• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.737-741
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• 2014

Background: In recent years a wide variety of flavonoids or polyphenolic substances have been reported to possess substantial anti-carcinogenic and antimutagenic activities. Grape proanthocyanidins (GPC) are considered as good examples for which there is evidence of potential roles as anti-carcinogenic agents. Methods: A xenograft model was established using H22 cells subcutaneously injected into mice and used to assess different concentrations of grape proanthocyanidins (GPC) and Endostar. Treatments were maintained for 10 days, then levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were examined by immunohistochemistry, while VEGF mRNA was determined by real-time PCR in tumor tissue. Results: The expression of MVD and VEGF decreased gradually as the concentration of GPC increased.There was a significant positive correlation between MVD and VEGF. Conclusions: These results suggest that GPC restrains the growth of tumor, possibly by inhibiting tumour angiogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.627-633
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• 2015

Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and Methods: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. Results: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. Conclusions: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.

• Archives of Plastic Surgery
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• v.42 no.2
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• pp.150-158
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• 2015

Background Fat is widely used in soft tissue augmentation. Nevertheless, it has an unpredictably high resorption rate. Clinically, external expansion with negative pressure is used to increase fat graft survival. In this study, fat graft recipient sites were preconditioned by external application of negative pressure in order to test for improvements in vascularity and fat graft survival. Methods Negative pressure was applied randomly to either the left or right dorsal ear of 20 New Zealand male white rabbits at a pressure of -125 mm Hg. The negative pressure was removed one week after the skin perfusion was measured. The skin flap at each ear was elevated, and 1 g of fat was grafted above the dorsal perichondrium. After one week, the fat weight, microvessel density, mature vessel density of the skin and fat, and amount of glycerol released were measured. Three months after the grafting, the same measurements were performed, with the exception of glycerol release. Results The fat survival rate of the experimental group ($75.4%{\pm}3.9%$) was higher than that of the control group ($53.1%{\pm}4.3%$) (P<0.001). Skin perfusion was higher in the experimental group. The glycerol release in the experimental group was significantly higher than in the control. The microvessel density of the skin and fat was significantly higher in the experimental group. Three months after the grafting, the skin and fat mature vessel density was significantly higher in the experimental groups. Conclusions Negative pressure prior to fat grafting increased the vascularity of the recipient site, and, accordingly, enhanced fat graft survival.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4549-4552
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• 2013

The incidence of gastric cancer worldwide, and in particular in developing countries, has shown a marked increase. Poor prognosis of gastric cancer patients occurs due to the rapid metastasis of the disease via the lymphatic and blood vessels. The aim of this study was to investigate the expression and the clinical significance of D2-40 and CD34 in human gastric cancer. D2-40 and CD34 expression wasdetected in 1,072 cases of Chinese patients with gastric carcinoma using immunohistochemistry. The lymphatic vessel density (LVD) and microvessel density (MVD) were calculated and analyzed and the correlation with the clinicopathological factors and prognosis was determined. The LVD and MVD of the gastric cancer cases were significantly higher compared to those of normal tissues (P < 0.05). The expression of D2-40-LVD and CD34-MVD in the malignancies were positively related to the age, tumor size, invasion depth, lymphatic metastasis and pathological tumor-node-metastasis (pTNM) (P < 0.05); However, no statistically significant difference was identified between them with the patient gender (P > 0.05). Up-regulation of D2-40 and CD34 expression was significantly correlated with the poor survival rate in univariate and multivariate analyses. The LVD marked by D2-40 and the MVD marked by CD34 were positively correlated to the clinicopathological factors of the malignancies and may play important role in the development and progression of gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4823-4826
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• 2012

Objective: To explore serum angiogenic factor expression in patients with osteosarcoma and its relationship with metastasis. Methods: Immunohistochemistry was used to test the expression of CD34 and FVIII-Rag in osteosarcoma tissues of 36 patients (osteosarcoma group) and microvessel density (MVD) was also recorded. In addition, ELISA was used to test the level of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-${\beta}1$ (TGF-${\beta}1$) and endostatin (ES) in the osteosarcoma group and in a control group. Results: VEGF and ES level were significantly higher than in the control group before operation (P<0.01), VEGF, bFGF and TGF-${\beta}1$ correlating with the ES level (P<0.01). Serum VEGF and ES levels of osteosarcoma patients before surgery were closely related to relapse and metastasis; moreover, serum VEGF increased with MVD (P<0.01). Postoperative VEGF and ES levels were lower than the preoperation values (P<0.01); ES level in relapse group was significantly higher than that of the non-relapse group (P<0.01). Conclusion: Preoperative serum VEGF and postoperative ES levels have great predictive value with regard to relapse of osteosarcoma patients.

• Archives of Plastic Surgery
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• v.41 no.6
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• pp.647-653
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• 2014

Background Administration of growth factors has been associated with increased viability of composite grafts greater than 1-cm in diameter. Platelet-rich plasma (PRP) contains many of the growth factors studied. In this study, we evaluate the effect of PRP injection on composite graft viability and the proper time for injection. Methods A total of 24 New Zealand White rabbits were divided into four groups. Autologous PRP was injected into the recipient sites three days before grafting in group 1, on the day of grafting in group 2, and three days after grafting in group 3. Group 4 served as control without PRP administration. Auricular composite grafts of 3-cm diameter were harvested and grafted back into place after being rotated 180 degrees. Median graft viability and microvessel density were evaluated at day 21 of graft via macroscopic photographs and immunofluorescent staining, respectively. Results The median graft survival rate was 97.8% in group 1, 69.2% in group 2, 55.7% in group 3, and 40.8% in the control group. The median vessel counts were 34 (per ${\times}200$ HPF) in group 1, 24.5 in group 2, 19.5 in group 3, and 10.5 in the control group. Conclusions This study demonstrates that PRP administration is associated with increased composite graft viability. All experimental groups showed a significantly higher survival rate and microvessel density, compared with the control group. Pre-administration of PRP was followed by the highest graft survival rate and revascularization. PRP treatments are minimally invasive, fast, easily applicable, and inexpensive, and offer a potential clinical pathway to larger composite grafts.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.4
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• pp.330-336
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• 2001

Angiogenesis is an essential process for the growth, invasion and metastasis of cancer. However, it is uncertain that antiangiogenic effects can be a major treatment strategy of oral cancer. The aim of this study was to investigate whether thalidomide, which is known to be a potent inhibitor of angiogenesis, have inhibitory effect on the growth and antiangiogenic effects of oral squamous cell carcinoma(OSCC) xenografted in nude mice and whether antiangiogenesis of thalidomide can be included as a major treatment strategy of oral cancer. After human oral squamous cell carcinoma strain KB was subcutaneously implanted in 20 nude mice, the volume of tumor was measured every three days. When the tumor mass reached $75{\sim}100mm^3$, thalidomide(200mg/kg/d) was administered into 10 experimental nude mice and the same volume of distilled water was administered into 10 control nude mice and the tumor volume was measured every three days. The excised tumor masses on the 30th day after administration were frozen and processed for immunohistochemistry using vascular endothelial growth factor(VEGF) and CD31. We evaluated microvessel density and VEGF expression. The results were as follows ; 1. Thalidomide retarded the growth of human OSCC as compared with the control group, but it was not statistically significant. 2. A statistically significant lower microvessel density was observed in the thalidomide-treated group than in the control group(p<0.01) and thalidomide significantly reduced VEGF expression (p<0.01). Thalidomide exhibited significantly antiangiogenic effect, but did not inhibit the growth of human OSCC effectively. Antiangiogenic therapy of thalidomide alone is not likely to be effective in the treatment of human OSCC, but might be regarded as adjuvant chemotherapeutic strategy.

• Archives of Plastic Surgery
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• v.45 no.6
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• pp.504-511
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• 2018

Background Acellular dermal matrix (ADM) helps wound healing by stimulating angiogenesis, acting as a chemoattractant for endothelial cells, providing growth factors, and permitting a substrate for fibroblasts to attach. The current standard for using paste-type ADM (CG Paste) in wound healing is direct application over the wounds. The major concerns regarding this method are unpredictable separation from the wounds and absorption into negative-pressure wound therapy devices. This study aimed to investigate the effects of subcutaneous injection of paste-type ADM on wound healing in rats. Methods Full-thickness skin defects were created on the dorsal skin of rats. Eighteen rats were randomly divided into three groups and treated using different wound coverage methods: group A, with a saline dressing; group B, standard application of CG Paste; and group C, injection of CG Paste. On postoperative days 3, 5, 7, 10, and 14, the wound areas were analyzed morphologically. Histological and immunohistochemical tissue analyses were performed on postoperative days 3 and 7. Results Groups B and C had significantly less raw surface than group A on postoperative days 10 and 14. Collagen fiber deposition and microvessel density were significantly higher in group C than in groups A and B on postoperative days 3 and 7. Conclusions This study showed comparable effectiveness between subcutaneous injection and the conventional dressing method of paste-type ADM. Moreover, the injection of CG Paste led to improved wound healing quality through the accumulation of collagen fibers and an increase in microvessel density.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2313-2316
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• 2015

Objective: To investigate the correlation between extracellular matrix protein-1 (ECM1) and the growth, metastasis and angiogenesis of laryngeal carcinoma. Materials and Methods: Forty-five samples with laryngeal benign and malignant tumors confirmed by pathology in Laiwu City People's Hospital from March 2006 to March 2011 were collected, in which there were 29 cases with laryngeal carcinoma and 16 with benign tumors. The expression of ECM1 and factor VIII-related antigens in patients with laryngeal carcinoma and those with benign tumors was respectively detected using immunohistochemical method, and the correlation between ECM1 staining grade and microvessel density (MVD) was analyzed. Results: In laryngeal carcinoma tissue, ECM1 was mainly expressed in cytoplasm, less in cytomembrane or intercellular substance. With abundant expression in the tissue of laryngeal benign tumors (benign mesenchymoma and hemangioma), ECM1 was primarily expressed in the connective tissue, which was different from the expression in laryngeal carcinoma tissue. The proportion of positive ECM1 staining (++) in patients with laryngeal carcinoma was dramatically higher than those with benign tumors (p<0.05), and that of strongly-positive ECM1 staining (+++) slightly higher. The results of Spearman nonparametric correlation analysis revealed that ECM1 staining grade in laryngeal carcinoma tissue had a significantly-positive correlation with MVD (r=0.866, p=0.000). Conclusions: ECM1 expression in laryngeal carcinoma is closely associated with tumor cell growth, metastasis and angiogenesis, which can be considered as an effective predictor in the occurrence and postoperative recurrence of laryngeal carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2491-2494
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• 2014

Objective: To explore the mechanism and significance of tumor angiogenesis by observing changes of microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in residual tumor tissues after cryoablation. Materials and Methods: A total of 18 nude mice xenograft models with transplanted lung adenocarcinoma cell line A549 were established and randomly divided into 3 groups when the maximum diameter of tumor reached 1 cm: control, cisplatin (DDP) and cryoablation. The nude mice were sacrificed after 21-d cryoablation to obtain the tumor tissues. Then immunohistochemistry was applied to determine MVD and the expression of VEGF in tumor tissues. Results: The tumor volumes of control group, DDP group and cryoablation group were $1.48{\pm}0.14cm^3$, $1.03{\pm}0.12cm^3$ and $0.99{\pm}0.06cm^3$ respectively and the differences were significant (P<0.01), whereas MVD values were $21.1{\pm}0.86$, $24.7{\pm}0.72$ and $29.2{\pm}0.96$ (P<0.01) and the positive expression rates of VEGF were $36.2{\pm}1.72%$, $39.0{\pm}1.79%$ and $50.8{\pm}2.14%$ (P<0.01), respectively, showing that MVD was proportional to the positive expression of VEGF (r=0.928, P<0.01). Conclusions: Cryoablation can effectively inhibit tumor growth, but tumor angiogenesis significantly increases in residual tumors, with high expression of VEGF playing an important role in the residual tumor angiogenesis.