Objective Serum miRNA has been regarded as a potential biomarker for diagnosis, therapeutic evaluation and prognostic prediction in cancer patients. This study aims to explore the clinical significance of the expression level of metastasis- related microRNA (miR- 18b) in the serum in AFP- negative (≤ 20 ng/ml) hepatocellular carcinoma(HCC) patients receiving radiofrequency ablation (RFA). Methods A total of 131 HCC patients with negative serum AFP, who were encountered during the period from January 2007 to January 2011 at authors’ hospital, were enrolled in this study. Radiofrequency ablation (RFA) of the lesions was carried out in all patients. Serum samples were collected before RFA. Forty - three healthy individuals were selected for control. The expression level of serum miR - 18b was deternmined by using quantitative real- time PCR method in all the patients and the healthy individuals. The correlations of the expression level of serum miR - 18b with clinico - pathological factors, postoperative recurrence, overall cirrhosis (P = 0.035), tumor diameter (P < 0.01) and tumor differentiation (P = 0.020). During the follow-up period, 79 patients (60.3%) developed recurrent tumors, and the expression level of serum miR- 18b in them was dramatically higher than that in the patients showing no recurrence (3.26 ± 1.28 vs. 2.42 ± 0.86, P <0.01). The incidence of recurrence after RFA, especially distant intrahepatic metastasis, in patients with higher expression level of serum miR- 18b was strikingly higher than that in patients with lower expression level of serum miR- 18b (72.3% vs. 48.5%, P = 0.005). Kaplan- Meier survival analysis indicated that both overall survival rate and recurrence- free survival rate of patients with higher expression level of serum miR-18b were significantly lower than those of patients with lower expression level of serum miR- 18b. Conclusion The expression level of serum miR - 18b is significantly elevated in AFP - negative HCC patients. The expression level of serum miR- 18b might be used as an ideal biomarker for monitoring tumor recurrence as well as for predicting prognosis after RFA.

Tumor microenvironment has been widely utilized for advanced drug delivery in recent years, among which hypoxia-responsive drug delivery systems have become the research hotspot. Although hypoxia-responsive micelles or polymersomes have been successfully developed, a type of hypoxia-degradable nanogel has rarely been reported and the advantages of hypoxia-degradable nanogel over other kinds of degradable nanogels in tumor drug delivery remain unclear. Herein, we reported the synthesis of a novel hypoxia-responsive crosslinker and the fabrication of a hypoxia-degradable zwitterionic poly(phosphorylcholine)-based (

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.