Changes in Indoleamine 2,3-Dioxygenase 1 Expression and CD8+ Tumor-Infiltrating Lymphocytes after Neoadjuvant Chemoradiation Therapy and Prognostic Significance in Esophageal Squamous Cell Carcinoma.

PURPOSE: Despite good preclinical evidence, clinical data on the effect of neoadjuvant chemoradiation therapy (CRT) on expression of immune markers in esophageal cancer are limited. This study aimed to evaluate the changes in indoleamine 2,3-dioxygenase 1 (IDO1) expression, programmed cell death-ligand 1 (PD-L1) expression, and CD8+ tumor-infiltrating lymphocyte status after neoadjuvant CRT and the prognostic significance in esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: Between 2003 and 2017, 138 patients with ESCC who underwent neoadjuvant CRT and esophagectomy without achieving pathologic complete response were included for analysis. Both pre-CRT biopsies and post-CRT surgical specimens were available in 82 patients. Immunohistochemistry of IDO1, PD-L1, and CD8 density were analyzed. RESULTS: Among 82 paired samples, the expression levels of IDO1 and PD-L1 and CD8 density increased significantly after neoadjuvant CRT (P < .01 for all). Patients with high IDO1 expression after CRT had poorer overall survival (P = .001) and recurrence-free survival (P < .001) than those with low IDO1 expression. High post-CRT CD8 density was significantly correlated with more favorable overall survival (P = .01) and recurrence-free survival (P = .008). Neither pre- nor post-CRT PD-L1 expression was an independent prognostic factor for survival. Stratification analysis revealed that patients with combined low IDO1 expression and high CD8 density after CRT were significantly associated with better survival than other subgroups. The major findings were reproducible in an independent validation cohort. CONCLUSIONS: IDO1 and PD-L1 expression and CD8 density increased significantly after neoadjuvant CRT in ESCC. The post-CRT IDO1 expression and CD8 density could serve as prognostic biomarkers for survival.

Improvement of ZrC/Zr Coating on the Interface Combination and Physical Properties of Diamond-Copper Composites Fabricated by Spark Plasma Sintering.

In this study, diamond-copper composites were prepared with ZrC/Zr-coated diamond powders by spark plasma sintering. The magnetron sputtering technique was employed to coat the diamond particles with a zirconium layer. After heat treatment, most of the zirconium reacted with the surface of diamond and was transformed into zirconium carbide. The remaining zirconium on the zirconium carbide surface formed the outer layer. Owing to the method used to produce the ZrC/Zr-coated diamond in this study, the maximum thermal conductivity (TC) of 609 W·m-1·K-1 was obtained for 60 vol. % diamond-copper composites and the corresponding coefficient of thermal expansion (CTE) reached as low as 6.75 × 10-6 K-1. The bending strength of 40 vol. % ZrC/Zr-coated diamond-copper composites reached 255.95 MPa. The thermal and mechanical properties of ZrC/Zr-coated diamond-copper composites were substantially superior to those of uncoated diamond particles. Excellent properties can be attributed to the strengthening of the interfacial combination and the decrease in the interfacial thermal resistance due to the improvement associated with the ZrC/Zr coating. Theoretical analysis was also proposed to compare the thermal conductivities and CTE of diamond-copper composites fabricated with these two kinds of diamond powders.

[Effect of siRNA targeting PML-RARa fusion gene on activity of the acute promyelocytic leukemia cell line NB4].

This study aims to investigate the effects of small interference RNA (siRNA) targeting PML-RARa mRNA on the activity of the acute promyelocytic leukemia cell line NB4. The proliferation inhibition was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry after siRNA treatment. The results showed that the cell growth of siRNA treated group was inhibited, and the apoptosis of NB4 could be induced. The siRNA targeting PML-RARα mRNA might be a valid therapy of acute promyelocytic leukemia.