KDM6B, also known as JMJD3, is a member of the family of histone lysine demethylase (KDMs), which is closely related to many types of cancers. However, its role and the underlying mechanisms in ovarian cancer remain unknown. Here we show that KDM6B is elevated in epithelial ovarian cancer and its expression level is closely related with metastasis and invasion. In addition, survival analysis showed that high expression of KDM6B was associated with low overall survival in ovarian cancer patients. Overexpression of KDM6B in epithelial ovarian cancer cells promoted proliferation, epithelial‐mesenchymal transition (EMT), migration and invasion in vitro, and enhanced metastatic capacities in vivo. On the contrary, silencing KDM6B in invasive and metastatic ovarian cancer cells inhibited these processes. Mechanistically, we found that KDM6B exerts its function by modulating the transforming growth factor‐β1 (TGF‐β1) expression, and TGF‐β1 signal pathway inhibitor LY2157299 significantly inhibited KDM6B‐induced proliferation, migration, metastasis, and EMT in ovarian cancer cells. Our findings, for the first time, reveal the pivotal role of KDM6B in the invasion and metastatic behavior of epithelial ovarian cancer. Thus, targeting KDM6B may be a useful strategy to interfere with these behaviors of epithelial ovarian cancer.
Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma that is unique and different from systemic diffuse large B-cell lymphomas. The median age at diagnosis of PCNSL is 65 years and its incidence is rising rapidly in the elderly population. A total of ≥20% of all patients with PCNSL are ≥80 years old. Notably, age has been identified as an independent poor prognostic factor for PCNSL. Elderly patients have an inferior prognosis to that of younger patients and are more severely affected by iatrogenic toxicity; therefore, elderly patients represent a unique and vulnerable treatment subgroup. The present review summarized the available literature to provide an improved understanding of the epidemiology, clinical characteristics, diagnosis, prognosis and management of PCNSL in the elderly population. Notably, the incidence of PCNSL in immunocompetent elderly patients, predominantly in men, is increasing. For the diagnosis of CNSL, imaging-guided stereotactic biopsy is considered the gold standard. When stereotactic biopsy is not possible or conclusive, certain biomarkers have been described that can help establish a diagnosis. PCNSL has a very poor prognosis in the elderly, even though several prognostic scoring systems exist and several prognostic markers have been reported in patients with PCNSL. Furthermore, the treatment of elderly patients remains challenging; it is unlikely that a novel agent could be used as a curative monotherapy; however, a combination of novel agents with polychemotherapy or its combination with other novel drugs may have therapeutic potential. Contents1. Epidemiology 2. Clinical manifestation 3. Brain imaging
At a follow-up of 34 months, the patient remains in remission without further treatment, suggesting low-dose rituximab seems to be a safe and effective regimen for the elderly patients with acquired haemophilia.
Interleukin (IL)-37 has an important role in autoimmune diseases by suppressing immunity and inflammation; however, the role of IL-37 in immune thrombocytopenia (ITP) has remained largely elusive. The present study aimed to investigate the expression of IL-37 and its potential role in the pathogenesis of ITP. The plasma levels and expression of IL-37 in the peripheral blood mononuclear cells of patients with active ITP, ITP patients in remission and healthy controls were measured by ELISA and reverse transcription-quantitative PCR, respectively. The levels of IL-37 in patients with ITP treated with and without glucocorticoids were also determined by ELISA. Specific anti-platelet glycoprotein (GP)IIb/IIIa and/or GPIb/IX autoantibodies were assayed by modified monoclonal antibody-specific immobilization of platelet antigens. The mean value of plasma IL-37 in ITP patients was slightly higher than that in healthy controls, but this was not statistically significant. There was no correlation between IL-37 and anti-platelet autoantibodies, and no significant difference in the IL-37 concentration was identified between patients treated with and without glucocorticoids. In addition, the correlation between IL-37 and the platelet count was analyzed, with no statistical significance observed. It was therefore concluded that IL-37 may not have a pivotal role in the development of ITP. However, the lack of significant differences may be due to the limited number of patients in different groups. A larger number of ITP patients should be enrolled in the future work and achieve more accurate results.
BackgroundBortezomib is recently studied as a novel agent in indolent lymphoma. The optimal schedule of bortezomib used in indolent lymphoma is still uncertain.MethodsWe did a systematic review and meta-analysis of the clinical trials comparing the efficacy and toxicity of the weekly and biweekly schedules of bortezomib in patients with indolent lymphoma. We searched Pubmed, Cochrane Library and Emabase from inception to July 29, 2016. The primary outcome was the overall response rate including the complete response rate and the partial response rate. The secondary outcomes were the proportions of patients in each group experiencing the adverse events including the neutropathy, fatigue, diarrhea, nausea and neutropenia.FindingsAfter final screening, six trials were considered eligible for analysis. The results showed that the overall response rate of biweekly schedule was higher than that of weekly schedule in indolent lymphoma (OR 1.691;95%CI 1.02–2.80). Furthermore, there were no significant differences between the two schedules of bortezomib for the main adverse events.InterpretationThe biweekly schedule of bortezomib was more effective than the weekly schedule in indolent lymphoma, with similar proportion of toxicities.
To investigate the expression of tumour necrosis factor superfamily 13B (TNFSF13B) receptors in immune thrombocytopenia (ITP) and their correlation with disease activity, we investigated the protein and mRNA levels of TNFSF13B, tumour necrosis factor receptor superfamily 13C (TNFRSF13C), TNFRSF13B and TNFRSF17 by flow cytometry, enzyme-linked immunosorbent assay and real time quantitative polymerase chain reaction. All CD19(+) B lymphocytes expressed TNFRSF13C by flow cytometry, but the mean fluorescence intensity (MFI) was decreased in patients with active disease compared to patients in remission and healthy controls, while no significant difference of TNFRSF13C mRNA was found between ITP patients and controls. The mRNA and plasma TNFSF13B were elevated in active ITP patients, and TNFRSF13C MFI level was inversely correlated with plasma TNFSF13B in active patients. In vitro assays showed that TNFRSF13C MFI was decreased after long exposure to TNFSF13B. No significant difference for TNFRSF13B or TNFRSF17 was found between ITP patients and controls. In conclusion, TNFRSF13C expression is reduced on CD19(+) cells in active ITP patients. This down-regulation occurs through a post-transcriptional mechanism and could be a consequence of chronic increase of TNFSF13B.
Background: Several clinical trials have been conducted to evaluate the role of maintenance therapy in untreated diffuse large B-cell lymphoma (DLBCL) patients with complete response or partial response following standard immunochemotherapy; however, the effect of maintenance therapy remains uncertain, and a suitable maintenance strategy has not been determined because of the lack of direct/indirect comparisons. Methods: We performed a systematic review and Bayesian network meta-analysis (NMA) to analyze and compare the effectiveness of different maintenance regimens in newly diagnosed DLBCL patients. We searched the PubMed Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials for relevant papers from inception to 18 March 2021. Our study was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42020168864). Data on overall survival (OS) were extracted and the treatments were ranked using the surface under the cumulative ranking (SUCRA) curve. Results: Eight trials and seven treatments involving 3525 patients were analyzed. OS analysis indicated that none of the drugs showed any benefit compared with non-maintenance therapy. Maintenance therapy with lenalidomide (SUCRA 69.3%) was ranked first in terms of OS. Conclusion: Based on the OS results observed in this NMA, we do not recommend maintenance therapy in patients with newly diagnosed DLBLC after first-line therapy.
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