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Objective: Diffuse large B‐cell lymphoma (DLBCL) can be classified as germinal center B cell–like (GCB) or activated B cell–like (ABC)/non‐GCB based on cell‐of‐origin (COO) classification. This study evaluated the prognostic significance of COO classification in 250 patients diagnosed with de novo DLBCL who received R‐CHOP therapy. We also assessed whether the genomic status of MYC, BCL2, or MYC/BCL2 double expression (DE) could provide additional prognostic information for DLBCL patients. Methods: The clinicopathologic features and outcome of patients with GCB DLBCL were compared to patients with non‐GCB DLBCL using Fisher's exact test. The prognostic significance of COO, MYC‐R, and MYC/BCL2 DE were studied using multivariate Cox proportional hazard analysis. Results: There were 162 men and 88 women with a median age of 62 years (range, 18‐86). Forty‐five of 250 (18%) cases harbored MYC rearrangement (R). The frequency of MYC‐R was much higher in GCB than in non‐GCB tumors (40/165, 24% vs 5/85, 6%) (P =.0001). MYC/BCL2 DE was observed in 53 of 125 (42%) cases. COO classification failed to predict overall survival (OS) in DLBCL patients, either those patients with MYC‐R were included (P =.10) or not (P =.27). In contrast, MYC‐R and MYC/BCL2 DE significantly correlated with inferior OS (P =.0001 and P =.001, respectively). In multivariate analysis, MYC‐R and MYC/BCL2 DE were still independent prognostic factors in DLBCL patients. Conclusions: MYC‐R and MYC/BCL2 DE are independent prognostic factors for DLBCL patients treated with R‐CHOP. In this cohort, COO classification failed to stratify patient outcome. [ABSTRACT FROM AUTHOR]

Objective. To observe the expression of monocyte chemotactic protein 1 (MCP-1) in acute lung injury (ALI) rat model, to characterize its effect on the development and progression of ALI, and to identify the potential new drug delivery approach during in vivo experiment. Method. The effects of different doses of lipopolysaccharide (LPS) on human pulmonary artery endothelial cells (HPAEC) were tested. For the animal experiments, thirty Sprague-Dawley (SD) rats were divided into physiological saline control group (NC group), the LPS model group (L group), the antagonist RS102895 combined with LPS group (R + L group), and the antagonist RS102895-loaded polyaldehyde dextran nanoparticles combined with LPS group (DNPR + L group). The blood gas analysis and dry/wet weight ratio were detected 24 hours after interventions. The levels of inflammatory factors, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were tested by ELISA. The expression of monocyte chemoattractant protein-1 (MCP-1) in lung tissues was examined through Western blot, and the change of MCP-1 mRNA expression level was detected by performing RT-PCR. Result. LPS was responsible for inducing ALI in rats, and the degree of cell damage was dose-dependent. Blood gas analysis of L group showed that PaO2 and PaO2/FiO2 levels were significantly lower than those of the NC group (P<0.05), while the dry/wet weight ratio of lung tissues in L group increased (P<0.05). Inflammatory factors including TNF-α and IL-1β and the expression of MCP-1 in both protein and mRNA levels were higher in L group than in the NC group (P<0.05). The inhibition of the interaction between MCP-1 and chemokines receptor 2 (CCR2) by antagonist RS102895 can significantly alleviate the ALI in rats, which is accompanied by a significant decrease of inflammatory factors and MCP-1 expression (P<0.05). Compared with R + L group, treatment with DNPR and LPS combination significantly improved the condition of rats and decreased the level of TNF-α, IL-1β, and MCP-1 expression (P<0.05). Conclusion. In ALI, RS102895 can inhibit the MCP-1/CCR2 interaction, therefore, retarding the progress of ALI. Because of the high transfection efficiency of inhibitor RS102895packgaed by polyaldehyde dextran nanoparticles, this phenomenon particularly reached a significant level. The results imply new insights for the treatment of ALI. [ABSTRACT FROM AUTHOR]