1.A Method to Quantify Breast MRI for Predicting Tumor Invasion in Patients with Preoperative Biopsy- Proven Ductal Carcinoma in Situ (DCIS).
Myung Su KO ; Sung Hun KIM ; Bong Joo KANG ; Byung Gil CHOI ; Byung Joo SONG ; Eun Suk CHA ; Atilla Peter KIRALY ; In Seong KIM
Journal of the Korean Society of Magnetic Resonance in Medicine 2013;17(2):73-82
PURPOSE: To determine the quantitative parameters of breast MRI that predict tumor invasion in biopsy-proven DCIS. MATERIALS AND METHODS: From January 2009 to March 2010, 42 MRI examinations of 41 patients with biopsy-proven DCIS were included. The quantitative parameters, which include the initial percentage enhancement (E1), peak percentage enhancement (E(peak)), time to peak enhancement (TTP), signal enhancement ratio (SER), arterial enhancement fraction (AEF), apparent diffusion coefficient (ADC) value, long diameter and the volume of the lesion, were calculated as parameters that might predict invasion. Univariate and multivariate analyses were used to identify the parameters associated with invasion. RESULTS: Out of 42 lesions, 23 lesions were confirmed to be invasive ductal carcinoma (IDC) and 19 lesions were confirmed to be pure DCIS. Tumor size (p = 0.003; 6.5 +/- 3.2 cm vs. 3.6 +/- 2.6 cm, respectively) and SER (p = 0.036; 1.1 +/- 0.3 vs. 0.9 +/- 0.3, respectively) showed statistically significant high in IDC. In contrast, E1, Epeak, TTP, ADC, AEF and volume of the lesion were not statistically significant. Tumor size and SER had statistically significant associations with invasion, with an odds ratio of 1.04 and 22.93, respectively. CONCLUSION: Of quantitative parameters analyzed, SER and the long diameter of the lesion could be specific parameter for predicting invasion in the biopsy-proven DCIS.
Breast
;
Carcinoma in Situ
;
Carcinoma, Ductal
;
Carcinoma, Intraductal, Noninfiltrating
;
Diffusion
;
Humans
;
Lymphokines
;
Magnetic Resonance Imaging
;
Multivariate Analysis
;
Odds Ratio
;
Thymine Nucleotides
2.Local tissue hypoxia and formation of nasal polyps.
Shu JIANG ; Zhen DONG ; Dongdong ZHU ; Zhanquan YANG
Chinese Medical Journal 2003;116(2):243-247
OBJECTIVETo explore the response of nasal mucosa epithelial cells to hypoxia in terms of formation of nasal polyps (NP).
METHODSEpithelial cells of NP and inferior turbinate (IT) were cultured serum-free under normal oxygen and hypoxic circumstances with stimulation of IL-1 beta and TNF alpha. The vascular endothelial growth factor (VEGF) mRNA and VEGF protein levels of the cultured cells were detected using in situ hybridization and ELISA, respectively.
RESULTSThe expression of VEGF mRNA was significantly higher in epithelial cells of NP than in IT exposed to pro-inflammatory cytokines or hypoxia (P < 0.01). VEGF levels were higher in NP epithelial cells than those of IT (P < 0.01) under hypoxia.
CONCLUSIONVEGF-induced by hypoxia is very important for the early stages of forming polyps.
Cell Hypoxia ; physiology ; Cells, Cultured ; Endothelial Growth Factors ; genetics ; Enzyme-Linked Immunosorbent Assay ; Erythropoietin ; genetics ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; Interleukin-1 ; pharmacology ; Lymphokines ; genetics ; Nasal Mucosa ; metabolism ; Nasal Polyps ; etiology ; metabolism ; RNA, Messenger ; analysis ; Tumor Necrosis Factor-alpha ; pharmacology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
3.The in vitro isolation, culture and transfection of human fetal epidermal stem cells.
Guo-Bin DING ; Bi CHEN ; Jun-Tao HAN ; Chao-Wu TANG ; Bo-Tao WANG
Chinese Journal of Burns 2003;19(1):18-21
OBJECTIVETo explore the in vitro methods of isolation and culture of human fetal epidermal stem cells (HFESCs) and the feasibility of the cultured cells as the target cells for gene transfection.
METHODSThe HFESCs were isolated by means of type IV collagen rapid adhering method. The culture medium for HFESCs was prepared according to that for human fetal fibroblasts. The cultured cells were identified by immunohistochemistry staining of keratin-19 and integrin-beta1, cell cycle analysis and clone forming rate determination. Then the cultured cells were gene transfected in vitro by liposome mediating method in which eukaryon expression vector pcDNA3.1/VEGF165 containing vascular endothelial growth factor 165 (VEGF165) were transfected into cultured cells, or by virus vector mediating method in which recombinant adenovirus accompanied vector (raav) containing green fluorescent protein (GFP) (raav/GFP) were transfected into the cultured cells, respectively. The results of in vitro gene transfection of HFESCs were observed by immunohistochemisty staining and fluorescence microscope.
RESULTSHFESCs grew well and formed large clones with higher cloning efficiency and higher ratio of G1 cells than keratinocytes. The cultured cells were strongly positive with immunohistochemistry staining of keratin-19 and integrin-beta1. After being gene-transfected by pcDNA3.1/VEGF165, the VEGF165 of HFESCs showed positive immunohistochemistry staining property, while the HFESCs transfected by raav/GFP exhibited strong fluorescence.
CONCLUSIONHFESCs could be isolated and cultured in vitro by means of rapid adherence to type IV collagen. It seemed feasible that HFESCs were gene transfected with liposome or adeno-associated virus as the vector.
Cell Adhesion ; Cell Cycle ; physiology ; Cells, Cultured ; Endothelial Growth Factors ; genetics ; metabolism ; Epidermis ; Fetus ; G1 Phase ; Green Fluorescent Proteins ; Humans ; Immunohistochemistry ; Integrin beta1 ; analysis ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Keratinocytes ; cytology ; Keratins ; analysis ; Luminescent Proteins ; genetics ; metabolism ; Lymphokines ; genetics ; metabolism ; Microscopy, Fluorescence ; Plasmids ; genetics ; Stem Cells ; chemistry ; cytology ; metabolism ; Transfection ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
4.Microvessel density, epithelial-stromal vascular cuffing and expression of vascular endothelial growth factor in human cervical carcinoma.
Ji-Fen YAO ; Yin-Fen JI ; Yi-Fu SHI
Journal of Zhejiang University. Medical sciences 2003;32(1):62-66
OBJECTIVETo observe microvessel density(MVD), epithelial stromal vascular cuffing(VC) and expression of vascular endothelial growth factor(VEGF) in human cervical carcinomas and to clarify their significance in the invasion and metastasis of cervical carcinoma.
METHODSVEGF and CD34 were stained immunohistochemically (SP) in 57 cases of cervical carcinoma (30 cases of squamous cell carcinoma, 20 of adenocarcinoma 7 of glandular and squamous cell carcinoma), 29 cases of cervical intraepithelial neoplasia (CIN) and 16 cases of normal cervices, meanwhile, MVD and VC were also assayed.
RESULTSThere were significant differences among the above 5 groups for MVD P<0.01 . The VC pattern showed a significant difference between cervical carcinoma and CIN or control group P<0.01). The positive rates of VEGF in normal cervical epithelium, CIN, squamous cell carcinoma, adenocarcinoma, glandular and squamous cell carcinoma were 18.8% 3/16, 82.8% 24/29), 93.3% 28/30), 100% 20/20 and 7/7(100%), respectively. There were significant differences between these cervical lesion groups and the control group(P<0.001). The MVD showed significant differences between the positive pelvic node metastasis and negative pelvic node metastasis P<0.05). There was no significant correlation between the expression of VEGF and the tumor diameter, clinical stage, pathologic grade and pelvic node metastasis.
CONCLUSIONThe expression of VEGF may play an important role in the angiogenesis of cervical carcinoma. Degree of malignancy of cervical carcinoma has a close association with microvessel density.
Adult ; Aged ; Aged, 80 and over ; Endothelial Growth Factors ; analysis ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; Lymphatic Metastasis ; Lymphokines ; analysis ; Microcirculation ; Middle Aged ; Uterine Cervical Neoplasms ; blood supply ; chemistry ; pathology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
5.Study on angiogenesis of multiple myeloma in vitro.
Wen-Ming CHEN ; Yin WU ; Jia-Zhi ZHU ; Jeannette SORIA ; Massoud MIRSHAHI
Journal of Experimental Hematology 2002;10(4):310-314
Angiogenesis is a necessary step in tumor progression, and it correlates an unfavorable prognosis. In multiple myeloma, bone marrow microvessel density and angiogenesis grading correlated with plasma cell labeling index and are poor survival predictors, but the study of myeloma's angiogenesis is very rare. This article was to study the effect of multiple myeloma cell line conditioned media on the proliferation, migration and angiogenesis of human bone marrow endothelial cells (HBMEC). The multiple myeloma cell line conditioned media were obtained by using RPMI 1640 media containing 2% fetal bovine serum (FBS) to cultivate myeloma cell lines for 18 hours. Proliferation and migration of HBMEC were detected by using those media to cultivate HBMEC. Capillary tube formation was performed by using microcarriers cytodex-3 covered with HBMEC in three-dimensional fibrin matrices. The results showed that myeloma conditioned media induced HBMEC's proliferation and migration (P < 0.001), and those media induced capillary tube formation (length and width) of HBMEC (P < 0.001). It was concluded that myeloma cell lines induce HBMEC's proliferation, migration, and capillary tube formation by secreting several cytokines.
Bone Marrow Cells
;
cytology
;
Cell Division
;
Cell Movement
;
Endothelial Growth Factors
;
analysis
;
physiology
;
Humans
;
Intercellular Signaling Peptides and Proteins
;
analysis
;
physiology
;
Lymphokines
;
analysis
;
physiology
;
Multiple Myeloma
;
blood supply
;
chemistry
;
pathology
;
Neovascularization, Pathologic
;
etiology
;
Vascular Endothelial Growth Factor A
;
Vascular Endothelial Growth Factors
6.Vascular endothelial growth factor promotes hematogenous metastasis of cancer cells in patients with non-small cell lung cancer.
Qianggang DONG ; Jiuxian FENG ; Jinsu HUANG ; Guoliang BAO ; Huifang SHA ; Weiyong GU
Chinese Journal of Oncology 2002;24(2):142-146
OBJECTIVETo evaluate the effect of vascular endothelia1 growth factor (VEGF) on the hematogenous metastasis of non-small cell lung cancer (NSCLC).
METHODSThe identification of lung cancer cells in the peripheral blood were carried out by cytological, immunohistocytologica1 and immunofluorecent stains respectively, following isolation of cytokeratin-expressing cells with magnetic activated cell sorting. The quantification of cancer cells in the blood was performed according to the established flow cytometric assay. The plasma VEGF was measured by commercially available ELISA kit.
RESULTSThe lung cancer cells in the blood, showing a remarkable nuclear polymorphism, expressed the epithelial marker cytokeratin and telomerase reverse transcriptase (hTERT). These cells were stained positive by an NSCLC-specific monoclonal antibody S5Al0-2, but negative by antibodies against CD34 and CD45 antigens. Using the flow cytometric assay, 44 cases (28.6%) of l54 NSCLC patients were found to have cancer cells in their blood, with the incidence of positive cases correlated with the stage of disease. The plasma VEGF level was significantly increased in NSCLC patients in comparison with healthy individuals and patients with benign pulmonary diseases. This level was correlated with the stages of disease in patients with adenocarcinoma. In patiens with cancer cells in their blood, a higher level of plasma VEGF was related with an increased number of cancer cells.
CONCLUSIONThe plasma VEGF level is increased in NSCLC patients with approximate1y one fourth to have cancer cells in the peripheral blood. In these patients, increased VEGF level promotes hematogenous tumor metastasis, as indicated by a much higher number of cancer cells in the blood.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; blood ; pathology ; DNA-Binding Proteins ; Endothelial Growth Factors ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Keratins ; analysis ; Lung Neoplasms ; blood ; pathology ; Lymphokines ; blood ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; chemistry ; pathology ; Telomerase ; analysis ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
7.Expression of VEGF, EGFR, p16 in lip cancers and oral squamous cell carcinomas and their clinic significance.
Wenjun YANG ; Zhaoquan LIN ; Liangzhong LI ; Guoshan ZHANG
Chinese Journal of Stomatology 2002;37(2):99-101
OBJECTIVETo detect the expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), p16 protein in lip cancers and oral squamous cell carcinoma (OSCC) as well as their clinicopathological significance.
METHODSImmunohistochemisty for expression VEGF, EGFR, P16 were carried out in 69 cases of lip cancers and OSCC.
RESULTSExpression of VEGF, EGFR, p16 protein in OSCC and lip cancers was respectively 71.01%, 46.37%, 28.98% and there were no significance between their positive expressions (P > 0.05) as well as in different sites of them (P > 0.05). Expression of VEGF was respectively 71.01% in cancers and 10.00% in non-tumor tissues, there was statistic significance among those (P < 0.05).
CONCLUSIONSThe results show that there is no correlation to the expression of VEGF, EGFR and P16 protein in OSCC and lip cancers. It is suggests that the expression of VEGF might become one of the useful markers for OSCC.
Adult ; Aged ; Carcinoma, Squamous Cell ; chemistry ; pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; analysis ; Endothelial Growth Factors ; analysis ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; analysis ; Lip Neoplasms ; chemistry ; pathology ; Lymphokines ; analysis ; Male ; Middle Aged ; Mouth Neoplasms ; chemistry ; pathology ; Receptor, Epidermal Growth Factor ; analysis ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
8.Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA.
Jin Ok JEONG ; Jong Hoe BYUN ; Eun Seok JEON ; Hyeon Cheol GWON ; Young Shin LIM ; Jang Won PARK ; Seon Ju YEO ; Young Joo LEE ; Sun Young KIM ; Duk Kyung KIM
Experimental & Molecular Medicine 2002;34(4):278-284
Direct injection of the vascular endothelial growth factor (VEGF) gene plasmid DNA into the myocardium was shown to induce development of new blood vessels to increase the circulation in the heart of patients with coronary artery diseases. However, such angiogenic gene therapy (via naked DNA) was limited by low level of gene expression. Furthermore, the temporal and spatial characteristics of VEGF gene transfer in the heart are not known. In this study, we demonstrated that a plasmid vector, containing the human cytomegalovirus immediate early (HCMV IE) promoter and enhancer, induces greater expression of gene in the rat heart monitored by gene fused to the chloramphenicol acetyl transferase (CAT) reporter, than four different viral and cellular promoters. Interestingly, expression of VEGF121 protein showed an earlier peak, a shorter duration, and a wider distribution than that of CAT only. Therefore, a plasmid vector with an HCMV IE promoter/enhancer provides clear advantages over other previously developed plasmids. Furthermore, expression profile of VEGF121 gene may provide useful information in the design of angiogenic gene therapy in the heart
Animals
;
Chloramphenicol O-Acetyltransferase/analysis/genetics
;
Comparative Study
;
Cytomegalovirus/*genetics
;
DNA, Viral/*administration & dosage/*genetics
;
Endothelial Growth Factors/analysis/*genetics
;
*Enhancer Elements (Genetics)
;
Gene Expression Regulation, Viral
;
Gene Fusion
;
*Gene Transfer Techniques
;
Genes, Viral
;
Genetic Vectors
;
Intercellular Signaling Peptides and Proteins/analysis/*genetics
;
Lymphokines/analysis/*genetics
;
Male
;
Myocardium/*metabolism
;
Plasmids/genetics
;
*Promoter Regions (Genetics)
;
Rats
;
Rats, Sprague-Dawley
;
Time Factors
;
Vascular Endothelial Growth Factor A
;
Vascular Endothelial Growth Factors
9.Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA.
Jin Ok JEONG ; Jong Hoe BYUN ; Eun Seok JEON ; Hyeon Cheol GWON ; Young Shin LIM ; Jang Won PARK ; Seon Ju YEO ; Young Joo LEE ; Sun Young KIM ; Duk Kyung KIM
Experimental & Molecular Medicine 2002;34(4):278-284
Direct injection of the vascular endothelial growth factor (VEGF) gene plasmid DNA into the myocardium was shown to induce development of new blood vessels to increase the circulation in the heart of patients with coronary artery diseases. However, such angiogenic gene therapy (via naked DNA) was limited by low level of gene expression. Furthermore, the temporal and spatial characteristics of VEGF gene transfer in the heart are not known. In this study, we demonstrated that a plasmid vector, containing the human cytomegalovirus immediate early (HCMV IE) promoter and enhancer, induces greater expression of gene in the rat heart monitored by gene fused to the chloramphenicol acetyl transferase (CAT) reporter, than four different viral and cellular promoters. Interestingly, expression of VEGF121 protein showed an earlier peak, a shorter duration, and a wider distribution than that of CAT only. Therefore, a plasmid vector with an HCMV IE promoter/enhancer provides clear advantages over other previously developed plasmids. Furthermore, expression profile of VEGF121 gene may provide useful information in the design of angiogenic gene therapy in the heart
Animals
;
Chloramphenicol O-Acetyltransferase/analysis/genetics
;
Comparative Study
;
Cytomegalovirus/*genetics
;
DNA, Viral/*administration & dosage/*genetics
;
Endothelial Growth Factors/analysis/*genetics
;
*Enhancer Elements (Genetics)
;
Gene Expression Regulation, Viral
;
Gene Fusion
;
*Gene Transfer Techniques
;
Genes, Viral
;
Genetic Vectors
;
Intercellular Signaling Peptides and Proteins/analysis/*genetics
;
Lymphokines/analysis/*genetics
;
Male
;
Myocardium/*metabolism
;
Plasmids/genetics
;
*Promoter Regions (Genetics)
;
Rats
;
Rats, Sprague-Dawley
;
Time Factors
;
Vascular Endothelial Growth Factor A
;
Vascular Endothelial Growth Factors
10.Correlation between epidermal growth factor and overexpression of vascular endothelial growth factor in hepatocellular carcinoma.
Gengwen HUANG ; Lianyue YANG ; Jianqing YANG ; Heli LIU ; Zhili YANG
Chinese Journal of Oncology 2002;24(6):564-566
OBJECTIVETo investigate the correlation between epidermal growth factor (EGF) and overexpression of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC).
METHODSExpressions of EGF, VEGF and microvessel density were studied through immunohistochemical SABC method in 36 HCC specimens, their paraneoplastic liver tissues and 6 normal liver tissues with the correlation between these parameters analyzed. Recombinant human EGF was used to stimulate HepG(2) cells and semi-quantitative reverse transcription PCR was adopted to detect the expression of VEGF in HepG(2) cells.
RESULTSThe positive rates of EGF and VEGF expression in HCC tissue were 75.0% and 88.9%. There was positive correlation between EGF and VEGF expression (P < 0.01, r = 0.462). Recombinant human EGF could induce the expression of VEGF in HepG(2) cells in a dose and time dependent manner.
CONCLUSIONThe expression of EGF in HCC underlies the overexpression of VEGF in HCC.
Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; Endothelial Growth Factors ; analysis ; Epidermal Growth Factor ; analysis ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; Liver Neoplasms ; metabolism ; Lymphokines ; analysis ; Male ; Middle Aged ; Neovascularization, Pathologic ; Statistics as Topic ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

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