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

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

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

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

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

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

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

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

OBJECTIVETo observe the effective mechanism and side effects of thalidomide to multiple myeloma (MM).

METHODSTen cases of MM were studied, of which 3 were previously untreated and 7 refractory or relapsed. Bone marrow microvascular density (MVD) was detected by factor-VIII related antigen and CD(34) immunohistological staining and serum concentration of vascular endothelial growth factor (VEGF) before and after treatment was determined by ELISA. The initial dosage of thalidomide was 100 approximately 200 mg/d with a weekly escalation of 50 mg/d to 450 approximately 650 mg/d. The therapeutic effectiveness is classified into partial remission, improvement and uneffective according to the decrease of serum M protein and bone marrow myeloma cells. Anemia, renal function and blood electrolytes were also observed.

RESULTSBefore treatment, MVD was 73.32 +/- 28.80 and 32.30 +/- 12.50 in MM and control group, respectively, (P < 0.01). MVD in MM group decreased to 56.12 +/- 19.34 after treatment, and was of significant difference (P < 0.05) as compared to the pretreatment value. However, there was still a significant difference as compared to control (56.12 +/- 19.34 vs 32.30 +/- 12.50, P < 0.01). The concentration of VEGF significantly decreased after treatment [from (178.23 +/- 26.56) ng/L to (78.48 +/- 19.98) ng/L, P < 0.01)]. The total effective rate was 70%. There were no serious side effects.

CONCLUSIONMVD and VEGF concentration were decreased obviously by thalidomide treatment. The dosage of 450 approximately 650 mg/d might be effective in refractory or initial MM.

Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antigens, CD34 ; analysis ; Bone Marrow ; blood supply ; drug effects ; Constipation ; chemically induced ; Endothelial Growth Factors ; blood ; Fatigue ; chemically induced ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; blood ; Lymphokines ; blood ; drug effects ; Male ; Middle Aged ; Multiple Myeloma ; blood ; drug therapy ; pathology ; Nausea ; chemically induced ; Sleep Wake Disorders ; chemically induced ; Thalidomide ; adverse effects ; therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; von Willebrand Factor ; analysis

OBJECTIVETo detect the biological factor association with metastasis and recurrence of hepato cellular carcinoma (HCC).

METHODSLabeled streptavidin biotin method was performed to study VEGF, uPA and ICAM-1 protein, and antigen of PCNA expression in 123 patients with HCC. Venous invasion was observed under microscope at the same time.

RESULTSThe expression rate of VEGF was higher in HCC with intra-hepatic metastasis in group B than in HCC without PVTT/metastasis in group A (P < 0.01) and higher in HCC with PVTT in group C and PVTT in group D higher than in group B (P < 0.05). The expression rate of uPA protein was higher in group B than in group A (P < 0.01), but no significant difference in groups B and C. The expression rate of ICAM-1 showed no significant difference in the four groups. MVD and PCNA-LI increased gradually from group A to D. The rate of microscopic venous invasion in group B was higher than in group A (P < 0.05), in group D higher than in group B (P < 0.05), but no significant difference was observed between groups B and C, groups C and D (P = 0.16, 0.13 respectively). The rate of postoperative recurrence of HCC was higher in group B than in group A, and lower than in group C. Multivariate regression analysis: showed postoperative recurrence was correlated very well with microscopic venous invasion (r = 0.783, P < 0.01), and MVD (r = 0.143, P < 0.05). Metastasis of HCC were associated very well with PCNA-LI (r = 0.590, P < 0.01) and MVD (r = 0.179, P < 0.05), and negatively correlated with the rate of ICAM-1 expression (r = -0.183, P < 0.01).

CONCLUSIONSVEGF, uPA and ICAM-1 protein expression and proliferation of cancer cells could contribute to the formation of PVTT, metastasis and postoperative recurrence of HCC. Over-proliferated cancer cells in HCC could be the direct factor of intrahepatic metastasis and formation of PVTT, and microscopic venous invasion may be a significant factor to predict postoperative recurrence of HCC.

Carcinoma, Hepatocellular ; blood supply ; pathology ; secondary ; Endothelial Growth Factors ; analysis ; Humans ; Immunohistochemistry ; Intercellular Adhesion Molecule-1 ; analysis ; Intercellular Signaling Peptides and Proteins ; analysis ; Liver Neoplasms ; blood supply ; chemistry ; pathology ; Lymphokines ; analysis ; Neoplasm Recurrence, Local ; Proliferating Cell Nuclear Antigen ; analysis ; Urokinase-Type Plasminogen Activator ; analysis ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors