OBJECTIVETo compare the histological morphology, hemodynamics and angiogenesis-related molecules between benign and malignant breast tumor and investigate their variation in different perfusion regions in the same type of tumors.

METHODSThirty patients with malignant breast carcinoma and 30 with breast fibroadenoma underwent contrast-enhanced ultrasound examination with time-intensity quantitative analysis. The perfusion indices including peak intensity (PI), area under the curve (AUC), time to peak (TTP) and wash-out time (WOT) were measured both inside and on the margin of the foci. The expressions of CD34, vascular endothelial growth factor (VEGF), and Flk-1/KDR in both groups were measured immuhistochemically.

RESULTSThe time-intensity curve (TIC) of malignant tumor group was characterized by rapid ascent and slow descent, while that of the benign group presented with slow ascent and rapid descent. The AUC and WOT of the malignant tumor group were significantly higher than those of the benign group, while the PI and TTP showed no significant difference. In malignant tumor group, PI, AUC and WOT on the margin of the foci were significantly higher those of the inside region, while TTP showed a reverse pattern. No significant differences were found in the perfusion parameters between the inside and outside of the foci in the benign group. The distribution of CD34 was heterogeneous in breast carcinoma, and the micro-vessels were densely distributed especially on the margin of the cancer nest. The microvessel density of the malignant group (34.48-/+8.34) was significantly higher than that of the benign group (18.65-/+4.69). Diffuse or focal high VEGF expression was found on the margin of the cancer nest and necrotic tissue, but hardly detected in the benign group. Flk-1/KDR expressed diffusely or focally in breast carcinoma with especial high expression on the margin of the cancer nest and necrotic tissue, but was virtually undetectable in the benign group.

CONCLUSIONThe perfusion pattern, TIC, mean perfusion parameter and variation of the regional perfusion parameters provide valuable evidence for differential diagnoses between benign and malignant breast tumors. Molecular imaging targeting VEGF and Flk-1/KD shed light on new approaches to early diagnosis of breast carcinoma.

Antigens, CD34 ; metabolism ; Breast Neoplasms ; blood supply ; diagnostic imaging ; metabolism ; pathology ; Fibroadenoma ; blood supply ; diagnostic imaging ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Hemodynamics ; Humans ; Immunohistochemistry ; Time Factors ; Ultrasonography ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVETo investigate the differences in the expression of angiogenesis-related molecules between benign and malignant breast neoplasms.

METHODSThirty breast cancer patients (33 foci) and 30 with benign breast neoplasms (34 foci) were examined for CD34, vascular endothelial growth factor (VEGF) and Flk-1/KDR expressions using immunohistochemistry.

RESULTSIn patients with breast cancer, the microvessels densely distributed around the cancer nest. The microvessel density (MVD) in the cancer patients was significantly higher than that in patients with benign tumors (34.48+/-8.34 vs 18.65+/-4.69, P<0.05). In the breast cancer patients, strong VEGF expression was found in the epithelial cells and vascular endothelial cells around the breast carcinoma, and Flk-1/KDR was also strongly expressed in the vascular endothelial cells. The expressions of VEGF and Flk-1/KDR were hardly detectable in the benign tumors.

CONCLUSIONVEGF is an important regulatory factor in promoting breast tumor angiogenesis.

Breast Neoplasms ; blood supply ; metabolism ; Carcinoma, Ductal, Breast ; blood supply ; metabolism ; Female ; Humans ; Neovascularization, Pathologic ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVESTo investigate the expression of CD34, vascular endothelial growth factor (VEGF) and its receptor Flk-1/KDR in precancerous lesion, atypical hyperplasia (AH) and infiltrating carcinoma of breast cancer and to explore the correlation between angiogenesis abnormality and the tumor progression.

METHODSOne hundred and sixty cases of resected tissues from breast cancer patients were enrolled in the study and were divided into 5 groups: 30 cases as normal controls, 30 cases with simple hyperplasia, 30 cases with AH, 20 cases with intraductal carcinoma in situ and 50 cases with infiltrating ductal carcinoma. The expression of CD34, VEGF and its receptor, Flk-1/KDR in those tissues were determined with immunohistochemical techniques. The micro vascular density (MVD) in those tissues was determined with the expression of CD34.

RESULTSThe expression level of CD34, VEGF and Flk-1/KDR were different among the groups, with the highest expression in the infiltrating ductal carcinoma group. With the progression of breast cancer, the major indexes showed no significant changes in the early stage of progression, but the expression of VEGF and Flk-1/KDR increased significantly from AH stage. Meanwhile, the MVD increased in the same way. There was significant difference between AH and intraductal carcinoma group in the expression of VEGF and Flk-1/KDR (P<0.05), but not in the MVD (P>0.05).

CONCLUSIONSAbnormality in angiogenesis may be an early event in the tumorigenesis of breast cancer. Abnormal expression of VEGF and Flk-1/KDR may be the initiating factor of angiogenesis in the process of breast hyperplasia-AH-breast cancer, it could be the molecular target of early diagnosis and treatment.

Adult ; Aged ; Antigens, CD34 ; metabolism ; Breast ; metabolism ; pathology ; Breast Neoplasms ; blood supply ; metabolism ; pathology ; Case-Control Studies ; Disease Progression ; Female ; Humans ; Middle Aged ; Neovascularization, Pathologic ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVETo investigate effects of exercise training on vascular regulators and discuss its antihypertensive mechanism.

METHODSRats were divided into three groups (n = 7): spontaneous hypertensive rats control group (SHR-C), training group (SHR-T) and normotensive wistar-kyoto control group (WKY-C). Aerobic exercise consisted of 10 weeks of swimming training for 5 days/week. Exercise duration was 40 min in the first week, then 50 min in the second week, from the third week to the end of training, duration was maintained at 60 min. After training, vascular endothelial growth factor (VEGF) and other biomarkers in soleus were measured by RT-PCR and immunoblotting.

RESULTSVEGF and endothelial NO synthase (eNOS) in SHR-C were lower than that in WKY-C (P < 0.05). Blood pressure in SHR-C and SHR-T were higher than that in WKY-C before training; After training, compared with SHR-C, VEGFR2, eNOS, VEGF and VEGF mRNA increased significantly in SHR-T paralleled with marked decreases in blood pressure and heart rate respectively (P < 0.05, P < 0.01).

CONCLUSIONAerobic exercise training lowered the blood pressure in spontaneous hypertensive rats, and promoted VEGF mRNA level and expressions of VEGF, VEGFR2 and eNOS. The up-regulations of these vascular regulators could benefit angiogenesis and contribute to the antihypertensive effects.

Animals ; Blood Pressure ; Hypertension ; metabolism ; therapy ; Male ; Muscle, Skeletal ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Physical Conditioning, Animal ; physiology ; Rats ; Rats, Inbred SHR ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVE: To analyze the expression of vascular endothelial growth factor (VEGF), miR-205, Ezrinand Lamin A/C in ovarian cancer tissues. METHODS: The expression of VEGF in the serum of epithelial ovarian cancer and that of healthy volunteers were detected by enzyme-linked immunosorbent assay; the expressions of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, Ezrin and Lamin A/C were detected by immunohistochemistry and the micro-vessel density (MVD) of CD31 was detected by immunohistochemistry in epithelial ovarian cancer, benign ovarian and normal ovarian specimens; and the expression of miR-205, Ezrin and Lamin A/C were detected by real-time PCR in epithelial ovarian cancer, benign ovarian and normal ovarian specimens. RESULTS: The expression of VEGF in the serum of epithelial ovarian cancer patients (116.10± 11.94) was significantly higher than that of healthy volunteers (40.04±4.97, P<0.05). The positive expression rates of VEGFR-1 and VEGFR-2 in the epithelial ovarian cancer specimens were 75.9% and 91.4% respectively, which were significantly higher than that in the benign ovarian and the normal ovarian specimens (P<0.05). No differences were observed in the positive expression rates of VEGFR-1 and VEGFR-2 between the benign ovarian and the normal ovarian specimens (P>0.05). The average length of MVD in the epithelial ovarian cancer specimens (7.56±0.51), was significantly higher than that in the normal ovarian specimens (1.22±0.56, P<0.05) and in the benign ovarian specimens (0.7±0.39, P<0.05). No differences were observed in the average length of MVD between the benign ovarian and the normal ovarian specimens (P>0.05). The relative expression level of miR-205 was 0.106±0.035 in the epithelial ovarian cancer specimens, which was significantly higher than that in the normal ovarian specimens (0.0007±0.0005, P<0.05); the relative expression level of miR-205 in the benign ovarian specimens was (0.0002±0.0002), higher than that in the normal ovarian specimens, but with no significance (P>0.05). The positive expression rates of Ezrin and Lamin A/C in the epithelial ovarian cancer specimens were 51.7% and 60.3%, respectively, which were significantly lower than those in the benign ovarian and the normal ovarian specimens (P<0.05). No differences were observed in the positive expression rates of Ezrin and Lamin A/C between the benign ovarian and the normal ovarian specimens (P>0.05). The relative expression levels of Ezrin and Lamin A/C mRNA in the epithelial ovarian cancer specimens were (0.026±0.003) and (0.060±0.007), respectively, which were significantly lower than those in the normal ovarian specimens (P<0.05). There was no statistical significance between the relative expression level of Ezrin and Lamin A/C mRNA in the epithelial ovarian cancer specimens and that in the benign ovarian specimens (0.029± 0.011, 0.089 ± 0.019; P>0.05) . CONCLUSION VEGF is significantly expressed in the serum of epithelial ovarian cancer patients; and miR-205 is up-regulated in the epithelial ovarian cancer specimens. Ezrin and Lamin A/C are down-regulated in the epithelial ovarian cancer samples. VEGF, miR-205 and target protein may be associated with the invasion and metastasis of epithelial ovarian cancer.
Carcinoma, Ovarian Epithelial ; Cytoskeletal Proteins ; genetics ; metabolism ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Lamin Type A ; genetics ; metabolism ; MicroRNAs ; genetics ; metabolism ; Neoplasms, Glandular and Epithelial ; genetics ; metabolism ; Ovarian Neoplasms ; genetics ; metabolism ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; blood ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVETo study the expression of angiotensin-2 (Ang-2), Tie-2 and vascular endothelial growth factor receptor-2 (VEGFR-2) in colorectal cancer and analyze their relationship with the occurrence, recurrence, metastasis, angiogenesis and prognosis of colorectal cancer.

METHODSImmunohistochemistry with SP method was used to detect the expressions of Ang-2, Tie-2 and VEGFR-2 in 118 colorectal cancer, 40 adjacent normal tissue and 40 benign colorectal lesion specimens.

RESULTSThe positivity rates of Ang-2, Tie-2 and VEGFR-2 in colorectal cancer tissue were 74.58%, 69.49%, and 61.02%, respectively, significantly higher than those in the adjacent normal tissues (25.00%, 17.50%, and 17.50%, P<0.05) and benign colorectal lesion tissues (35.00%, 32.50%, and 32.50%, P<0.05). The rates of two or three coexpression were significantly higher than that of a single expression in the cancer tissues (61.02% vs 15.25%). The microvascular density (MVD) of colorectal cancer tissues was 31.43∓10.50, significantly higher than that of the adjacent normal tissues (10.61∓3.76) and benign colorectal lesions (16.89∓3.83) (P<0.05). The expressions of Ang-2, Tie-2, and VEGFR-2 were positively correlated with carcinoembryonic antigen (CEA) and MVD (P<0.05). The expression of Ang-2, but not Tie-2 and VEGFR-2, was positively correlated with CA199. Ang-2, Tie-2, and VEGFR-2 expressions showed significant differences between cases with tumor recurrence/metastasis and those without 5 years after radical mastectomy, and were all positively correlated with the 5-year survival rates (P<0.05).

CONCLUSIONAng-2, Tie-2 and VEGFR-2 are involved in the development, invasion, metastasis, and prognosis of colorectal cancer, and play important roles in the angiogenesis of the tumors.

Adolescent ; Adult ; Aged ; Angiopoietin-2 ; metabolism ; Colorectal Neoplasms ; blood supply ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; metabolism ; Prognosis ; Receptor, TIE-2 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Young Adult

OBJECTIVETo conduct a preliminary study on the effect of curcumol in promoting angiogenesis activity and its mechanism in zebrafishes, in order to provide basis for clinical prescription.

METHODZebrafishes biological model was established to, observe curcumol's effect on embryo blood vessel growth, blood vessel regeneration of adult fishes after tail-cutting and tissue regeneration of fish fries after tail-cutting. The relative fluorescence quantitative PCR method was adopted to determine the gene expression of vascular endothelial growth factor (VEGFA) and receptor VEGFR2 of fish fries after tail-cutting.

RESULTCurcumol contributed to angiogenesis of intersegmental blood vessels in zebrafishes embryos and speed up regeneration of blood vessels in adult fishes after tail-cutting. Furthermore, curcumol can increase the gene expression of VEGFA and VEGFR2 in fish fries.

CONCLUSIONCurcumol can promote angiogenesis in zebrafishes, and enhance the gene expression of VEGFA and VEGFR2 in fish fries after tail-cutting and speed up the regeneration of their tails.

Animals ; Embryo, Nonmammalian ; blood supply ; drug effects ; metabolism ; Gene Expression Regulation ; drug effects ; Neovascularization, Physiologic ; drug effects ; Sesquiterpenes ; pharmacology ; Vascular Endothelial Growth Factor A ; genetics ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; Zebrafish ; embryology ; genetics ; physiology

In order to investigate the promoting effect of low-intensity treadmill exercise on rat dorsal wound healing and the mechanism, 20 Sprague-Dawley rats were randomly divided into two groups: exercise group (Ex) and non-exercise group (non-ex). The rats in Ex group were given treadmill exercise for one month, and those in non-ex group raised on the same conditions without treadmill exercise. Both groups received dorsal wound operation with free access to food and water. By two-week continuous observation and recording of the wound area, the healing rate was analyzed. The blood sample was collected at day 14 post-operation via cardiac puncture for determination of the number of endothelial progenitor cells (EPCs) by flow cytometry, and the concentrations of relevant cytokines such as basic fibroblast growth factor (bFGF), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were measured by ELISA. The skin tissue around the wound was dissected to observe the vascular density under the microscope after HE staining, to detect the mRNA level of VEGFR2 and angiopoietin-1 (Ang-1) receptor using RT-qPCR, and protein expression of a-smooth muscle actin (αSMA) and type III collagen (ColIII) using Western blotting. It was found that the wound area in Ex group was smaller at the same time point than in non-ex group. The number of circulating EPCs was greater and the concentrations of vasoactive factors such as VEGF, eNOS and bFGF were higher in Ex group than in non-ex group. HE staining displayed a higher vessel density in Ex group than in non-ex group. Moreover, the mRNA expression of VEGFR2 and Ang-1 detected in the wound tissue in Ex group was higher than in non-ex group. Meanwhile, the protein expression of αSMA and ColIII was more abundant in Ex group than in non-ex group. Conclusively, the above results demonstrate Ex rats had a higher wound healing rate, suggesting low-intensity treadmill exercise accelerates wound healing. The present work may provide some hint for future study of treating refractory wound.
Actins ; metabolism ; Animals ; Collagen Type III ; metabolism ; Cytokines ; blood ; Endothelial Progenitor Cells ; cytology ; Male ; Nitric Oxide Synthase Type III ; blood ; Physical Exertion ; RNA, Messenger ; blood ; Rats ; Rats, Sprague-Dawley ; Receptor, TIE-1 ; metabolism ; Running ; Vascular Endothelial Growth Factor A ; blood ; Vascular Endothelial Growth Factor Receptor-2 ; blood ; Wound Healing

OBJECTIVETo verify whether the extracellular domain of kinase domain region (KDR) has anti-angiogenesis activity in vivo.

METHODScDNA was cloned into adeno-associated virus (AAV) vector pSNAV and transfected to baby hamster kidney (BHK) cells. Recombinant AAV was obtained from the cell culture supernatant after adding helper virus. Recombinant AAV-infected human bladder cancer EJ cell line (EJ cells) were injected subcutaneously into Balb-c nude mice. Tumor specimens were removed from the mice, paraffin-embedded and sliced, then stained by immunohistochemistry. Microvessel density (MVD) was determined under a microscope.

RESULTSThe tumor volume developed by EJ cells transfected with the extracellular domain of KDR was significantly smaller (1.70 +/- 0.18 cm(3)) compared with that in the control (5.62 +/- 0.67 cm(3)) (P < 0.05), although tumor developed to be detectable on almost the same time (14.7 +/- 2.4 days vs 14.1 +/- 3.2 days). Further, MVD in the experimental group was lower than that in the control (41.3 +/- 4.8 vs 6.2 +/- 2.1, P < 0.05).

CONCLUSIONThe extracellular domain of KDR could be expressed in nude mouse bladder cancer tissue and inhibit tumor angiogenesis.

Animals ; Cloning, Molecular ; Cricetinae ; Dependovirus ; genetics ; Endothelial Growth Factors ; metabolism ; Female ; Genetic Therapy ; Intercellular Signaling Peptides and Proteins ; metabolism ; Lymphokines ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neovascularization, Pathologic ; prevention & control ; Urinary Bladder Neoplasms ; blood supply ; therapy ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; Vascular Endothelial Growth Factors

OBJECTIVETo investigate the association of C-erb B-2 expression with angiogenesis in nasopharygeal carcinoma.

METHODSSeventy-seven specimens of nasopharygeal carcinoma were examined immunohistochemically for protein expressions of C-erb B-2 and vascular endothelial growth factor (VEGF), and the microvessel density (MVD) was determined by immunostaining of the endothelial cells for factor VIII-related antigen (F8).

RESULTSPositive C-erb B-2 immunostaining was observed in 36.36% (28/77) of the nasopharygeal carcinoma tissues, which had a VEGF positivity rate of 32.48% (25/77). High positivity rate of C-erg B-2 was associated with high positivity rate of VEGF and high MVD (P<0.05).

CONCLUSIONThe expression of C-erb B-2 may contribute to angiogenesis in nasopharygeal carcinoma.

Adult ; Aged ; Carcinoma ; blood supply ; genetics ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; blood supply ; genetics ; metabolism ; pathology ; Neovascularization, Pathologic ; Receptor, ErbB-2 ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Young Adult