The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC) inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA) as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL). This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256), the overall response rate (ORR) and disease control rate (DCR) were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127). For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS) was 129 (95% CI 82 to 194) days for the monotherapy group and 152 (95% CI 93 to 201) days for the combined therapy group (P = 0.3266). Most adverse events (AEs) were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2%) and neutropenia (6.2%). For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%), neutropenia (12.6%), anemia (7.1%), and fatigue (5.5%). This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0439-6) contains supplementary material, which is available to authorized users.
Background: Ribonucleotide reductase M2 (RRM2) is a rate-limiting step for DNA synthesis. It is still unknown how RRM2 is involved in decidualization. Results: RRM2 is highly expressed in the decidua and up-regulated by progesterone and DNA damage. Decidualization is significantly inhibited by specific RRM2 inhibitors. Conclusion: RRM2 is essential for mouse decidualization. Significance: This study will shed light on understanding the mechanism underlying decidualization.
Background
Human bone marrow-derived mesenchymal stem cells (HBMSCs) are characterized by multiple differentiation potential and potent self-renewal ability, yet much remains to be elucidated on what determines these properties. Long-chain noncoding RNAs (lncRNAs) have been suggested to be involved in multiple biological processes under physiological and pathological conditions, including osteogenic differentiation.
Methods
Alkaline phosphatase (ALP) activity assay, ALP staining, and Alizarin Red Staining were used for osteogenic potential detection. Western blot and qRT-PCR were used to examine the expression of LINC00707 and miR-370-3p. RNA-binding protein immunoprecipitation was used to detect the interaction between LINC00707 and RNA-induced silencing complex. Luciferase reporter assay was used to confirm the binding sites of miR-370-3p to LINC00707 and WNT2B.
Results
We demonstrated that LINC00707 expression was gradually increased in HBMSCs during consecutive osteogenic induction, and it could further positively regulate the osteogenic differentiation both in vitro and in vivo, whereas LINC00707 inhibition led to suppressed osteogenic differentiation. Thereafter, we inferred a predicted interaction between LINC00707 and miR-370-3p and then confirmed the direct binding sites of miR-370-3p on LINC00707. While miR-370-3p upregulation led to decreased osteogenic differentiation, LINC00707 overexpression could reverse this suppression, indicating that LINC00707 acts as a competing endogenous RNA (ceRNA) for miR-370-3p. Moreover, LINC00707 could act as a ceRNA to upregulate WNT2B via miR-370-3p inhibition.
Conclusions
In conclusion, our study provides a novel lncRNA-miRNA regulatory network and a promising target to modulate the osteogenic differentiation of HBMSCs.
Electronic supplementary material
The online version of this article (10.1186/s13287-019-1161-9) contains supplementary material, which is available to authorized users.
BackgroundDelayed implantation is a developmental arrest at the blastocyst stage and a good model for embryo implantation. MicroRNAs (miRNAs) have been shown to be involved in mouse embryo implantation through regulating uterine gene expression. This study was to have an integrative analysis on global miRNA and mRNA expression in mouse uterus under delayed implantation and activation through Illumina sequencing.Methodology/Principal FindingsBy deep sequencing and analysis, we found that there are 20 miRNAs up-regulated and 42 miRNAs down-regulated at least 1.2 folds, and 268 genes up-regulated and 295 genes down-regulated at least 2 folds under activation compared to delayed implantation, respectively. Many different forms of editing in mature miRNAs are detected. The percentage of editing at positions 4 and 5 of mature miRNAs is significantly higher under delayed implantation than under activation. Although the number of miR-21 reference sequence under activation is slightly lower than that under delayed implantation, the total level of miR-21 under activation is higher than that under delayed implantation. Six novel miRNAs are predicted and confirmed. The target genes of significantly up-regulated miRNAs under activation are significantly enriched.ConclusionsmiRNA and mRNA expression patterns are closely related. The target genes of up-regulated miRNAs are significantly enriched. A high level of editing at positions 4 and 5 of mature miRNAs is detected under delayed implantation than under activation. Our data should be valuable for future study on delayed implantation.
Periodontal ligament stem cells (PDLSCs) are characterized by multiple differentiation potential and potent self‐renewal ability, yet much remains to be elucidated that what determines these properties. Long noncoding RNAs (lncRNAs) have been suggested to involve in multiple biological process under physiological and pathological conditions, including osteogenic differentiation. In the present study, we performed comprehensive lncRNA profiling by lncRNA microarray analysis and identified prostate cancer‐associated ncRNA transcript‐1 (lncPCAT1) was gradually increased in PDLSCs during consecutive osteogenic induction, and it could further positively regulate the osteogenic differentiation both in vitro and in vivo, whereas lncPCAT1 inhibition led to suppressed osteogenic differentiation. Thereafter, we inferred a predicted interaction between lncPCAT1 and miR‐106a‐5p and then confirmed the direct binding sites of miR‐106a‐5p on lncPCAT1. Although miR‐106a‐5p upregulation led to decreased osteogenic differentiation, lncPCAT1 overexpression could reverse its suppression, indicating that lncPCAT1 act as a competing endogenous RNA for miR‐106a‐5p. Moreover, lncPCAT1 could sponge miR‐106a‐5p to upregulate miR‐106a‐5p‐targeted gene BMP2, which was a crucial gene involved in osteogenic differentiation. Interestingly, we found that E2F5, another target of miR‐106a‐5p, could bind to the promoter of lncPCAT1 and then form a feed‐forward regulatory network targeting BMP2. In conclusion, our study provided a novel lncRNA‐miRNA feed‐forward regulatory network and a promising target to modulate the osteogenic differentiation of PDLSCs.
An accurate estimation of prognosis of the esophageal carcinoma patients after surgery is urgently needed. Clinical nomogram has been developed to quantify risk by incorporating prognostic factors for individual patient. Based on the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2013, a total of 4566 patients were selected. Of those, 3198 patients were assigned to training set to construct the nomogram, which incorporated age, gender, histology, grade, T stage, N stage, nodes examined, radiation and chemotherapy. The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. The C-index of the nomogram was 0.71(95%CI 0.70-0.72), which was statistically higher than the TNM staging system. The results were then validated using bootstrap resampling and a validation set of 1368 patients in the SEER database. Besides, in the esophageal squamous cell carcinoma and esophageal adenocarcinoma subgroups, the nomogram discrimination was superior to the TNM staging system. It is likely that these results would play a supplementary role in the current staging system and help to identify the high risk population after surgery.
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