Tumor blood vessels are characterized with insufficiency and distortion. Endothelial molecules of neovascularization and the heterogeneity of microvasculature in tumor interstitial are the basis for molecular-targeted ultrasonic evaluation of tumor angiogenesis, and has become focus in recent years. Research progresses of molecular-targeted ultrasonic imaging in angiogenesis and heterogeneity of tumors were reviewed in this article.

Objective To compare the differences in histological morphology and hemodynamics between benign and malignant tumor, as well as differences between the different perfusional regions in tumors of the same type. Methods Thirty cases with malignant breast carcinoma and 30 cases with fibroadenoma were inspected by contrast enhanced ultrasound with time-intensity quantitive analysis. Perfusion index like peak intensity(PI), area under the curve(AUC), time to peak(TTP) and wash-out time (WOT) were collected both inside and at the margin of focus. The ultrastructures of new microvessesl were observed routinely with microscopy and transmission electron microscopy. Results The curve of malignant tumor group was characterized as ascend rapidly and drop slowly while the benign group presented as ascend slowly and drop rapidly. The AUC and WOT of malignant tumor group were significantly higher than that of benign group,while the PI and TTP had no statistical difference. In malignant tumor group,PI, AUC and WOT of the margin of focus were significantly higher than that of inside region of focus,while TTP was the opposite. However,there was no statistical differences between the perfusion parameter inside and outside of focus in benign group. The ultrastructures of newly built blood vessels in malignant group had strong ability to split,which was different from normal endothelium cells but was similar to other tumor foci. The margin of foci were characterized with dilatating and distorting vessels,and the center of the foci were occupied by narrow,occlusive new vessels and contracted anamorphic endothelium cells and pericytes. Rich microvessel areas located in the margin of foci. Conclusions The perfusion pattern,modality of time-intensity curve, mean perfusion parameter and variance of regional perfusion parameters are valuable diagnostic basis in discriminating benign and malignant breast tumor. The density,modality,distribution,structure and function of new microvessels in tumor focus are also keystone factors when tumors are assessed by means of imaging.

Objective To investigate the angiogenesis characteristics of normal breast,simple hyperplasia,atypical hyperplasia,intraductal carcinoma in situ and invasive ductal carcinoma.Methods Twenty cases in normal controls,20 cases with simple hyperplasia,20 cases with atypical hyperplasia,20 cases with intraductal carcinoma in situ and 30 cases with invasive ductal carcinoma were inspected with power Doppler imaging(PDI)and contrast enhanced microvascular imaging(MVI)on the quantity,configuration and distribution of angiogenesis.The microvessel density(MVD)were detected by immunohistochemical technique.ResultsWith the progression of breast cancer,MVD and grades of PDI kept increasing.Meanwhile,the blood vessels became twisted and increased in quantity with expansion into the lesion,the configuration of blood vessels became disordered.However,the changes mentioned above were not obvious in the very early stages.they became significant from the atypical hyperplasia(AH)stage.Conclusions Contrast MVI and PDI may be useful to screen high risk population with high risk of breast cancer due to their detection of changes in angiogenesis of breast carcinoma and precancerous lesions.

Objective　To investigate the effects of anti-VEGF antibody on angiogenesis and on the proliferation and apoptosis of the osteosarcoma OS-732 cells and the vascular endothelial cells. Methods　The effects of polyclonal antibody against VEGF on OS-732 induced angiogenesis were observed by a stero-microscope and light microscope in a tumor model of the chick embryo chorioallantoic membrane (CAM). Furtheremore, the proliferation and apoptosis of tumor cells and vascular endothelial cells were examined by TdT-mediated dUTP nick and labelling (TUNEL) and immunohistochemical staining by using monoclonal antibody for proliferating cell nuclear antigen (PCNA). Results　The number of both the newly formed vessels in the tumor and the tumor population were significantly decreased in the anti-VEGF antibody group as compared with that of the PBS control group. The apoptotic index for tumor cell was higher in the anti-VEGF antibody treated group than that in the negative control group, but the proliferation index was not significantly different between them. At the same time, increased apoptotic cells and decreased proliferation in vascular endothelial cells were also noted. Conclusion　VEGF antibody can inhibit the neovascularization of OS-732, probabaly by the mechanism of inhibi-ting the proliferation and promoting the apoptosis of vascular endothelial cells, further, might be contributive to the apoptosis of tumor cells and result in suppression of tumor growth.

Objective To observe the effectiveness and safety of clopidogrel combined with fibrinolytic therapy for acute ST segment elevation myocardial infarction(STEMI).Methods From January 2004 to December 2006,a total of 158 STEMI patients in our hospital were treated with fibrinolytic agents combined with or without clopidogrel.There were 84 patients in clopidogrel group,including 66(78.6%)male,18(21.4%)female and 45(53.6%)elderly patients(aged ≥ 60 years);74 patients were in control group,including 58(78.4%)male,16 female(21.6%)and 40(54.1%)elderly patients.Clinical characteristics,patency of infarct-related artery(IRA),30 d major adverse cardiac events(MACE),recurrent angina and hemorrhage events of the two groups were retrospectively analyzed.Efficacy and safety of fibrinolytic therapy combined with clopidogrel in elderly patients(≥60 years old)subgroup were also estimated.Results Baseline clinical characteristics between the two groups were comparable.Clopidogrel therapy was associated with a higher proportion of patent IRA(69.1% vs 51.4%,P=0.035)and lower rates of cardiac death(0 vs 6.8%,P=0.047)and MACE(2.4% vs 12.2%,P=0.036).There was no significant difference in the incidence of recurrent angina(3.6% vs 2.7%,P=0.885),slight and severe hemorrhage events(7.1% vs 9.5%,P=0.811;1.2% vs 1.4%,P=0.533)between the two groups.In elderly patients,clopidogrel therapy was associated with a higher proportion of patent IRA(68.9% vs 45.0%,P=0.045),the declining tendency in MACE(2.2% vs 12.5%,P=0.155),but no significant differences in the other indexes.There were no significant differences in above-mentioned indexes between the elderly and younger patients in clopidogrel group.Conclusion Addition of clopidogrel to fibrinolytic therapy is safe and effective for both the elderly and younger STEMI patients.

Purpose:To study the characterics of angiogenesis induced by osteosarcoma OS-732 cell line. Methods:With a tumor model of the chick embryo chorioallantoic membrane(CAM),the angiogenesis induced by OS-732 cell line was observed by a stereo-microscope and transmission electron microscope, and the expression of angiogenic factors vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in xenografts of OS-732 cell line on CAM was detected by immunohistochemical technique. Results:This cell line was strongly angiogenic, which probably is associated with production of many factors.The new capillaries converging upon the tumor can be observed by a stereo-microscope. Furthermore,under transmission electron microscope, it also can be noted that the new blood vessel consisted of a monolayer of vascular endothelial cells with enlarged fissures,and the basal membrane was not intact. The expression of VEGF and bFGF was positive in xenografts on CAM, and VEGF was expressed at high levels constantly. Conclusions:The new blood vessels induced by tumors have pathologic and physiopathologic characteristics and many angiogenic factors are alm involved in the angiogenic process of OS-732. Furthermore, the application of angiogenic factors as a target in antiangiogenic therapy of osteosarcoma may be useful to improve the prognosis of patients with this disease.

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Objective To prepare a new kind of targeted liposome ultrasound contrast agent with small peptide K237 as the ligand which can combine specifically with KDR which is the main receptor of VEGF.and to test its capability in vitro. Methods Targeted bubbles(P-Bio-Av-Bio-Mbs) were formed through "biotin-avidin" bridge grafting, then they were incubated respectively with LOVO, HUVECs and LS174T which were KDR positive or negative expressed in various cells,meanwhile incubated LOVO cells with FITC- P-Bio-Av-Bio-Mbs,FITC-P-Mbs and FITC-Mbs respectively. After that, the rosette formation rate and fluorescence intensity of the combination between microbubbles and cells were observed with microscope and fluorescence microscope. After being incubated with small peptide K237 of 10 μg and 50 μg, LOVO cells were incubated with P-Bio-Av-Bio-Mbs for observing the distribution of microbubbles. Results In KDR sharply positive expressed LOVO cells, the surrounding rosette formation rate was as high as 90. 52% with the fluorescence intensity of grade 3, and it was 53. 46% with grade 2 fluorescence intensity rate in KDR positive expressed HUVECs cells, while in KDR negative expressed LS174T cells, there were few microbubbles surrounded with rosette formation rate of 5. 57% and fluorescence intensity rate of grade 0-1, therefore there were significant statistic differences in rosette formation rate among groups ( P < 0.05). After LOVO cells combined with FITC-P-Bio-Av-Bio-Mbs, FITC-P-Mbs and FITC-Mbs respectively,there were significant differences in their rosette formation rate, namely 89.62%, 7. 56% , 0 with the fluorescence rate of 3,0 - 1 and 0 respectively. Targeted cells pretreated with 10 pg K237 showed significant decreased rosette formation,and there was no formation in 50 ?g pretreated group. Conclusions KDR-Targeted liposome contrast agent with small peptide K237 liganded has been successfully prepared through biotin-avidin mediation and could combine specifically and high efficiently with targeted cells in vitro. The KDR-targeted molecular imaging of tumor neovascularizaiton may provide a new approach for early diagnosis of carcinoma.

Objective To screening optimized ultrasound (US)condition for MCF-7 cells and MCF-7/Tax cells,and to investigate the effect of dual-ligands nanoparticles (NPs ) combined with US on overcoming multidrug resistance (MDR).Methods To obtain optimized US condition,cell viability and cellular uptake of NPs treated with MCF-7 cells and MCF-7/Tax cells were detected under different ultrasonic parameters including ultrasound intensity,exposure duration and microbubble concentration. MTT assay was performed to observe the effect of NPs combined with US on cells.Results The optimal US conditions for MCF-7 cells was irradiation intensity 0.6 W/cm2 ,irradiation time 80 s,and the MBs concentration with volume ratio of microbubbles to medium was 1∶1 0;and for MCF-7/Tax cells,irradiation intensity 0.6 W/cm2 ,irradiation time 80 s,and the MBs concentration with volume ratio of microbubbles to medium was 1∶20.Compared with individual NPs,NPs assisted by US exhibited greater killing ability for MCF-7 (IC50 1 .43 ng/ml)and MCF-7/Tax cells (IC50<800 ng/ml).Conclusions US effect could enhance drug sensitivity of the dual-functionized NPs for MCF-7/Tax cells,indicating that US irradiation had potential assisted modality to reverse tumor MDR.

Objective:To evaluate the accuracy of two-dimensional ultrasound(2D-US), three-dimensional volume ultrasound (3D-US) and ultrasound strain elastography (USE) in the measurement of preoperative tumor size of breast cancer and its influencing factors.Methods:A total of 101 patients with breast cancer in Nanfang Hospital of Southern Medical University from April to November 2016 were recruited in this study. The maximum diameter of the lesion was examined by 2D-US 3D-US and USE before core needle biopsy or surgery biopsy. The Bland-Altman analysis and intraclass correlation coefficient (ICC) were used to analyze the consistency between the ultrasonic technique measurements and the pathological measurements of postoperative lesion. Chi-square test or Fisher exact test was used to analyze whether the accuracy of three imaging techniques was affected by different clinical pathologic factors and imaging characteristics.Results:3D-US showed better agreement with histology than 2D-US and USE, with a higher ICC (ICC 3D-US=0.90>ICC 2D-US=0.81>ICC SUE=0.78) and low variation. In 3D-US, the accuracy rate of the age >40 years old group was higher than ≤40 years old group. In 2D-US, the measurement accuracy of invasive ductal carcinoma (IDC) without intraductal carcinoma in situ (DCIS) group was higher than DCIS with DCIS group, non-microcalcifications group was more accurate than microcalcifications group. The long diameter of lesion ≤2 cm group was more accurate than >2 cm group, IDC group was more accurate than invasive lobular carcinoma(ILC) group. In USE, the measurement accuracy of IDC without DCIS group was higher than DCIS with DCIS group, non-microcalcifications group was more accurate than microcalcifications group. All the differences mentioned above were statistically significant(all P<0.05). Conclusions:For accurate measurement of the size of breast cancer lesions, 3D-US is the best, which is least affected by clinicopathological factors and imaging features, followed by 2D-US and USE. This has certain significance for clinically determining the extent of breast cancer lesions.