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OBJECTIVES@#Staphylococcus epidermidis (S. epidermidis) is a Gram-positive opportunistic pathogen that often causes hospital infections. With the abuse of antibiotics, the resistance of S. epidermidis gradually increases, and drug repurposing has become a research hotspot in the treating of refractory drug-resistant bacterial infections. This study aims to study the antimicrobial and antibiofilm effects of simeprevir, an antiviral hepatitis drug, on S. epidermidis in vitro.@*METHODS@#The micro-dilution assay was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of simeprevir against S. epidermidis. Crystal violet staining assay was used to detect the biofilm inhibitory effect of simeprevir. The antimicrobial activity of simeprevir against S. epidermidis and its biofilm were explored by SYTO9/PI fluorescent staining. The combined effect between simeprevir and gentamycin was assessed by checkerboard assay and was confirmed by time-inhibition assay.@*RESULTS@#Simeprevir showed significant antimicrobial effects against S. epidermidis type strains and clinical isolates with the MIC and MBC at 2-16 μg/mL and 4-32 μg/mL, respectively. The antimicrobial effects of simeprevir were confirmed by SYTO9/PI staining. Simeprevir at MIC could significantly inhibit and break the biofilm on cover slides. Similarly, simeprevir also significantly inhibit the biofilm formation on the surface of urine catheters either in TSB [from (0.700±0.020) to (0.050±0.004)] (t=54.03, P<0.001), or horse serum [from (1.00±0.02) to (0.13±0.01)] (t=82.78, P<0.001). Synergistic antimicrobial effect was found between simeprevir and gentamycin against S. epidermidis with the fractional inhibitory concentration index of 0.5.@*CONCLUSIONS@#Simeprevir shows antimicrobial effect and anti-biofilm activities against S. epidermidis.
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Humans , Simeprevir , Antiviral Agents , Anti-Bacterial Agents/pharmacology , Cross Infection , GentamicinsABSTRACT
Objective:To investigate the mechanism of histidine kinase AgrC in Staphylococcusaureus biofilm formation enhancements under a environment with sub-minimal inhibitory concentration (sub-MIC) ciprofloxacin, aiming to shed new light on the antibiotic treatment for S. aureus biofilm-related infections. Methods:Clinical isolates were collected from the skin tissue and body fluid samples at the Department of Medicine Clinical Laboratory, the Third Xiangya Hospital of Central South University in 2021. Microdilution broth method was used for determining the minimum inhibitory concentration (MIC). Biofilm assays were performed by using crystal violet staining assay and SYTO9 and PI fluorescent dye staining. Reverse transcription real-time fluorescence quantitative PCR (qRT-PCR) was used to assess the transcriptional levels of the biofilm regulatory genes ( agrC, agrA, icaA and icaR) of S. aureus treated with different sub-MIC concentrations of ciprofloxacin. Isothermal titration calorimetry (ITC) was used to analyze the binding affinity of ciprofloxacin to histidine kinase AgrC. The data setwere presented as xˉ±s, analysis of variance or nonparametric test is used based on the distribution and homogeneity of variance of the data set. P<0.05 indicates statistically significant differences. Results:The MIC of ciprofloxacin against S. aureus was 0.25-0.5 mg/L. Ciprofloxacin could significantly promote the ability of S. aureus biofilm formation at the concentration of 1/4 × MIC [ATCC 43300( t=7.42, P=0.002), SA1( t=5.42, P=0.005), SA2( t=6.38, P=0.002), SA3( t=4.8, P =0.009), SA4( t=7.06, P=0.002) and SA5( t=4.36, P=0.004)]. The result of fluorescent staining showed that sub-MIC of ciprofloxacin could significantly promote the biofilm formation of S. aureus. The result of qRT-PCR suggested that there was no significant change in agrC gene expression, but the expression level of agrA ( t=4.42, P=0.003) and icaR ( t=4.49, P=0.007) was significantly decreased in the presence of sub-MIC ciprofloxacin [(0.61±0.24) and (0.56±0.12)], and the expression level of icaA was increased [1.51±0.19( t=5.24, P=0.009)].The result of ITC showed that ciprofloxacin had a significantly high affinity with AgrC. Conclusion:Sub-MIC of ciprofloxacin could promote the biofilm formation of S. aureus and increase its antibiotic resistance by binding to the AgrC protein receptor and affecting the expression of a grA, icaA and icaR genes.
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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.
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Objective:To explore the application value of conventional ultrasound(US) in detecting occult bleeding lesions in joints of patients with hemophilia.Methods:Twenty-seven children with severe hemophilia A who received factor Ⅷ prophylactic treatment from March 2017 to April 2018 in Nanfang Hospital, Southern Medical University were enrolled. Clinical data were collected from routine practice accompanied with US examination, hemophilia joint health score (HJHS) 2.1 assessment and the history of hemarthrosis of both ankles, elbows and knees at baseline and at 1 year follow-up.Results:A total of 157 joints of 27 patients were followed up for one year. During the treatments, 74 joints were found without history of hemarthrosis, among which the total US score of 14(14/74, 18.9%) joints increased, and HJHS 2.1 score of 11(11/74, 14.9%) joints developed. There was no significant change in the HJHS 2.1 score of 108 joints, among which 25 joints (25/108, 23.1%) had an increase in the total US score.However, there was no significant change in the total US score for 93 joints, of which 9(9/93, 9.7%) had an increase in HJHS 2.1 score.Conclusions:US examination can sensitively detect hemophilia arthropathy in joints without history of hemarthrosis and without obvious progression of arthropathy by HJHS 2.1 examination, and provide clinicians with more accurate joint information.
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Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS
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Tuberculosis (TB) is an infectious fatal disease that seriously endangers human health worldwide.Isoniazid (INH) is an important first-line drug for TB, but it can cause serious adverse drug reactions, such as liver injury and even liver failure.At present, it is believed that metabolites of INH, imbalance of oxidative stress responses and immune response disorders are major causes of INH induced liver injury.In addition, involved genes and gene polymorphisms are susceptible to liver injury caused by INH.In this paper, the association of INH induced liver injury with the polymorphisms of genes related to INH metabolizing enzymes, as well as oxidative stress and immune responses are summarized to improve the understanding of INH induced liver injury and provide novel directions for its prevention and treatment.
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Objective:To evaluate the ability of Sysmex urine automatic analyzer UF-5000 to detect renal tubular epithelial cells, and to explore the value of detection of renal tubular epithelial cells in renal tubular injury of diabetes mellitus.Methods:Case control study. 452 urine samples were collected from the third Xiangya Third Hospital of Central South University from October 2018 to April 2019 (252 in the control group, 113 in diabetes without renal injury group and 87 in diabetes with renal injury group). All samples were detected by both UF-5000 and microscopic examination, established reference range for normal population, then contrasted the coincidence rate and uniformity of the two methods, to evaluate the ability of urine automatic analyzer UF-5000 to detect renal tubular epithelial cells, and the diagnostic value of tubular epithelial cells for renal tubular injury in diabetic patients. All statistical analyses were performed using SPSS17.0, Kappa consistency analysis, ROC curve analysis, Kruskal-Wallis test and Chi-square test were used.Results:The reference range of renal tubular epithelial cells by Sysmex urine automatic analyzer UF-5000 is 0-1.7/μl. The results of the two methods were analyzed by Kappa consistency analysis. The Kappa value was 0.699, P>0.05, which meant highly consistent. ROC curve analysis showed when cut-off value was 1.7/μl. The sensitivity, specificity and area under ROC curve were 0.791, 0.817 and 0.861 respectively. The median of renal tubular epithelial cells was 0.4/μl, 2.0/μl and 2.3/μl in the healthy control group, the diabetes without renal injury group and the diabetes with renal injury group, respectively; the positive rate of renal tubular epithelial cells in the three groups were 2.78%, 56.64% and 75.86% respectively. Compared with the control group, the median and positive rate of renal tubular epithelial cells in the diabetes without renal injury group and the diabetes with renal injury group were significant different; there was also significant difference in the positive rate of renal tubular epithelial cells between the two groups. Conclusion:Compared with the control group, the positive rate of urine renal tubular epithelial cells indiabetes without renal injury group is significantly higher, which is helpful to detect renal tubular injury, to carry out early intervention and to prolong the time of progression to chronic kidney disease.
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OBJECTIVE@#To explore the feasibility of radiomics for predicting lymph node metastasis in the central region of the neck in patients with thyroid papillary carcinoma (PTC).@*METHODS@#A total of 189 patients with PTC confirmed by thyroid fine needle aspiration biopsy were prospectively enrolled in this study. The cross-sectional and longitudinal ultrasound images and the images of both sections were analyzed for predicting central lymph node metastasis using a radiomics approach with pathological results as the gold standard.@*RESULTS@#In the 189 patients, the accuracy, sensitivity and specificity of preoperative thyroid ultrasonography for diagnosis of central lymph node metastasis was 69.39%, 64% and 73%, respectively. Based on the ultrasound images of the cross-sections, longitudinal sections and both sections, the accuracy, sensitivity and specificity of radiomics for predicting central lymph node metastasis was 66.06%/68.12%/77.69%, 53%/46%/40%, and 52%/53%/51%, respectively.@*CONCLUSIONS@#Radiomics with combined analysis of the ultrasound images on the cross-section and longitudinal section images achieves a higher accuracy for predicting central lymph node metastasis than analysis a single section, and its diagnostic accuracy is much higher than that of conventional ultrasound examination.
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Humans , Carcinoma, Papillary , Diagnostic Imaging , Pathology , Image Interpretation, Computer-Assisted , Lymph Nodes , Lymphatic Metastasis , Diagnostic Imaging , Neck , Prospective Studies , Thyroid Neoplasms , Diagnostic Imaging , Pathology , UltrasonographyABSTRACT
Objective To prepare dual-targeted pH-sensitive DOX prodrug-microbubble complex and explore the characterization of complex with ultrasound as well as drug release in vitro . Methods Dual-targeted ligands ,cRGD and folate were conjugated with heparin using carbodiimide method ,and then the dual-targeted pH-sensitive DOX prodrug was synthesized by coupling DOX via a pH-sensitive hydrazone bond . The prodrug was combined with microbubbles to prepare complex by biotin-avidin system . The characterization of complex with/without ultrasound was investigated for size ,morphology and drug loaded capacity .In vitro drug release manner of complex with/without at different pH was analyzed . Results DOX content of the prodrug determined by UV Spectrophotometry was about 18 .9％ . Dynamic laser light scattering analysis( DLS) ,corresponding to transmission electron microscope( TEM ) findings ,revealed its inhomogeneous size distribution [ mean size ( 159 .7 ± 24 .5) nm and ( 1089 .0 ± 174 .9) nm ] . However ,the complex was dispersed into uniform fragment after ultrasound irradiation [ mean size ( 155 .9 ± 29 .8) nm , polymer dispersity index( PDI) 0 .22 ,Zeta potential - ( 20 .6 ± 3 .4) mV ] . The cumulative release rate of DOX from both complex and complex with ultrasound at pH 5 .0 were much faster than that at pH 7 .4 , displaying a pH-triggered release manner . Conclusions Dual-targeted pH-sensitive DOX prodrug-microbubble complex displays excellent drug release activity in acid environment . Uniform fragment and smaller particle size of complex could be achieved via ultrasound irradiation ,promoting DOX accumulation within tumor tissue and facilitating in vivo antitumor ability .
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Objective To explore the diagnostic and score value of ultrasound on hemophiliac arthropathy referring to MRI on the diagnosis and score of hemophiliac arthropathy Methods The ultrasound and MRI examinations were performed on 42 joints of 42 hemophilia patients 14 knees 14 ankles and 14 elbows The consistency of ultrasound and magnetic resonance imaging in the detection and score of joint diseases was compared Finally inter-and intra-observer agreement of ultrasound scoring system were tested Results The consistency of ultrasound and magnetic resonance imaging was excellent κ=0 763-0 896 P < 0 001 in the detection of early soft tissue lesions effusion or hemarthrosis synovial hypertrophy hemosiderin excellent κ=0 793 P <0 001 in the detection of cartilage loss poor κ=0 133 P = 0 132 in the detection of erosions and poor κ= 0 100 P = 0 137 in the detection of subchondral cysts The consistency of ultrasound and magnetic resonance imaging was good to excellentκ=0 684-0 833 P < 0 001 in the score of early soft tissue lesions effusion or hemarthrosis synovial hypertrophy and hemosiderin and poor to good κ=0 145 -0 635 P <0 001 in the score of advanced osteochondral lesions cartilage loss and bone erosions The inter-observer agreement was good to excellent κ=0 676-0 870 P <0 001 for early soft tissue lesions and moderate to excellent κ=0 421- 0 75 1 P < 0 001 for advanced osteochondral lesions The intra-observer agreement was good to excellent κ=0 705-0 885 P <0 001 for early soft tissue lesions and moderate to good κ=0 532 -0 732 P <0 001 for advanced osteochondral lesions Conclusions Ultrasound plays an important role in detecting early soft tissue changes effusion or hemarthrosis synovial hypertrophy hemosiderin and cartilage loss which helps follow-up and guide clinical treatment.
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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.
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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.
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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.
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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.
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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.
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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.
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Course center is the communion platform with superior resources for course management,course construction andcourse learning.Course center includes course center information display subsystem,course assistant teaching subsystem based onnetwork,teaching resource storage subsystem,superexcellent course network construction subsystem and teacher preparing for lessonsoff-line subsystem(Skyone).Constructing course center can promote college teaching work development socially,modernly,informationally,standardly and accelerate teaching quality upgrade.
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<p><b>OBJECTIVE</b>To study angiogenesis and the expression of nm23-H(1) tumor metastatic suppressor gene in primary breast carcinoma and their relationship with axillary lymph node metastasis.</p><p><b>METHODS</b>Intratumoral vascularization in 80 cases of breast cancer was observed preoperatively by power doppler imaging (PDI) and analysed with computer-assisted quantative assessment, and the expression of microvessel density (MVD) and nm23 protein was determined by immunohistochemical technique.</p><p><b>RESULTS</b>Blood flow signals and blood vessels postitive area within masses were more in axillary node positive (LN+) group than in axillary node negative (LN-) group (t = 7.07, P < 0.01), MVD expression were higher in the LN+ group than in the LN- group (t = 6.34, P < 0.01). Meanwhile the expression of nm23-H(1) protein was lower in the LN+ group than in the LN- group, and significant correlation was found between angiogenesis and the expression of nm23-H(1) protein.</p><p><b>CONCLUSIONS</b>Angiogenesis and the expression of nm23-H(1) protein may play an important role in the lymphatic metastasis process of breast cancer. Furthermore, angiogenesis may correlates with the expression of nm23-H(1) protein in that progress.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Axilla , Biomarkers, Tumor , Breast Neoplasms , Diagnosis , Metabolism , Pathology , Genes, Tumor Suppressor , Lymph Nodes , Pathology , Lymphatic Metastasis , Diagnosis , Monomeric GTP-Binding Proteins , NM23 Nucleoside Diphosphate Kinases , Neovascularization, Pathologic , Nucleoside-Diphosphate Kinase , Transcription FactorsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of anti-VEGF antibody on angiogenesis induced by osteosarcoma OS-732 cell line and tumor growth.</p><p><b>METHODS</b>With a tumor model on the chick embryo chorioallantoic membrane (CAM), the inhibition of angiogenesis and tumor growth by anti-VEGF antibody were observed under a stero-microscope and a light microscope. Furthermore, the proliferation and apoptosis in tumor cells and endothelial cells (EC) were studied by TdT-mediated duTP nick and labeling (TUNEL) and immunohistochemical staining using proliferating cell nuclear antigen (PCNA) monoclonal antibody.</p><p><b>RESULTS</b>VEGF polyclonal antibody administration in tumor-bearing chick embryo resulted in growth arrest of xenografts and a markedly reduction in the new capillaries which converged upon the tumor. The tumor cell apoptotic index was higher in the anti-VEGF antibody treated group than the negative control group, but the proliferation index was not significantly different between them. At the same time, increased apoptosis and decreased proliferation in EC were also noted.</p><p><b>CONCLUSION</b>VEGF polyclonal antibody is able to inhibit the angiogenesis induced by OS-732 obviously, probably by the mechanism of inhibition of EC proliferation and promotion of their apoptosis, furtherly, which may contribute to the apoptosis of tumor cells and result in suppression of tumor growth.</p>
Subject(s)
Animals , Chick Embryo , Antibodies , Therapeutic Uses , Apoptosis , Bone Neoplasms , Therapeutics , Cell Division , Disease Models, Animal , Endothelial Growth Factors , Allergy and Immunology , Endothelium, Vascular , Cell Biology , Immunotherapy , Lymphokines , Allergy and Immunology , Microscopy , Neovascularization, Pathologic , Osteosarcoma , Therapeutics , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
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.