• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4445-4452
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• 2012

Background: Prognosis of breast cancer depends on classic pathological factors and also tumor angiogenesis. This study aimed to evaluate the clinicopathological factors of breast cancer in a tertiary centre with a focus on the relationship between tumor angiogenesis and clinicopathological factors. Methods: Clinicopathological data were retrieved from the archived formal pathology reports for surgical specimens diagnosed as invasive ductal carcinoma, NOS. Microvessels were immunohistochemically stained with anti-CD34 antibody and quantified as microvessel density. Results: At least 50% of 94 cases of invasive breast ductal carcinoma in the study were advanced stage. The majority had poor prognosis factors such as tumor size larger than 50mm (48.9%), positive lymph node metastasis (60.6%), and tumor grade III (52.1%). Higher percentages of estrogen and progesterone receptor negative cases were recorded (46.8% and 46.8% respectively). Her-2 overexpression cases and triple negative breast cancers constituted 24.5% and 22.3% respectively. Significantly higher microvessel density was observed in the younger patient age group (p=0.012). There were no significant associations between microvessel density and other clinicopathological factors (p>0.05). Conclusions: Majority of the breast cancer patients of this institution had advanced stage disease with poorer prognostic factors as compared to other local and western studies. Breast cancer in younger patients might be more proangiogenic.

• Journal of Korean Neurosurgical Society
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• v.58 no.5
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• pp.426-431
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• 2015

Objective : The purpose of this study was to evaluate the clinical efficacy of continuous low-dose temozolomide (TMZ) chemotherapy for recurrent and TMZ-refractory glioblastoma multiforme (GBM) and to study the relationship between its efficacy and microvessel density within the tumor. Methods : Thirty patients who had recurrent GBM following Stupp's regimen received TMZ daily at $50mg/m^2/day$ until tumor progression between 2007 and 2013. The median duration of continuous low-dose TMZ administration was 8 weeks (range, 2-64). Results : The median progression-free survival (PFS) of continuous low-dose TMZ therapy was 2 months (range, 0.5-16). At 6 months, PFS was 20%. The median overall survival (OS) from the start of this therapy to death was 6 months (95% CI : 5.1-6.9). Microvessel density of recurrent tumor tissues obtained by reoperation of 17 patients was $22.7{\pm}24.1/mm^2$ (mean${\pm}$standard deviation), and this was lower than that of the initial tumor ($61.4{\pm}32.7/mm^2$) (p-value=0.001). It suggests that standard TMZ-chemoradiotherapy reduces the microvessel density within GBM and that recurrences develop in tumor cells with low metabolic burden. The efficacy of continuous low-dose TMZ could not be expected in recurrent GBM cells in poor angiogenic environments. Conclusion : The efficacy of continuous low-dose TMZ chemotherapy is marginal. This study suggests the need to develop further treatment strategies for recurrent and TMZ-refractory GBM.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.869-874
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• 2015

Background: The prognostic value of microvessel density (MVD), reflecting angiogenesis, detected in ovarian cancer is currently controversial. Here we performed a meta-analysis of all relevant eligible studies. Materials and Methods: A comprehensive search of online PubMed, Medline, EMBASE and Sciencedirect was performed to identify all related articles. The search strategy was designed as 'microvessel density', 'ovarian cancer', 'ovarian neoplasm', 'CD34' and 'angiogenesis'. Results: The studies were categorized by author/year, number of patients, FIGO stage, histology, cutoff value for microvessel density, types of survival analysis, methods of hazard rations (HR) estimation, HR and its 95% confidence interval (CI). Combined hazard ratios suggested that high MVD was associated with poor overall survival (OS) and progression-free survival (PFS), with HR and 95% CIs of 1.84 (1.33-2.35) and 1.36 (1.06-1.66), respectively. Subgroup analysis showed that high MVD detected by CD34 was relevant for OS [HR=1.67 (1.36-2.35)], but not MVD detected with other antibodies [HR=2.11 (0.90-3.31)]. Another subgroup analysis indicated that high MVD in patients without pre-chemotherapy, but not with pre-chemotherapy, was associated with OS [HR=1.88(1.59-2.18 and HR=1.70 (-0.18-3.59)]. Conclusions: The OS and PFS with high MVD were significant poorer than with low MVD in ovarian cancer patients. However, high MVD detected by CD34 seems to be more associated with survival for patients without pre-chemotherapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.3
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• pp.209-215
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• 2006

Preoperative neoadjuvant chemotherapy using cisplatin and 5-FU is generally given in oral and maxillofacial cancer. At tissue level both inflammation and fibrosis occur after chemotherapy. The cellular changes mimic those of a granulating wound, with activated macrophages and fibroblasts replacing the malignant cells as they are erradicated. Stromal cells, together with extracellular matrix components, provide the microenvironment that is pivotal for tumor cell growth, invasion, and metastatic progression. Vascular endothelial growth factor(VEGF), an important regulator of angiogenesis in cancer, induces mitogenesis of vascular endothelial cells, and vascular permeabilization and microvessel formation in a tumor are associated with tumor nutrition and oxygenation. Also, they are associated with chemotherapeutic drug delivery. Oxygen delivery to tumor appears to rely on a network of microvessels, On the other hand, the tumor microvessel is clearly an important factor in chemotherapeutic drug delivery to cancer cells, and the efficacy of drug delivery can be high in richly vascularized tumors. So, this study was conducted to evaluate the effect of neoadjuvant chemotherapy on microvessel density from 11 patients with tongue cancers. Our results showed that neoadjuvant chemotherapy was seemed to decrease VEGF expression in tumor cells, however, it did not significantly alter VEGF expression in tumor-associated macrophages. Also, Neoadjuvant chemotherapy had little effect on the microvessel density using CD34, and tumor-associated macrophage level using CD68. Thus, tumorassociated macrophages seem to be the key factor associated with the maintenance of microvessel density after neoadjuvant chemotherapy in tongue cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2559-2564
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• 2016

Purpose: To compare Ki-67 index and microvessel density MVD) in multiple myeloma and non-myeloma patients and their correlation with each other and other prognostic markers. Materials and Methods: Forty patients were enrolled in this study between 2011-2013, 30 with multiple myelomas and 10 with non-malignant disease as controls. Proliferative activity was analyzed by Ki-67 and microvessel density (MVC) was assessed by CD34 and compared between two groups. In myeloma patients, correlation between Ki-67, MVD and other prognostic factors was assessed by Pearson correlation coefficient. Results: According to Durie Salmon staging criteria, 13 patients were of stage 1, 5 of stage II and 12 of stage III. Ki-67 expression showed a positive correlation with MVD (r=0.729, p<0.001) and was significantly higher (p<0.0001) in myeloma patients (range 35-80%, mean 60.1 %) as compared to controls (range 8-25%, mean 18.1%). $MVD/mm^2$ was also significantly (p<0.0001) higher in myeloma patients (range $62-237/mm^2$, mean $178.0/mm^2$) than controls (range $5.2-50/mm^2$, mean $18.3/mm^2$). Ki-67 and MVD, both increased progressively with increasing stage of myeloma. Ki-67 showed significant positive correlation with blood urea and lactate dehydrogenase and a significant negative correlation with serum albumin. MVD showed a significant positive correlation with blood urea, lactate dehydrogenase, serum creatinine, ${\beta}2$ microglobulin and skeletal lesions. Conclusions: Ki-67 and MVD are indicators of aggressiveness and poor prognosis having significant correlation with each other and other prognostic markers of multiple myeloma. Routine assessment of these markers may help to identify high risk patients, who may benefit from with more aggressive therapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.6
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• pp.530-543
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• 2006

Adeonoid cystic carcinoma (ACC) is one of the most common malignant tumors of salivary glands. It is characterized by a relentless regrowth especially around nerve tissues and a high rate of hematogenous distant metastasis. Clinically most deaths from salivary ACC are caused by delayed lung metastases that are resistant to conventional chemotherapy. So, knowledge of cellular and molecular properties that influence the dissemination of metastatic tumor cells, is important for new treatment strategies of metastatic lesions. We determined expressions of angiogenic signaling molecules microvessel density (MVD) using surgical specimens of human salivary ACC. Protein expressions of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, activated VEGFR-2, and human CD31 were assessed in 20 cases of salivary ACC by immunohistochemical staining. Most of the tumors, especially ACC with a tubulocribriform pattern, were positive for antibodies of VEGF, VEGFR-2, and activated VEGFR-2. The overall percentages of the 20 specimens expressing VEGF, VEGFR-2, activated VEGFR-2 were 90, 95, and 95%, respectively. Immunoreactivities of the biomarkers in salivary ACC were higher than those in normal salivary gland. Furthermore, immune-related cells as well as tumor cells expressed VEGF/VEGFR-2. Microvessel density of salivary ACC was higher than that of normal salivary gland (P<0.05). Taken together, angiogenic signaling molecules are actively expressed in salivary ACC. And we suggest that these molecules may have critical role in the hematogenous spread of salivay ACC, which has a propensity for delayed lung metastasis. Therefore, these biomarkers can be molecular targets for therapy of metastasis of salivary ACC.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1502-1506
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• 2006

To investigate the inhibitory effects of Citaowan (CTW) on the growth and angiogenesis of breast cancer in vivo. Orthotopic breast cancer model was established by injection of MDA-MB-231 cells into mammary fat pad of nude mice. Seven weeks after injection, CTW was orally administered at dose of 50, 100 mg/mouse every day for 40 days. Body weight, tumor volume, tumor apoptosis, microvessel density and tumor proliferation were evaluated, after the mice were sacrificed. The body weight and tumor volume were not significantly changed in CTW group compared with the control group. Tumor apoptosis, proliferation and microvessel density were significantly reduced in CTW group (100 mg/mouse) compared with the control group. These data indicate that CTW has anti-angiogenic and proapoptotic effects on breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4965-4969
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• 2015

LCN2 (Lipocalin 2) is a 25 KD secreted acute phase protein, reported to be a novel regulator of angiogenesis in breast cancer. Up regulation of LCN2 had been observed in multiple cancers including breast cancer, pancreatic cancer and ovarian cancer. However, the role of LCN2 promoter methylation in the formation of microvessels is poorly understood. The aim of this study was to analyze the association of LCN 2 promoter methylation with microvessel formation and tumor cell proliferation in breast cancer patients. The LCN2 promoter methylation status was studied in 64 breast cancer tumors by methylation specific PCR (MSP). Evaluation of microvessel density (MVD) and Ki67 cell proliferation index was achieved by immunohistochemical staining using CD34 and MIB-1 antibodies, respectively. LCN2 promoter unmethylation status was observed in 43 (67.2%) of breast cancer patients whereas LCN2 methylation status was seen in 21 (32.8%). Further, LCN2 promoter unmethylation status was associated with aggressive tumor phenotype and elevated mean MVD in breast cancer patients.

• 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.