• Current Optics and Photonics
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• v.3 no.1
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• pp.54-65
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• 2019

To develop a biomarker predicting tumor treatment efficacy is helpful to reduce time, medical expenditure, and efforts in oncology therapy. In clinics, microvessel density using immunohistochemistry has been proposed as an indicator that correlates with both tumor size and metastasis of cancer. In the preclinical study, we hypothesized that vascular morphometrics using optical coherence tomography angiography (OCTA) could be potential indicators to estimate the treatment efficacy of breast cancer. To verify this hypothesis, a 13762-MAT-B-III rat breast tumor was grown in a dorsal skinfold window chamber which was applied to a nude mouse, and the change in vascular morphology was longitudinally monitored during tumor growth and metronomic cyclophosphamide treatment. Based on the daily OCTA maximum intensity projection map, multiple vessel parameters (vessel skeleton density, vessel diameter index, fractal dimension, and lacunarity) were compared with the tumor size in no tumor, treated tumor, and untreated tumor cases. Although each case has only one animal, we found that the vessel skeleton density (VSD), vessel diameter index and fractal dimension (FD) tended to be positively correlated with tumor size while lacunarity showed a partially negative correlation. Moreover, we observed that the changes in the VSD and FD are prior to the morphological change of the tumor. This feasibility study would be helpful in evaluating the tumor vascular response to treatment in preclinical settings.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.36 no.3
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• pp.85-93
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• 2014

Purpose: Nodal metastasis is the main prognostic factor in the patients with oral squamous cell carcinoma (OSCC). We investigated the association between tumor-associated lymphatics and OSCC characteristics. Methods: Thirty-four specimens were used for the immunohistochemical staining with the antibody for vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, phosphorylated VEGFR-3, D2-40, and matrix metallproteinases (MMPs). We observed the distribution of the lymphangiogenic factors and quantified the degree of expression. We determined lymphatic vessel density (LVD) and lymphatic vessel dilatation with D2-40 immunostaining. We assessed the association of LVD or lymphatic vessel dilatation with tumor progression or tumor differentiation. Results: OSCC cells expressed lymphangiogenic ligands. Lymphangiogenic receptor, VEGFR-3, was expressed and activated in some tumor cells as well as in tumor-associated endothelial cells. LVD was not associated with tumor size or nodal status, but lymphatic vessel dilatation was higher in tumors with nodal metastasis, and also higher in poorly differentiated tumors. In stromal area of OSCC, MMP-1 and MMP-10 were up-regulated and the basement membrane of tumor-associated endothelial cells was destroyed by these collagenases. Conclusion: In the primary tumors with nodal metastasis, especially in poorly differentiated OSCC, tumor cells invaded the dilated lymphatic vessels via ruptured sites. MMP-1 and MMP-10 are important in the lysis of the glycocalyx inside the tumor-associated lymphatic endothelial cells.

• Korean Journal of Head & Neck Oncology
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• v.20 no.2
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• pp.128-134
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• 2004

Background and Objectives: Angiogenesis is the process of new blood vessel development from preexisting vessel. Angiogenenesis has been considered to be essential for the growth and expansion of a solid tumor. Vascular endothelial growth factor (VEGF), known as one of the most important vascular permeability factors, induces proliferation of endothelial cells, stiumulates angiogenesis, and increases vascular permeability. Several recents reports have documented that VEGF overexpression is associated with poor clinical outcomes in many maligmancies. The aims of this study were to determine whether microvessel density and VEGF expression are related to clinicopathologic factors such as age, sex, tumor size, tumor stage, and prognostic factors and to evaluate the relationship between VEGF expression and angiogenesis in benign and malignant thyroid tumors. Materials and Methods: The subjects were 65 patients (27 with papillary carcinoma, 27 with adenomatous hyperplasia, 11 with follicular adenoma) who underwent thyroidectomy from 1995 to 2001. Imuunohistochemistry was used to detect VEGF expression and microvessel density (MVD) in paraffin-embedded thryoid tumor specimens. Results: The intensity of the VEGF expression did not show stastically difference between benign and malignant thyroid tumors. There was no apparent correlation between VEGF expression and age, tumor size, T stage or scores of the AGES, AMES and MACIS systems. The neo-microvessel density was higher in the maligant tumor than the benign tumors. Also, higher neo-microvessel density was associated with metastases of the lymph nodes and scores of the AMES and AGES systems. Conclusion: Our results suggest that neo-microvessel vessel density may be a significant prognostic factor in the thyroid papillary carcinoma. But the VEGF expression does not appear to be an significant independent prognostic factor for thyroid papillary carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.583-587
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• 2013

This study aimed to investigate tumor microvessel density (MVD) and lymphatic vessel density (LVD) using the Chalkley method as predictive markers for the risk of axillary lymph node metastasis and their relationship to other clinicopathological parameters in primary breast cancer cases. Forty two node-positive and eighty node-negative breast cancers were immunostained for CD34 and D2-40. MVD and LVD were counted by the Chalkley method at x400 magnification. There was a positive significant correlation of the MVD with the tumor size, coexisting ductal carcinoma in situ (DCIS) and lymph node metastases (P<0.05). In multivariate analysis, the MVD (2.86-4: OR 5.87 95%CI 1.05-32; >4: OR 20.03 95%CI 3.47-115.55), lymphovascular invasion (OR 3.46, 95% CI 1.13-10.58), and associated DCIS (OR 3.1, 95%CI 1.04-9.23) independently predicted axillary lymph node metastasis. There was no significant relationship between LVD and axillary lymph node metastasis. However, D2-40 was a good lymphatic vessel marker to enhance the detection of lymphatic invasion compared to H and E staining. In conclusion, MVD by the Chalkley method, lymphovascular invasion and associated DCIS can be additional predictive factors for axillary lymph node metastases in breast cancer. No relationship was identified between LVD and clinicopathological variables, including axillary lymph node metastasis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.1
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• pp.1-8
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• 2010

Background and Purpose: Vascular endothelial growth factor (VEGF)-C and VEGF receptor (VEGFR)-3 are involved in tumor lymphangiogenesis. Oral mucosal squamous cell carcinoma (OMSCC) preferentially metastasizes to cervical lymph nodes, so we investigated the expression and distribution of VEGFR-3 signaling proteins in OMSCC. Materials and Methods: Tissue samples of 18 OMSCC, 10 oral mucosal leukoplakia, and 3 normal oral mucosa were evaluated for expression of VEGF-C, VEGF-D, and VEGFR-3 by immunohistochemical staining. The presence of lymphatic vessels was determined using D2-40 staining, by which we also measured lymphatic vessel density (LVD). Results: 72% (13/18) and 56% (10/18) of tissue samples showed VEGF-C and VEGF-D immunopositivity in tumor cells and tumor-associated endothelial cells. VEGFR-3 was also expressed in most of OMSCC, which was up-regulated when compared with normal mucosa or with leukoplakia. Furthermore, LVD was higher in OMSCC than in leukoplakia. Conclusion: Taken together, our results suggest that autocrine activation of lymphatic endothelial cell via VEGFR-3 by VEGF-C and/or VEGF-D could be involved in progression of OMSCC. Therefore, VEGF-C/VEGFR-3 signaling pathway can be a molecular target for anti-metastatic therapy in OMSCC.

• Korean Journal of Radiology
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• v.22 no.7
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• pp.1185-1193
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• 2021

Objective: Clear cell sarcoma of the kidney (CCSK) is the second-most common but extremely rare primary renal malignancy in children after Wilms' tumor. The aims of this study were to evaluate the imaging features that could distinguish between CCSK and Wilms' tumor and to assess the features with diagnostic value for identifying CCSK. Materials and Methods: We reviewed the initial contrast-enhanced abdominal-pelvic CT scans of children with CCSK and Wilms' tumor between 2010 to 2019. Fifty-eight children (32 males and 26 females; age, 0.3-10 years), 7 with CCSK, and 51 with Wilms' tumor, were included. The maximum tumor diameter, presence of engorged perinephric vessels, maximum density of the tumor (Tmax) of the enhancing solid portion, paraspinal muscle, contralateral renal vein density, and density ratios (Tmax/muscle and Tmax/vein) were analyzed on the renal parenchymal phase of contrast-enhanced CT. Fisher's exact tests and Mann-Whitney U tests were conducted to analyze the categorical and continuous variables, respectively. Logistic regression and receiver operating characteristic curve analyses were also performed. Results: The age, sex, and tumor diameter did not differ between the two groups. Engorged perinephric vessels were more common in patients in the CCSK group (71% [5/7] vs. 16% [8/51], p = 0.005). Tmax (median, 148.0 vs. 111.0 Hounsfield unit, p = 0.004), Tmax/muscle (median, 2.64 vs. 1.67, p = 0.002), and Tmax/vein (median, 0.94 vs. 0.59, p = 0.002) were higher in the CCSK compared to the Wilms' group. Multiple logistic regression revealed that engorged vessels (odds ratio 13.615; 95% confidence interval [CI], 1.770-104.730) and Tmax/muscle (odds ratio 5.881; 95% CI, 1.337-25.871) were significant predictors of CCSK. The cutoff values of Tmax/muscle (86% sensitivity, 77% specificity) and Tmax/vein (71% sensitivity, 86% specificity) for the diagnosis of CCSK were 1.97 and 0.76, respectively. Conclusion: Perinephric vessel engorgement and greater tumor enhancement (Tmax/muscle > 1.97 or Tmax/vein > 0.76) are helpful for differentiating between CCSK and Wilms' tumor in children aged below 10 years.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.2
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• pp.155-160
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• 2002

Oral squamous cell carcinoma (OSCC), the most common head and neck cancer, shows poor prognosis as a result of frequent local invasion and lymph node metastasis that is mediated by multiple proteolytic enzymes and angiogenesis. In recent reports, angiogenesis is known to play an important role in tumor invasion and metastasis. The purpose of this study was to determine the role of angiogenesis in OSCCs, particularly with respect to the invasive and the metastatic potential. The microvessel density (CD31) in 34 human OSCC cases were investigated by immunohistochemistry, and reviewed with respect to the invasiveness and the presence of lymph node metastasis and following results were obtained. The blood vessel density $(28.8{\pm}7.9)$ in the strong invasive cases were significantly higher than those $(23.3{\pm}6.9)$ in the weak invasive cases. (p<0.05) In the 14 cases with lymph node metastasis, the average blood vessel density was $28.5{\pm}9.6$. On the other hand, in the 20 cases without lymph node metastasis, the blood vessel density was $25.2{\pm}6.4$. The blood vessel density was not statistically related to lymph node metastasis. (p>0.05) These results suggest that angiogenesis may be related to the local invasion of OSCC and further research will be needed to investigate the possibility that antiangiogenic agent can be used as an anticancer agent for OSCC.

• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.183-189
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• 2005

Objectives: Angiogenesis is the process of new blood vessel development from preexisting vessel. The growth of tumor is dependent on angiogenesis. This study was aimed to determine the role of the VEGF expression and MVD(microvessel density) in salivary gland tumors and to analyze the correlation between the expression of VEGF/MVD, and clinical manifestation. Material and Methods: We analyzed the expression of VEGF and average MVD and neo-MVD in the 57 cases of salivary gland tumors by immunohistochemistry. Results: VEGF expression was higher in malignant tumors than in benign tumors. Average and neo-MVD were not different in benign tumor and malignant tumor. There was a tendency of positive correlation between VEGF expression and MVD but it was not statistically significant. Stage, T stage and recurrance rate were not correlated with VEGF expression, average-MVD and neo-MVD. Expression of VEGF, average-MVD and neo-MVD were significantly increased in Warthin's tumor compared with pleomorphic adenoma. Conclusion: Overexpression of VEGF has an important role in malignant salivary gland tumors.

• Journal of Korean Traditional Oncology
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• v.14 no.1
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• pp.75-84
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• 2009

Gekko has been used for several diseases including cancer in Oriental medicine and fork herbalogy. Nevertheless, its origin as herbal medicine and its efficacy and mechanism as anti-tumor drug have not yet been thoroughly reported in Korea. This study aimed to investigate anti-tumor effect of Gekko through selected articles from cqvip database in China. In vitro and In vivo, Gekko could obviously inhibit tumor growth, induce tumor cells apoptosis, reduce micro-vessel density in tumor tissue through down regulating VEGF & bFGF protein expression, promote cytotoxicity of lymphocyte. Gekko could improve survival rate, relive clinical symptoms, improve quality of life, and relieve anti-tumor treatment reaction, suggesting that Gekko might be a effective anti-tumor drug.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3079-3083
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• 2013

Objective: To investigate the effects of endostar, a recombined humanized endostatin, plus cisplatin on the growth, lymphangiogenesis and lymphatic metastasis of the Lewis lung carcinoma (LLC) in mice. Methods: A tumor model were established in C57BL/6 mice by intravenious transplantation of LLC cells. Then the mice were randomized to receive administration with NS, endostar, cisplatin, or endostar plus cisplatin. After the mice were sacrificed, tumor multiplicity, tumor size and lymph node metastasis were assessed. Then the expression of vascular endothelial growth factor-c (VEGF-C) and podoplanin were determined by immunohistochemical staining. Results: Endostar plus cisplatin significantly suppressed tumor growth. lymphatic metastasis and prolonged survival time of the mice without obvious toxicity. The inhibition of lymphatic metastasis was associated with decreased microlymphatic vessel density (MLVD) and expression of VEGF-C. Conclusions: Endostar combined with cisplatin was more effective to suppress tumor growth and lymphatic metastasis than either agent alone. Thus this may provide a rational alternative for lung carcinoma treatment.