• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6639-6643
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• 2015

Background: Prostate cancer is a major concern of public health. Microvascular density (MVD) is one of the prognostic markers for various solid cancers. Matrix metalloproteinase 11 (MMP11) plays an important role in angiogenesis and changes in its expression level are known to be associated with tumor progression and clinical outcome. Aim: To investigate the relationship between MVD and MMP11 expression in prostatic adenocarcinoma tissues. Materials and Methods: The expression levels of MMP11 and MVD were analyzed immunohistochemically for 50 specimens of prostatic adenocarcinoma. Results: MMP11 was mainly expressed in stromal cells but rarely seen in epithelial cells. Mean MVD was $36/mm^2$, and it was correlated significantly only with bone metastases. MVD was also significantly correlated with MMP11 expression (r=0.29, p=0.044). Conclusions: MMP11 may alter the stromal microenvironment of prostate cancer to stimulate tumor angiogenesis.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.70-75
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• 1998

Tumor growth and metastasis depends on angiogenesis. Vascular endothelial growth factor (VEGF) is a potent mitogen for vascular endothelial cells in vitro and promotes neoangiogenesis in vivo. Objective: Follicular thyroid cancers(FTC) are a vascular tumor and traditionally metastasize via blood vessels. Likely other cancers, angiogenesis may playa important role in FTC. We, therefore, investigated the expression of VEGF and microvascular density by immunohistochemistry in FTC and follicular adenoma(FA). Materials and Methods: Findings of immunohistochemical stainings for VEGF and CD31 were measured by grading scale from +1 to 4+(strongest) and by counting the stained microvessels in 14 FTCs and 14 FAs. Results: 1) Expression of VEGF. a) FTCs have stronger expression than FAs in areas of tumor adjacent to capsule($mean{\pm}SD\:\;3.2{\pm}0.9\;vs\;2.0{\pm}0.9$, p<0.01) and in central area($2.3{\pm}0.7\;vs\;1.3{\pm}0.6$, p<0.01). b) The VEGF expression of capsular area in FTCs are higher than that of central area(p<0.05). 2) Microvascular density by CD31. a) FTCs have more microvessels than FAs in areas of adjacent to capsule($78.9{\pm}27.3\;vs\;38.7{\pm}15.6$, p<0.01) and in central area($75.5{\pm}23.3\;vs\;27.8{\pm}10.7$, p<0.01). b) In FTCs, the number of microvessels of capsular area are more than that of central tumor area, but not significant statistically(p>0.05). Conclusion: The higher expression of VEGF and microvascular density in FTC suggests angiogenesis plays an important role in progression of FTC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7513-7516
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• 2015

Background: Pyogenic granuloma is a common non-neoplastic connective tissue proliferation. ICAM-1 and VCAM-1 are vascular adhesion molecules and CD34 is a marker for evaluation of angiogenesis. The purpose of this study was to compare the immunohistochemical expression of ICAM-1, VCAM-1 & CD34 in oral pyogenic granuloma and normal gingiva. Materials and Methods: This study was performed on thirty five formalin-fixed, paraffin embedded samples of gingival pyogenic granuloma. Also we used thirty five paraffined blocks of normal gingiva as control group which were taken from crown lengthening surgery. We employed immunohistochemistry staining for our prepared microscopic slides using monoclonal mouse anti-human antibodies against ICAM-1 (CD54), VCAM-1 (CD106) and CD34. Slides were examined under light microscope and then the mean amount of stained vessels also known as microvascular density (MVD) in highly vascularized areas (hot spots) was measured. Paired t-test and repeated measures ANOVA were used to compare the difference between quantitative variables and Chi-square test for qualitative variables in different groups. Pearson correlation coefficient was used to compare relations between quantitative variables. P<0.05 was considered significant. Results: The mean of MVD for ICAM-1, VCAM-1 and CD34 was significantly higher in pyogenic granuloma than normal gingiva (p<0.001 & p<0.001 & p<0.001, respectively). Expression of CD34 in pyogenic granuloma was significantly higher than ICAM-1 and VCAM-1 (P<0.001). Besides, expression of ICAM-1 in normal gingiva, was significantly lower than two other markers (p<0.001). Conclusions: Regarding the results, it seems that ICAM-1, VCAM-1 and CD34 are useful biomarkers in evaluation of vascular and inflammatory lesions such as gingival pyogenic granuloma and the results indicate the role of these biomarkers in pathogenesis of oral pyogenic granuloma.

• Journal of Korean Neurosurgical Society
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• v.50 no.4
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• pp.281-287
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• 2011

Objective : Pituitary apoplexy is life-threatening clinical syndrome caused by the rapid enlargement of a pituitary tumor due to hemorrhage and/or infarction. The pathogenesis of pituitary apoplexy is not completely understood. We analyzed the magnetic resonance imaging (MRI) of pituitary tumors and subsequently correlated the radiological findings with the clinical presentation. Additionally, immunohistochemistry was also performed to determine whether certain biomarkers are related to radiological apoplexy. Methods : Thirty-four cases of pituitary adenoma were enrolled for retrospective analysis. In this study, the radiological apoplexy was defined as cases where hemorrhage, infarction or cysts were identified on MRI. Acute clinical presentation was defined as the presence of any of the following symptoms: severe sudden onset headache, decreased visual acuity and/or visual field deficit, and acute mental status changes. Angiogenesis was quantified by immunohistochemical expression of fetal liver kinase 1 (Flk-1), neuropilin (NRP) and vascular endothelial growth factor (VEGF) expression, while microvascular density (MVD) was assessed using Endoglin and CD31. Results : Clinically, fourteen patients presented with acute symptoms and 20 for mild or none clinical symptoms. Radiologically, fifteen patients met the criteria for radiological apoplexy. Of the fifteen patients with radiologic apoplexy, 9 patients presented acute symptoms whereas of the 19 patient without radiologic apoplexy, 5 patients presented acute symptoms. Of the five biomarkers tracked, only VEGF was found to be positively correlated with both radiological and nonradiological apoplexy. Conclusion : While pituitary apoplexy is currently defined in cases where clinical symptoms can be histologically confirmed, we contend that cases of radiologically identified pituitary hemorrhages that present with mild or no symptoms should be designated subacute or subclinical apoplexy. VEGF is believed to have a positive correlation with pituitary hemorrhage. Considering the high rate of symptomatic or asymptomatic pituitary tumor hemorrhage, additional studies are needed to detect predictors of the pituitary hemorrhage.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2277-2281
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• 2015

Objectives: To explore the expression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and analyze its correlation with microvascular density (MVD), nuclear factor kappaB (NF-kB p65) and vascular endothelial growth factor (VEGF). Materials and Methods: Immunohistochemical MaxVision method was adopted to detect the expression level of AEG-1, NF-kB p65 and VEGF in 45 samples of invading cervical cancer and 12 samples of cervicitis from The First Affiliated Hospital of Wenzhou Medical University. Tumor microvascular endothelial marker CD34 combined with Weidner was used to determine the MVD in cervical cancer tissue. The positive expression and staining conditions of AEG-1, NF-kB p65 and VEGF in cervical cancer tissues were observed under a light microscope. Correlations between expression of AEG-1 protein and those of NF-Kb p65 and VEGF, as well as MVD, were analyzed using Pearson correlation. Results: The expression levels of AEG-1 were $0.186{\pm}0.043$ in cervical cancer and $0.051{\pm}0.002$ in chronic cervicitis (p<0.01). Moreover, expression of AEG-1 was related to vascular invasion and lymphatic metastasis of cervical cancer (p<0.01), but not with age of the patients, differentiation degree, tumour size, pathological type and parametrial infiltration (p>0.05). Pearson correlation analysis showed that the expression of AEG-1 was linked with NF-kB p65 (r=0.501, p=0.000), VEGF (r=0.718, p=0.000) as well as MVD in cervical cancer tissue (r=0.815, p=0.000). Conclusions: AEG-1 is highly expressed in cervical cancer and promotes angiogenesis, which might be related to the fact that AEG-1 activating the signal pathway of NF-kB could up-regulate the level of VEGF expression.

• Journal of Life Science
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• v.26 no.12
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• pp.1367-1375
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• 2016

Cilostazol is known to be a selective inhibitor of phosphodiesterase III and is generally used to treat stroke. Our previous findings showed that cilostazol enhanced capillary density through angiogenesis after focal cerebral ischemia. Angiogenesis is an important physiological process for promoting revascularization to overcome tissue ischemia. It is a multistep process consisting of endothelial cell proliferation, migration, and tubular structure formation. Here, we examined the modulatory effect of cilostazol at each step of the angiogenic mechanism by using human brain microvascular endothelial cells (HBMECs). We found that cilostazol increased the migration of HBMECs in a dose-dependent manner. However, it did not enhance HBMEC proliferation and capillary-like tube formation. We used a cDNA microarray to analyze the mechanisms of cilostazol in cell migration. We picked five candidate genes that were potentially related to cell migration, and we confirmed the gene expression levels by real-time PCR. The genes phosphoserine aminotransferase 1 (PSAT1) and CCAAT/enhancer binding protein ${\beta}$ ($C/EBP{\beta}$) were up-regulated. The genes tissue factor pathway inhibitor 2 (TFPI2), retinoic acid receptor responder 1 (RARRES1), and RARRES3 were down-regulated. Our observations suggest that cilostazol can promote angiogenesis by promoting endothelial migration. Understanding the cilostazol-modulated regulatory mechanisms in brain endothelial cells may help stimulate blood vessel formation for the treatment of ischemic diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.29-32
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• 2014

Background and Objective: Lung cancer is one of the malignant diseases which most seriously threat humansurvival and development. This study aimed to assess osteopontin (OPN) expression in non-small cell lung cancer (NSCLC) and any relationship with clinicopathological features. Methods: Immunohistochemistry was used to determine OPN expression and microvascular density (MVD) in 120 cases of NSCLC also undergoing clinical assessment. Results: Moderately positive expression of OPN was found in 34.6% (41/120) and strong expression in 47.5% (57/120) of the NSCLCs; OPN expression in carcinomas was higher than in pericarcinoma tissues (P<0.05). While no obvious association was observed with NSCLC patient age, gender, maximum diameter of the tumor and pathological type, OPN expression was more commonly detected in poorly differentiated carcinoma tissue and lymph node metastasis as well as at advanced clinical stage (P<0.05); OPN expression in cancer tissue was positively correlated with MVD (r = 0.839, P = 0.000). Conclusion: OPN plays an important role in promoting tumor angiogenesis and progress of NSCLCs and has the possibility to become the new target for therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4453-4458
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• 2012

Angiogenesis plays a significant role in colorectal cancer (CRC) and cyclooxygenase-2 (COX-2) appears to be involved with multiple aspects of CRC angiogenesis. Our aim was to investigate the inhibitory effects of Tan II-A (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of expression of COX-2 and VEGF in CRC. We established the mice xenograft model of C26 CRC cell line, and injected 0.5, 1, 2mg/kg of Tan II-A and 1mg/kg of 5-FU in respectively in vivo. Then, we assayed tumor weight and volume, and evaluated microvascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids were transfected into HCT-116 cells, followed by detection of COX-2 promoter activity by chemiluminescence, and detection of COX-2 mRNA expression by fluorescence quantitative PCR. Taken together, the results showed Tan II-A could inhibit tumor growth and suppress the VEGF level in vivo. HCT-116 cell experiments showed marked inhibitory effects of Tan II-A on COX-2 and VEGF in a dose-dependent manner. The results indicate that Tan II-A can effectively inhibit tumor growth and angiogenesis of human colorectal cancer via inhibiting the expression level of COX-2 and VEGF.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3379-3383
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• 2012

Objective: To investigate uPA and VEGF expression in esophageal cancer and relations with tumorous invasion and metastasis. Methods: Immunohistochemistry was used to detect uPA and VEGF expression in the normal epithelial tissue of esophageal mucosa and cancer tissue and detect CD34 labeled micrangium and analyze the relationships with clinical pathological features and tumor angiogenesis. Results: Positive rates for uPA and VEGF protein expression were significantly greater in esophageal cancer than normal epithelial tissue (P < 0.05), the two being linked (P <0.05). In addition, uPA and VEGF protein expression of the high microvessel density (MVD) group was significantly lower than in the low MVD group (P < 0.05), with relation to clinical pathological staging, differentiation and lymph node metastasis (P < 0.05). Conclusion: In esophageal cancer tissue, uPA and VEGF proteins are overexpressed and promote tumor angiogenesis, indicative of a poor prognosis.

• Archives of Plastic Surgery
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• v.34 no.3
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• pp.291-297
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• 2007

Purpose: Platelet-rich plasma(PRP) contains protein growth factors, which are actively secreted by platelets to promote wound healing. However, it is not clear whether the injection of PRP into the autologous fat grafts increases the survival rate and the degree of angiogenesis. Methods: New Zealand White rabbit ears were injected fat with PRP, saline, insulin or isoproterenol (n=8/each group) for observation of the survival and degree of angiogenesis of the injected fat. The volume of the harvested fat and the degree of angiogenesis from dorsum of rabbit ears were evaluated 4, 8, and 12 weeks after the autologous fat graft. The degree of angiogenesis was measured with microvascular density (MVD) counts. Results: The volume of harvested fat decreased in a time-dependent manner after autologous fat grafts, but the decrease rate in volume of harvested fat was slower in PRP-injected group compared to that of other control groups. The difference in the volume of the harvested fat between PRP-injected group and other control groups became significant from 4 weeks after the autologous fat graft, and was maintained up to 12 weeks. However, there was no significant difference between PRP-injected group and insulin-injected group 8 and 12 weeks after the autologous fat graft. On the contrary, MVD counts increased in a time-dependent manner after autologous fat grafts. The MVD counts were significantly higher in PRP-and insulin-injected groups than in other control groups from 4 weeks after the autologous fat graft, and these differences were maintained up to 12 weeks. There was no correlation between mean platelet numbers and the volume of harvested fat. Conclusion: The present study demonstrates that PRP-injection into autologous fat grafts increases the survival rate and the degree of angiogenesis. Thus, PRP injection with autologous fat grafts would be a promising tool for maintaining the volume of the grafted fat.