ABSTRACT
Malignant tumor is one of the important reasons threatening human health and safety at present. The application of antiangiogenic drugs and immune checkpoint inhibitors has brought great hope for tumor treatment, but the complex interlaced relationship between tumor blood vessels and immune microenvironment leads to unsatisfactory efficacy. In addition,VEGF, a key driver of tumor angiogenesis, interferes with the maturation of dendritic cells, thereby inhibiting the initiation of T cells. VEGF also induces depletion of CD8+T cells. At the same time, various innate and acquired immune cells secrete angiogenic factors that accelerate uncontrolled angiogenesis and promote vascular immaturity. Therefore targeting tumor blood vessels and immunity is a potential strategy for enhancing tumor immunotherapy. In recent years numerous studies have found that using the blood vessels and the immune intervention strategies combined with antitumor immune therapy has achieved good results. In this review the immune and vascularized tumor microenvironment are reviewed and discussed, and the research progress of vascularized immune interintervention strategy for tumor treatment in recent years is reviewed so as to provide reference for further improving the efficacy of tumor immunotherapy.
ABSTRACT
This study screened excellent carriers for co-loading tanshinone Ⅱ_A(TSA) and astragaloside Ⅳ(As) to construct antitumor nano-drug delivery systems for TSA and As. TSA-As microemulsions(TSA-As-MEs) were prepared by water titration. TSA-As metal-organic framework(MOF) nano-delivery system was prepared by loading TSA and As in MOF by the hydrothermal method. Dynamic light scattering(DLS), transmission electron microscopy(TEM), and scanning electron microscopy(SEM) were used to characterize the physicochemical properties of the two preparations. Drug loading was determined by HPLC and the effects of the two preparations on the proliferation of vascular endothelial cells, T lymphocytes, and hepatocellular carcinoma cells were detected by the CCK-8 method. The results showed that the particle size, Zeta potential, and drug loading of TSA-As-MEs were(47.69±0.71) nm,(-14.70±0.49) mV, and(0.22±0.01)%, while those of TSA-As-MOF were(258.3±25.2) nm,(-42.30 ± 1.27) mV, and 15.35%±0.01%. TSA-As-MOF was superior to TSA-As-MEs in drug loading, which could inhibit the proliferation of bEnd.3 cells at a lower concentration and improve the proliferation ability of CTLL-2 cells significantly. Therefore, MOF was preferred as an excellent carrier for TSA and As co-loading.
Subject(s)
Mice , Animals , Endothelial Cells , Abietanes , Cell LineABSTRACT
Objective @#To identify spatio-temporal distribution patterns of mumps in Zhejiang Province from 2008 to 2019, so as to provide insights into precise control of mumps.@*Methods @#The epidemiological data pertaining to mumps in Zhejiang Province from 2008 to 2019 were collected from the China Information System for Disease Control and Prevention. The time- and region-specific incidence of mumps was descriptively analyzed, and the spatio-temporal clustering characteristics of mumps incidence were identified using global and local spatial autocorrelation analyses and spatio-temporal scan analysis.@*Results @#A total of 167 196 cases of mumps were reported in Zhejiang Province from 2008 to 2019, and the incidence of mumps reduced from 56.08/105 in 2008 to 11.35/105 in 2019, with a reduction of 79.76%. There was no remarkable mumps seasonality since 2017; however, spatial autocorrelation was seen in mumps incidence in 2008, 2011 and 2012, respectively ( Moran's I coefficient=0.16, 0.18, 0.16; all P<0.05 ). Spatio-temporal scan analysis identified five spatio-temporal clusters of mumps incidence in 2008, 2011 and 2012, and the most likely spatio-temporal cluster was mainly concentrated in Cangnan County of Wenzhou City, covering 17 counties clustered in the time frame from 15 January 2008 to 28 February 2009, while the other four clusters were concentrated in Pinghu City of Jiaxing City, Kaihua County of Quzhou City, Fuyang District of Hangzhou City and Zhuji City of Shaoxing City, clustered in the time frame from 15 January 2008 to 30 June 2012. @*Conclusion @#The incidence of mumps appeared a tendency towards a reduction in Zhejiang Province from 2008 to 2019, and rebounded in some regions. No remarkable mumps seasonality was seen since 2017. The spatio-temporal clusters of mumps incidence were concentrated in Wenzhou and Jiaxing cities of Zhejiang Province in 2008, 2011 and 2012; however, no spatial cluster was identified since 2012.