High MNK1 expression in EOC tissues indicates poor clinical outcomes, and MNK1 can act as a potential target for novel chemotherapy development towards EOC.

No abstract

To explore the expression changes of potential key genes and relevant biological processes in peripheral blood mononuclear cells of children with newly diagnosis of type 1 diabetes (T1D).Microarray data GSE9006 were downloaded from Gene Expression Omnibus (GEO) database, including peripheral blood mononuclear cells samples from 43 children with newly diagnosed T1D (NEW), 19 one-month (1-MO) follow-up samples, 19 4-month (4-MO) follow-up samples and 24 healthy controls. The differentially expressed genes (DEGs) were identified using Affy package in R, and cluster analysis of DEGs were performed following functional enrichment analysis with Database for Annotation, Visualization and Integrated Discovery (DAVID) and construction of protein-protein interaction (PPI) network with STRING database.We identified 73, 73, 96 DEGs in NEW group, 1-MO group and 4-MO group, respectively by comparing with healthy controls with |logFC|>0.58 and P-value<0.05. The cluster analysis of these DEGs showed that 4 genes, including human leukocyte antigen (HLA-DQA1), HLA-DRB4, integrin 3 (ITGB3) and killer cell lectin-like receptor subfamily F member 1 (KLRF1) were all significantly expressed in 3 groups, which were significantly enriched in asthma, T1D and intestinal immune network for IgA production pathway. And 57 genes enriched in cluster 5, which were only differentially expressed in NEW group, were involved in response to wounding, inflammatory response and blood coagulation as well as chemokine signaling pathway. Besides, the hub genes in PPI network of cluster 5 were identified, containing FOS, pro-platelet basic protein (PPBP), interleukin 8 (IL8), formyl peptide receptor-like 2 (FPR2) and platelet factor 4 (PF4).HLA-DQA1, HLA-DRB4, ITGB3 and KLRF1 might be targets for treatment of T1D, and 5 hub proteins, FOS, PPBP, IL8, FPR2 and PF4, were likely to be new markers for diagnosis of T1D.

Background:Rituximab is an effective therapy for rheumatoid arthritis (RA) patients with inadequate responses to methotrexate (MTX)1, 2. However, it has not been registered or approved in China for the treatment of RA by far. HLX01, an approved rituximab biosimilar (demonstrated in Chinese patients with diffuse large B-cell lymphoma)3, is thus evaluated in this study for the benefits of Chinese RA patients.Objectives:This study aimed to evaluate the efficacy and safety of HLX01 plus MTX versus placebo plus MTX in Chinese patients with active RA who had inadequate responses to MTX.Methods:This was a randomised, double-blind, placebo-controlled phase 3 study conducted in China (NCT03522415). Eligible patients were randomised 2:1 to receive intravenous infusion of 2×1000 mg HLX01 or placebo on day 1 and day 15. Patients with inadequate responses at week 16 and 20 were allowed to receive rescue treatments. Patients were retreated with or switched to receive (if initially assigned to placebo) 2×1000 mg rituximab at the first day of week 24 and 26. The primary endpoint of this study was the American College of Rheumatology criteria (ACR) 20 response at week 24. Secondary efficacy endpoints were evaluated at week 12, 24, 36 and 48. The safety, pharmacokinetics, pharmacodynamics and immunogenicity of HLX01 were observed and analyzed throughout the study.Results:Between May 28, 2018 and Sep 11, 2020, a total of 275 patients (ITT set) were randomised and 263 patients without major protocol deviations were included in per-protocol set (PPS). At week 24, HLX01 showed statistically superior efficacy (p <0.001) to placebo (ACR20: 60.7% vs 35.9% in ITT set, 60.3% vs 37.1% in PPS). Secondary efficacy endpoints were also significantly improved in HLX01 group compared with placebo (Table 1). The overall incidence of serious treatment emergent adverse events (TEAEs), adverse drug reactions (ADRs), and TEAEs leading to drug discontinuation were similar among treatment groups, with the most common TEAE been upper respiratory tract infection before (18.1% vs 18.5%) or after (13.0% vs 12.3%) week 24. Serum concentrations, immunogenicity and pharmacodynamics were similar between HLX01 and placebo groups.Table 1.Results of secondary efficacy endpoints at week 12, 24, 36 and 48 in ITT set.DurationSecondary efficacy endpointsACR20 (%)ACR50 (%)ACR70 (%)DAS28-CRP(mean)HAQ-DI(mean)HLX01PlaceboHLX01PlaceboHLX01PlaceboHLX01PlaceboHLX01PlaceboBaseline5.495.431.401.45Week 1248.132.621.910.94.45.43.894.471.021.22Week 2460.735.936.618.515.312.03.394.370.871.22Week 3660.148.946.431.532.217.42.883.510.710.97Week 4873.862.055.240.239.927.22.823.510.721.03Conclusion:Comparing with placebo plus MTX, HLX01 plus MTX showed significantly improved clinical outcomes and comparable safety profiles in Chinese patients with moderately to severely active RA who had inadequate responses to MTX, demonstrating HLX01 in combination with MTX as a well-tolerated, safe and efficient treatment option.References:[1]Emery P, Deodhar A, Rigby WF, et al. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis. Sep 2010;69(9):1629-35. doi:10.1136/ard.2009.119933.[2]Rubbert-Roth A, Tak PP, Zerbini C, et al. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR). Rheumatology (Oxford). Sep 2010;49(9):1683-93. doi:10.1093/rheumatology/keq116.[3]Shi Y, Song Y, Qin Y, et al. A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. J Hematol Oncol. Apr 16 2020;13(1):38. doi:10.1186/s13045-020-00871-9.Acknowledgements:The authors would like to thank participants in this study and their families. They would also like to acknowledge other investigators and staff at all clinical sites and the members of the Independent Data Monitoring Committee.Disclosure of Interests:None declared