• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6397-6401
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• 2012

Background: No factor has thus far been identified to predict the efficacy of bevacizumab therapy for colorectal cancer. We here therefore studied PTEN, VEGF, HER2 and p53 by immunohistochemistry as possible prognostic and predictive factors. Materials and Methods: A total of 34 retrospectively collected tumor samples were evaluated, all from patients receiving bevacizumab-based regimens. VEGF-A, PTEN, HER2, p53 were assessed and data was compared with clinicopathologic characteristics of patients and the bevacizumab response rate. Results: In this study, the median age of the 34 metastatic colorectal cancer patients was 55.5 (24-75), twelve (35.3%) being women and 22 (64.7%) men. PTEN, VEGF, HER2, p53 expressions were compared with bevacizumab response and other chacteristics of disease. Statistical significant differences were not found between bevacizumab response rates and different expression levels of VEGF, PTEN, HER2 and p53 (respectively p=0.256, p=0.832, p=0.189, p=0.131). However, a survival difference was noted in the VEGF expression negative group (median OS:55 months; 95%CI, 22-88 months) (p=0.01). There was no statistically significant OS difference in other groups (PTEN p=0.6, HER2 p=0.189, p53 p=0.13). Conclusions: We did not find any predictive factor for BV therapy in our study. VEGF negative expression could be an important prognostic factor in metastatic colorectal carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6357-6362
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• 2012

Background: To determine the prevalence of mammalian target of rapamycin phosphorylation (p-mTOR) and vascular endothelial growth factor (VEGF) and any correlation with clinical characteristics and prognosis in ovarian clear cell carcinoma patients. Materials and Method: Seventy four paraffin-embedded specimens of such carcinomas frompatients who underwent surgery, received adjuvant chemotherapy and were followed up at King Chulalongkorn Memorial Hospital during January 2002 to December 2008 were stained with rabbit monoclonal IgG p-mTOR and rabbit polyclonal IgG VEGF using immunohistochemical methods. Medical records were reviewed and clinical variables were analysed. Results: The prevalence of positive p-mTOR in ovarian clear cell carcinoma was 87.9% and significantly higher in advance-stage than early-stage patients (100% versus 83.6%, P<0.05). Two-year disease free survival and 2-year overall survival in patients with positive p-mTOR expression were 60% and 69.2% with no differences from patients with negative p-mTOR expression (p>0.05). The prevalence of VEGF expression was 63.5% and significantly higher in chemo-sensitive than chemo-resistant patients (70.7% versus 37.5%, P<0.05). Two-year disease free survival and 2-year overall survival in patients with VEGF expression were 72.3% and 83% respectively which were significantly different from patients with negative VEGF expression (p<0.05). Conclusions: p-mTOR expression in ovarian clear cell carcinoma was significantly correlated with the stage of disease. VEGF expression was significantly correlated with chemosensitivity, and survival. Further studies of related targeted therapy might be promising.

• Journal of Gastric Cancer
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• v.6 no.4
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• pp.284-290
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• 2006

Purpose: Many previous studies have suggested that cyclooxygenase-2 (COX-2) over expression is closely related to angiogenesis. However, few have reported the relationship between COX-2 and lymphangiogenesis which is still unclear, The aim of this study was to determine the relationship between COX-2 expression and lymphangiogenetic factor, VEGF-C, in human gastric cancer and to correlate COX-2 and VEGF-C expression with other clinocopathological features to investigate whether COX-2 contributes to lymphangiogenesis and enhances lymph node metastasis. Materials and Methods: One hundred patients who underwent curative radical surgery in Hanyang University hospital from July 1998 to June 2001 were selected. The expression of COX-2 and VEGF-C were detected by using immunohistochemistry, and the relationships between these two parameters and several clinicopathological factors (gender, stage, lymph node status, tumor location, Lauren classification and angioinvasion) were determined. Results: Increased COX-2 expression was found in 86 of 100 tumor samples (86%) and in 70 of 100 tumor samples (70%) with VEGF-C. A high correlation between VEGF-C expression and lymph node metastasis was observed (P=0.033) along as well as COX-2 expression (P=0.012). Also, there was a significant correlation between COX-2 and VEGF-C expression (P=0.026), yet no correlation were found between COX-2 and VEGF-C expression and other clinicopathological parameters. Conclusion: Our study suggests that COX-2 expression contributes to lymphangiogenesis by mediating VEGF-C and finally promoting lymph node metastasis.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.68 no.1
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• pp.22-28
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• 2010

Background: Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis. VEGF production is regulated by HIF-$1{\alpha}$ and EGFR. This study examined the relationship between the clinicopathological factors and VEGF, HIF-$1{\alpha}$ and EGFR protein overexpression, and evaluated their prognostic value in patients with a surgically resected non-small cell lung cancer (NSCLC). Methods: Patients who underwent a surgical resection at Kangnam St. Mary's hospital were reviewed retrospectively. The core biopsy samples from 54 patients with NSCLC were assembled on a tissue microarray (TMA), and immunohistochemical staining for the VEGF, HIF-$1{\alpha}$ and EGFR proteins was performed. The overexpression of these proteins was evaluated in relation to age, gender, histology and staging by univariate analysis. The clinicopathological prognostic factors were analyzed. Results: Multivariate analysis performed by Cox regression (odds ratio 2.8, 95% CI 1.0~8.2, p=0.046) revealed HIF-$1{\alpha}$ overexpression to be an unfavorable factor. There was no correlation between the overexpression of these proteins and the clinicopathological factors. VEGF showed a positive relationship with EGFR, but there was no statistical significance [$p(x^2)=0.06$]. Conclusion: HIF-$1{\alpha}$ overexpression predicts shorter survival in patients with a surgically resected NSCLC. Therefore, HIF-$1{\alpha}$ may be a poor prognostic factor in NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.429-433
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• 2013

Objectives: To explore the correlation between multi-slice spiral CT (MSCT) perfusion parameters and the expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-2 (MMP-2) in breast cancer. Methods: Forty five breast cancer patients and 16 patients with benign breast tumor, both confirmed by pathology examination, were enrolled. All underwent MSCT perfusion imaging to obtain perfusion maps and data for parameters including blood flow (BF), blood volume (BV) and permeability surface (PS). Cancer patients did not receive treatment prior to surgery. The expression of VEGF and MMP-2 were examined with both immunohistochemistry and Western blotting. Results: The levels of VEGF and MMP-2 by immunohistochemistry were significantly higher in the breast cancer group (P < 0.01) than the benign tumor group. Relative OD values from Western blotting were also higher in cancer cases (P < 0.05). Similarly, the mean MSCT perfusion parameters (BF, BV, PS) were significantly higher in the breast cancer group (P < 0.01), BF and BV positively correlating with VEGF expression (r = 0.878 and 0.809 respectively, P < 0.01); PS and VEGF and MMP-2 expression were also positively correlated (r= 0.860, 0.786 respectively, P < 0.01). Conclusion: There is a correlation between breast cancer MSCT perfusion parameters and VEGF andMMP-2 expression, which might be useful for detection of breast lesions, qualitative diagnosis of breast cancer, and evaluation of breast cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3967-3971
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• 2012

Aims: To explore the relationship between various molecular makers and liver metastasis of colorectal cancer (CRC). Method: Using immunohistochemistry, protein expression of CEA, nm23, c-met, MMP2, COX-2, VEGF, EGFR, and CD44 was assessed in 80 CRC cases. The Chi-square test and logistic regression were performed to analyze the relationship between these indicators and CRC liver metastasis. Results: There were significant differences in expression of CEA, MMP2, CD44, VEGF and EGFR between the liver metastasis and non metastasis groups (P < 0.05); no significant differences were noted for nm23, c-met, and COX-2 expression. Logistic regression analysis showed that only CEA, VEGF, and EGFR entered into the regression equation, and had significant correlations with CRC liver metastasis (${\alpha}$ inclusion= 0.10, ${\alpha}$ elimination = 0.15, R2 = 0.718). Conclusions: Combination detection of CEA, VEGF, and EGFR may be an effective means to predict CRC liver metastasis. Nm23, c-met, MMP2, COX-2, and CD44, in contrast, are not suitable as prognostic markers.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.43-50
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• 2007

Background: Mutated or deregulated expression of C-erbB-2 causes this gene to function as a potent oncogene. Vascular endothelial growth factor (VEGF) is a crucial angiogenic molecule in lung cancer. Both C-erbB-2 and VEGF can promote growth, proliferation and metastasis in non-small cell lung cancer (NSCLC). The purpose of this study was to investigate evaluate the relationship between the expressions of the C-erbB-2 and VEGF genes using immunohistochemistry. Materials and Methods: Ninety-five patients with NSCLC were involved (60 squamous cell carcinoma and 35 adenocarcinoma). The formalin-fixed paraffin embedded specimens were immunohistochemically stained for C-erbB-2 and VEGF using the avidin-biotin complex method. Results: Positive C-erbB-2 expression was observed more often in adenocarcinomas than squamous cell carcinomas (p<0.05). Although the immunohistochemical expressions of C-erbB-2 and VEGF in non-small-cell lung cancer showed increased tendencies at an advanced stage, the correlation between early and advanced cancers was insignificant. In adenocarcinomas, the expressions of VEGF and C-erbB-2 were significantly (p<0.05). Conclusion: The overexpression fo C-erbB-2 was significantly higher in adenocarcinomas than squamous cell carcinomas, and correlated with the expression of VEGF in adenocarcinomas of the lungs.

• Physical Therapy Korea
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• v.13 no.2
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• pp.9-15
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• 2006

Skeletal muscle injury occurs frequently in sports medicine and is the most general form of injury followed by physical impact. There are growth factors which conduct proliferation, differentiation, and synthesis of myogenic prodromal cells and regulate vascular generation for the continued survival of myocytes. The purpose of the present study was to confirm the effects of electroacupuncture (EA) and electrical stimulation (ES) on muscle recovery processes according to vascular endothelial growth factor (VEGF) expression. Eighteen Sprague-Dawley rats were separated into 2 experimental groups and a controlled group. All animals had suffered from crush damage in the extensor digitorum longus for 30 seconds and were killed 1, 3, and 7 days after injury. 30 Hz and 1 mA impulsion for 15 minutes was applied to the EA experimental groups Zusanli (ST36) and Taichong (LR3) using electroacupuncture and the same stimulation was applied to the ES group using an electrical node. Hematoxyline-Eosin staining and VEGF immunohistochemistry were used to ascertain the resulting muscle recovery. There were few morphological differences between the EA and ES groups, and both groups were observed to have tendencies to decrease atrophy as time passed. In the controlled group, gradually diminishing atrophy could be observed, but their forms were mostly disheveled. There were few differences in VEGF expression between the EA and ES groups, and tendencies to have an increased quantity of VEGF with the lapse of time were observed in both groups. In the controlled group, a little VEGF expression could be observed merely 7 days after injury. In conclusion, EA and ES contributed to muscle recovery processes and could be used for the treatment of muscle injury.

• 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.