A novel inhibitor of MDM2 oncogene blocks metastasis of hepatocellular carcinoma and overcomes chemoresistance

Overexpression of the MDM2 oncogene and mutations in the p53 tumor suppressor commonly occur in hepatocellular carcinoma(HCC)and are associated with increased mortality due to this disease.Inhibiting MDM2 has been demonstrated to be a valid approach for the treatment of HCC.However,most of the MDM2 inhibitors evaluated to date have been designed to block the MDM2 and p53 binding,and have limited efficacy against tumors with mutant or deficient p53.In the present study,we developed a novel MDM2 inhibitor(termed SP141)that has direct effects on MDM2 and exerts anti-HCC activity independent of the p53 status of the cancer cells.We demonstrate that SP141 inhibits cell growth and prevents cell migration and invasion,independent of p53.Mechanistically,SP141 directly binds the MDM2 protein and promotes MDM2 degradation.The inhibition of MDM2 by SP141 also increases the sensitivity of HCC cells to sorafenib.In addition,in orthotopic and patient-derived xenograft models,SP141 inhibits MDM2 expression and suppresses tumor growth and metastasis,without any host toxicity.Furthermore,the inhibition of MDM2 by SP141 is essential for its anti-HCC activities.These results provide support for the further development of SP141 as a lead candidate for the treatment of HCC.

Recent progress in ultraviolet and deep-ultraviolet nonlinear optical aluminoborates

Aluminoborates(ABOs)show wide ultraviolet(UV)transmittance,and are one of the important types of UV and deep-UV nonlinear optical(NLO)materials.In recent years,the combination of AlO_(n)(n=4,5,6)polyhedra or their fluorinated analogues with different polyborate anions leads to a rich variety of crystalline ABOs.In this review,we summarize the recent developments of UV and deep-UV NLO inorganic ABOs.These ABOs can be grouped into three types in terms of their compositions:(i)aluminum oxyborates,(ii)alkali/alkaline earth metal aluminoborates,and(iii)alkali/alkaline earth metal aluminoborate fluorides and fluoroaluminoborates.We discuss the synthesis,structural features,NLO properties,as well as related structure-performance relationships of these non-centrosymmetric ABOs.Finally,the future perspectives in this field are discussed.

Detection of circulating tumor cells in hepatocellular carcinoma: applications in diagnosis, prognosis prediction and personalized treatment

Hepatocellular carcinoma(HCC)is one of the most common malignant tumors worldwide and is associated with poor clinical prognosis,which is mainly caused by tumor recurrence and metastasis.Circulating tumor cells(CTCs)are tumor cells shed into the bloodstream and regarded as the“seeds”of tumor recurrent or metastatic lesions.Over the past decade,the clinical value of CTC analysis has been extensively explored.CTC analysis is a representative form of liquid biopsy,offering a novel solution that can bypass the problems of invasive biopsy procedures,enabling comprehensive,non-invasive,and real-time disease monitoring.In HCC,CTC analysis has facilitated early detection and prognosis prediction,as well as treatment monitoring and therapeutic intervention guiding.In this review,we summarize available literature and provide an overview of CTC biology,detection technologies,and clinical applications in the diagnosis,prognosis prediction,and personalized treatment of HCC.