ABSTRACT
Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.
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Objective To preliminarily study the role of activated platelets in inflammatory response in ischemic stroke by using the platelet and vascular endothelial cell co-culture model.Methods Platelets were isolated from healthy donator's peripheral blood and activated in vitro by 0.8 μmol/L ADP in ischemic stroke; resting platelets were also chosen.The mean platelet component (MPC)concentration was measured by hematology analyzer.Resting platelets and activated platelets were co-cultured with vascular endothelial cells for 12 h,respectively; the other 2 control groups (ADP only,blank) were employed in the experiment.RT-PCR was used to detect the expression level of mRNA of proinflammatory cytokines in the endothelial cells,including IL-1β,IL-6,IL-8 and MCP-1.Results Compared with the resting platelets[(266.80±22.14) g/L],ADP-induced activated platelets[(231.90±14.63) g/L]showed significantly lower concentration of MPC (P<0.05).Activated platelets in the co-culture model could induce the mRNA expression of IL-1β,IL-6,IL-8 and MCP-1 in the endothelial cells,while resting platelets could not.Conclusion Activated platelets can trigger an interaction between platelets and endothelial cells in vitro,and induce the mRNA expression of proinflammatory cytokines in the endothelial cells,which may be one of the mechanisms of inflammatory response in iscbemic stroke.
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AIM:To observe the effect of immune-activated platelets and low-density lipoprotein cholesterol (LDL) on the expression and activity of cyclooxygenase-2 (COX-2) and peroxisome proliferator activated receptor ? (PPAR-?) in human umbilical vein endothelial cells (HUVECs) treated with activated platelets and LDL.METHODS:The platelets were activated by ADP.The co-culture system of HUVECs with immune activated platelets and/or LDL were established.The activity of COX-2 and expression of PPAR-? at mRNA and protein levels in HUVECs were detected by RT-PCR and Western blotting.The concentration of PGE2 was measured by ELISA for representing the COX-2 activity.The PPAR-? activity was determined by a nuclear factor assay kit.RESULTS:The COX-2 activity and mRNA expression of PPAR-?,the protein levels of COX-2 and PPAR-? and PGE2 concentration in activated platelets group were significant higher than those in un-activated platelets group (all P
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Objective To investigate the leukocyte infiltration inside the hematoma and the correlation between this and the expression of platelet P-selectin (CD62p) and platelet thrombin-sensitive protein (TSP) of patients with cerebral hemorrhage. Methods In 33 patients with cerebral hemorrhage treated with minimally invasive surgery, the expressions of platelet CD62p and TSP were detected by flow cytometry (FCM) and leukocyte counts were measured in intracerebral hematoma fluid and venous blood. The correlation analysis was performed between the two variables.Results The expressions of platelet CD62p and TSP in hematoma fluid were higher in patients with acute cerebral hemorrhage (20.25?1.82, 37.04?3.63) than those in venous blood (7.72?2.19, 12.32?2.81)(all P
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Objective To investigate the levels and its clinical significance of activated platelets in patients with transient ischemic attack(TIA). Methods Color Doppler flow imaging was used to measure the degree of carotid atherosclerosis in 72 patients with TIA(TIA group). Flow cytometry (FCM) was used to measure the levels of PAC-1 and CD62P. They were compared with 30 healthy controls(NC guoup). Results The levels of PAC-1 and CD62P in TIA group were significantly higher than those in NC group (allP