of Met inhibited vascular transformation, normalized blood vessels, and reduced intratumoral hypoxia, culminating in suppressed tumor growth and prolonged survival in GBM-bearing mice after temozolomide treatment. Together, these findings illustrate a mechanism that controls aberrant tumor vascularization and suggest that targeting Endo-MT may offer selective and efficient strategies for antivascular and vessel normalization therapies in GBM, and possibly other malignant tumors.

Background: Immunotherapy is effective in treating unresectable esophageal squamous cell carcinoma (ESCC), but little is known about its role in the preoperative setting. The aim of this study was to evaluate the safety, feasibility and efficacy of neoadjuvant treatment with camrelizumab plus chemotherapy in locally advanced ESCC.Methods: Patients diagnosed with locally advanced ESCC were retrospectively included if they had received neoadjuvant camrelizumab plus nab-paclitaxel and S1 capsule followed by radical esophagectomy between November, 2019 and June, 2020 at Sun Yat-sen University Cancer Center. Primary endpoints were safety and feasibility. In addition, pathological response and the relationship between tumor immune microenvironment (TIME)/tumor mutational burden (TMB) and treatment response were also investigated.Results: Twelve patients were included and they all received three courses of preoperative treatment with camrelizumab plus nab-paclitaxel/S1. No grade 3 or higher toxicities occurred. No surgical delay or perioperative death was reported. Nine patients (75%) responded to the treatment, four with a complete pathological response (pCR) and five with a major pathological response (MPR). Neither programmed death-ligand 1 (PD-L1) expression nor TMB was correlated with treatment response. TIME analysis revealed that a higher abundance of CD56dim natural killer cells was associated with better pathological response in the primary tumor, while lower density of M2-tumor-associated macrophages was associated with better pathological response in the lymph nodes (LNs).Conclusions: Neoadjuvant camrelizumab plus nab-paclitaxel and S1 is safe, feasible and effective in locally advanced ESCC and is worth further investigation.

Radiation encephalopathy (RE) is one of the most severe complications in nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT). However, the morphological alteration of early RE is insufficiently investigated. We aimed to investigate the cortical thickness and surface area alterations in NPC patients with or without RE in the follow-up. A total of 168 NPC patients each underwent a single scan and analysis at various times either Pre-RT (n = 56) or Post-RT (n = 112). We further divided the Post-RT NPC patients into three groups based on the time of the analysis following RT (Post-RTwithin 6 months and Post-RT7-12 months) or whether RE signs were detected in the analysis (Post-RTRE proved in follow-up). We confined the vertex-wise analyses of the cortical thickness and surface area to the bilateral temporal lobes. Interestingly, we revealed a gradual increase in the cortical surface area of the temporal lobe with increasing time after RT within the Post-RTRE proved in follow-up group, consistent with the between-group findings, which showed a significant increase in cortical surface area in the Post-RTRE proved in follow-up group relative to the Pre-RT group and the Post-RTwithin 6 months group. By contrast, such a trend was not observed in the cortical thickness findings. We concluded that the cortical surface area, rather than cortical thickness, may serve as a potential biomarker for early diagnosis of RE.

EWS/PNETs in the anterior and middle mediastinum appear as ill-defined, heterogenerous masses that are not distinguishable from other, more common, causes of mediastinal masses, based on their CT features.

Primary duodenal GISTs are generally large, well-defined, heterogeneously enhancing, and hypervascular masses with a prominent mixed growth pattern on CT images. Our findings suggest that CT can help depict the origin of the tumoral arteries and draining veins on the arterial phase and may be a key defining diagnostic feature for duodenal GISTs.