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Objective:To investigate the tumor perfusion enhancement induced by low intensity ultrasound stimulated microbubble cavitation (USMC) combined with programmed cell death-Ligand 1(PD-L1) antibody on improving the immune microenvironment of solid tumors.Methods:Tumor-bearing mice were divided into 4 groups: Control ( n=26) group, USMC ( n=27) group, anti-PD-L1 ( n=27) group and USMC+ anti-PD-L1 ( n=27) group. USMC treatment was performed with a VINNO 70 ultrasound theranostics system. Tumor perfusion was evaluated by contrast-enhanced ultrasound (CEUS). The anti-tumor efficacy was assessed by the tumor growth curve and the survival time of mice. The number and function of CD8 + T cells, the differentiation of CD4 + T cells, the proportion of MDSC and the phenotype distribution of TAM in tumors were analyzed by flow cytometry. The content of CXCL9, CXCL10 and HIF-1α in tumor were detected by ELISA. The expression of VEGF in tumor tissues was analyzed by immunofluorescence. Results:CEUS showed that the values of PI and AUC of tumors were significantly increased after USMC compared with before USMC (all P<0.05). USMC combined with anti-PD-L1 therapy did suppress the tumor progression. FCM showed the number, the expression of proliferation antigen Ki67, the secretion of IFN-γ and Granzyme B of CD8 + T cells in tumors were higher in combined group than those in other three groups after therapy (all P<0.05). Meantime, the proportion of Th1 was rose while Tregs and MDSC were declined and the polarization of TAM was toward M1 type by combined therapy. ELISA analysis showed that the combined therapy also increased the concentration of CXCL9, CXCL10 and decreased the content of HIF-1α in tumors (all P<0.05). Meanwhile, the immunofluorescence expression of VEGF was significantly lower in combined group than that in the control group after treatment ( P<0.05). Conclusions:Tumor perfusion enhancement by USMC combined with PD-L1 antibody therapy could improve tumor immune microenvironment and USMC might be a novel effective method for potentiating PD-L1 antibody immunotherapy.
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Objective To investigate the effect of CT total tumor perfusion parameters in the identification of benign and malignant lung lesions. Methods 80 patients with pulmonary space-occupying lesions who were treated in our hospital from December 2015 to May 2017 were enrolled. After pathological histological diagnosis, 52 cases of malignant lesions and 28 cases of benign lesions were confirmed. And they all underwent CT whole tumor perfusion scan and perfusion imaging analysis. And the blood flow, blood volume, average transit time and surface permeability were obtained.Some cases of histopathological specimens were treated by monoclonal CD34 staining method, and the microvascularrich areas in the specimens were selected for blood vessel counting. The morphology of blood vessels was observed and microvessel density was obtained. Results The levels of BF, BV, MTT and PS in benign lesions were significantly lower than those in patients with malignant lesions. The best diagnostic threshold, sensitivity and specificity of BF in lung occupying lesions was> 49.12 mL/100 mL, 80.00％ and 52.40％. The best diagnostic threshold, sensitivity and specificity of BV was 6.68 m L/100 mL, 70.00％ and 81.00％. The best diagnostic threshold, sensitivity and specificity of MTT was3.82 m L/100 mL, 97.50 ％ and 52.40％. The best diagnostic threshold, sensitivity and specificity of PS was 7.25 mL/100 mL, 92.50％ and 90.50％. The malignant lesion microvessel density count in the malignant lesions was significantly higher than that of benign lesions, and the difference was statistically significant (P<0.05). Conclusion CT total tumor perfusion parameters have a great auxiliary effect on the diagnosis of benign and malignant lung occupying lesions. Among them, PS and BV have the strongest sensitivity and are worthy of clinical promotion.
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OBJECTIVE: To determine the reliable perfusion parameters in dynamic contrast-enhanced MRI (DCE-MRI) for the monitoring antiangiogenic treatment in mice. MATERIALS AND METHODS: Mice, with U-118 MG tumor, were treated with either saline (n = 3) or antiangiogenic agent (sunitinib, n = 8). Before (day 0) and after (days 2, 8, 15, 25) treatment, DCE examinations using correlations of perfusion parameters (Kep, Kel, and AH from two compartment model; time to peak, initial slope and % enhancement from time-intensity curve analysis) were evaluated. RESULTS: Tumor growth rate was found to be 129% +/- 28 in control group, -33% +/- 11 in four mice with sunitinib-treatment (tumor regression) and 47% +/- 15 in four with sunitinib-treatment (growth retardation). Kep (r = 0.80) and initial slope (r = 0.84) showed strong positive correlation to the initial tumor volume (p < 0.05). In control mice, tumor regression group and growth retardation group animals, Kep (r : 0.75, 0.78, 0.81, 0.69) and initial slope (r : 0.79, 0.65, 0.67, 0.84) showed significant correlation with tumor volume (p < 0.01). In four mice with tumor re-growth, Kep and initial slope increased 20% or greater at earlier (n = 2) than or same periods (n = 2) to when the tumor started to re-grow with 20% or greater growth rate. CONCLUSION: Kep and initial slope may a reliable parameters for monitoring the response of antiangiogenic treatment.