Positive Rates Of Vascular Endothelial Growth Factor Research Articles

Vascular endothelial growth factor expression and significance in different grades of the Breast Imaging Reporting and Data System*

Abstract Objective Mammography is the only modality proven to reduce mortality in breast cancer, and ultrasonography is a well-known adjunct to mammography screening. The Breast Imaging Reporting and Data System (BI-RADS) classification is a practical tool and is correlated with histopathology and combined use with triple assessment (examination, imaging, and biopsy) of palpable diagnostic cases. This study aimed to investigate the relationship between vascular endothelial growth factor (VEGF) expression and different grades of BI-RADS in breast cancer. Methods Ninety-six patients with breast carcinoma were evaluated using BI-RADS by ultrasonography, mammography, and a combination of both modalities. In the combined imaging assessment, BI-RADS 1-4a grade was considered when the score of ultrasonography and mammography was lower than 4a, and BI-RADS 4b-5a grade was considered when the score of ultrasonography and mammography was higher than 4a. Immunohistochemical Ultra SensitiveTM S-P method was employed to evaluate the expression of VEGF in 96 patients. Fifty patients with benign breast disease were selected as the control group. The relationship between VEGF expression and different grades of BI-RADS and that between VEGF expression and other standard prognostic parameters associated with invasive breast cancer, such as size, grade, cancer stage, and metastasis were analyzed. Results The sensitivities of ultrasonography and mammography alone was 74.0% and 84.4%, respectively; However, the sensitivity of their combination increased to 90.6%. The positive rates of VEGF in invasive breast cancer BI-RADS 4b-5 (59/87, 67.8%) were higher than those in BI-RADS 4a (3/9, 33.3%, P < 0.05) and benign breast disease tissues (BI-RADS 1-4a, 11/50, 22.0%) (P < 0.05). There was a positive correlation between VEGF overexpression and BI-RADS 4b-5, histological grade (III), lymph node metastasis, and distant metastasis of invasive breast cancer. VEGF expression was not related to the age and size of the tumor in each group (P > 0.05). Conclusion There was a positive correlation between VEGF overexpression and BI-RADS 4b-5 grade. The overexpression of VEGF might be an important biological marker for the invasion and metastasis of breast cancer.

Clinical research on the expression of three vascular regulatory factors in different morphological regions of Marjolin ulcer and their relationship with angiogenesis

Objective: To investigate the expressions of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1α), and epidermal growth factor receptor (EGFR) in different morphological regions of Marjolin ulcer and their clinical relationship with angiogenesis. Methods: From January 2012 to December 2017, the patients admitted to our hospital who met the inclusion criteria were selected, including 92 patients with Marjolin ulcer [56 males and 36 females, aged (55±15) years], 100 patients with chronic non-cancerous skin ulcer [59 males and 41 females, aged (51±16) years], and 100 patients performed with other skin-related surgery [58 males and 42 females, aged (52±15) years], and they were enrolled into Marjolin ulcer group (MU), chronic non-cancerous ulcer group (CNU), and other skin surgery group (OSS) respectively. The etiology, pathogenic site, ulcer diameter, and course of patients in group MU were retrospectively analyzed. Ulcer tissue specimens from patients of group MU and group CNU and specimens of normal skin tissue attached to the tissue resected during operation from patients of group OSS were collected. The expressions of VEGF, HIF-1α, EGFR, and CD34 in the above-mentioned tissue and the surrounding normal skin, ulcer, epitheliomatous hyperplasia, and canceration areas in Marjolin ulcer tissue were detected by immunohistochemical method, and the positive expression rate and protein expression level were calculated. Data were processed with Pearson chi-square test, Mann-Whitney U test, Bonferroni method, and Bonferroni correction, and Spearman correlation analysis was used to analyze the relationship among the total protein expression levels. Results: In group MU, burns accounted for 91.3% (84/92) of the causes of patients, 44.6% (41/92) of the patients had tumors in the lower extremities, 62.0% (57/92) of the patients had skin ulcer diameter of 2.1-5.0 cm, and 75.0% (69/92) of the patients had a course of disease of more than 20 years. The positive rates of VEGF, HIF-1α, and EGFR in ulcer tissue of patients in group CNU were 41.0% (41/100), 77.0% (77/100), and 83.0% (83/100), respectively, significantly higher than those of normal skin tissue of patients in group OSS [12.0% (12/100), 45.0% (45/100), and 67.0% (67/100), χ(2)=21.589, 21.522, 6.827, P<0.01]. The positive rates of VEGF, HIF-1α, and EGFR in ulcer tissue of patients in group MU were 91.3% (84/92), 100.0% (92/92), and 100.0% (92/92), respectively, which were significantly higher than those in corresponding tissue of patients in group CNU and group OSS (χ(2)=53.372, 24.772, 17.159; 120.543, 72.777, 36.661, P<0.01). In ulcer tissue of patients in group MU, the positive expression rates of VEGF in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than the rate in surrounding normal skin area (χ(2)=87.120, 42.368, 89.624, P<0.01); the positive expression rates of VEGF in canceration and ulcer areas were significantly higher than the rate in epitheliomatous hyperplasia area (χ(2)=22.586, 16.060, P<0.01). In ulcer tissue of patients in group MU, the positive expression rates of EGFR in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than the rate in surrounding normal skin area (χ(2)=21.679, 27.600, 27.600, P<0.01), but the positive expression rates of HIF-1α in four morphological areas were similar (χ(2)=3.008, P>0.05). In ulcer tissue of patients in group MU, the protein expression levels of VEGF and CD34 in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than those in surrounding normal skin area (Z=-6.765, -6.819; -6.765, -6.640; -6.765, -6.819, P<0.01), the protein expression levels of VEGF and CD34 in epitheliomatous hyperplasia area were significantly lower than those in ulcer area (Z=-4.484, -5.266, P<0.01), and the protein expression levels of VEGF and CD34 in canceration area were significantly higher than those in ulcer area (Z=-6.427, -6.723, P<0.01) and epitheliomatous hyperplasia area (Z=-6.427, -6.462, P<0.01). In ulcer tissue of patients in group MU, the protein expression levels of HIF-1α and EGFR in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than those in surrounding normal skin area (Z=-6.819, -6.393; -6.819, -6.393; -6.819, -6.393, P<0.01), the protein expression levels of HIF-1α and EGFR in ulcer area were significantly lower than those in epitheliomatous hyperplasia and canceration areas (Z=-6.118, -5.638; -6.640, -6.393, P<0.01), and the protein expression levels of HIF-1α and EGFR in canceration area were significantly higher than those in epitheliomatous hyperplasia area (Z=-6.558, -6.819, P<0.01). In ulcer tissue of patients in group MU, the total protein expression levels of VEGF, HIF-1α, and EGFR were significantly positively correlated with the total protein expression level of CD34 (r=0.772, 0.415, 0.502, P<0.01) respectively; the total protein expression level of EGFR was significantly positively correlated with that of HIF-1α (r=0.839, P<0.01), both of which were significantly positively correlated with the total protein expression level of VEGF (r=0.531, 0.440, P<0.01) respectively. Conclusions: The expressions of VEGF, HIF-1α, and EGFR are the highest in Marjolin ulcer canceration area, and EGFR may promote angiogenesis through HIF-1α or directly increasing the expression of VEGF.

Effects of low concentration 5-fluorouracil and triamcinolone acetonide on ear hypertrophic scar in a rat model

Objective To explore the effect of low concentration 5-fluorouracil combined with triamcinolone acetonide on rabbit ear hypertrophic scar model. Methods White rabbits post-traumatic scars were randomly divided into A , B , C and D groups, each group contained 18 cases. Group A was given triamcinolone acetonide and low concentration 5-fluorouracil, Group B was given low concentration 5 - fluorouracil, Group C was given triamcinolone acetonide and Group D was used as the control group. The dynamic changes of the scar were observed by naked eyes, hematoxylin-eosin (HE) staining and van Gieson (VG) staining through microscope. Vascular endothelial growth factor (VEGF) and CD34 were detected and compared within 4 groups by immunohistochemical staining. Results We successfully established a rabbit ear scar model. It was observed that the scars of Groups A, B and C had been shorter and flatter than Group D, close to the normal tissue. In HE and VG staining, the number of fibroblasts, inflammatory cells, blood vessels in groups A, B and C had been decreased, compared with Group D. Immunohistochemical results showed that the positive rates of VEGF and CD34 from the most to the lest were Groups D, B, C and A. The scar proliferation index from the most to the lest were Groups D, B, C and A. Conclusions The effect of low concentration 5-fluorouracil in treatment of the rabbit ear hypertrophic scar is better than that of triamcinolone acetonide. Low concentration 5-fluorouracil combined with triamcinolone acetonide has a synergistic effect in treatment of hypertrophic scar, which has better effect than that of low concentration 5-fluorouracil or triamcinolone acetonide alone. Key words: Hypertrophic scar; 5-fluorouracil; Triamcinolone acetonide; Vascular endothelial growth factor; CD34

Correlation between perfusion-weighted magnetic resonance imaging parameters and vascular endothelial growth factors, microvascular density, hypoxia-inducible factor 1α

Objective To investigate the relationship between perfusion-weighted magnetic resonance imaging (PWI) parameters and vascular endothelial growth factor (VEGF), microvascular density (MVD) and hypoxia-inducible factor 1α (HIF-1α) in nasopharyngeal carcinoma (NPC). Methods 94 NPC patients were prospectively studied, and the region of interest was noted by fiberscope. Before the treatment , the common magnetic resonance and PWI were used to obtain the images of region of interest and the relative parameters including transfer constant (Ktrans), rate constant of back flux (Kep), extravascular extracellular volume fraction(Ve), fractional plasm volume (fPV) were calculated, then the marking tissues were detected by biopsy. Immunohistochemical staining was conducted to detect the expressions of VEGF, MVD and HIF-1α, and the relationships between the parameters and proteins were analyzed. Results The positive rates of VEGF and HIF-1α in the NPC tissues were 71.27 % (67/94) and 30.85 % (29/94). There was a significant positive correlation between VEGF and MVD [VEGF-positve vs. VEGF-negtive: (31.273 ± 14.81)/mm2 vs. (23.633 ± 16.56)/mm2, r= 0.322, P= 0.037], but the expression of HIF-1α was not significantly correlated with the VEGF and MVD. The significantly positive correlation was found between VEGF and fPV (r= 0.339, P= 0.041), besides, there were no relations among the rest parameters. Conclusion PWI parameter fPV is positively related with VEGF, indicating that PWI could show angiogensis of NPC to some degree, and provide a guidance for predicting the radiosensitivity of NPC. Key words: Nasopharyngeal neoplasms; Magnetic resonance imaging; Perfusion imaging; Vascular endothelial growth factors; Hypoxia-inducible factor 1, alpha subunit; Microvascular density

Serum and tissue vascular endothelial growth factor predicts prognosis in hepatocellular carcinoma patients after partial liver resection.

To explore the effect of vascular endothelial growth factor (VEGF) expression on prognosis of hepatocellular carcinoma (HCC) after partial liver resection. The expression of VEGF in 64 preoperative serum and resection specimens of HCC, confirmed by pathology, was detected by enzymelinked immunosorbent assay (ELISA) and immunohistochemistry. Correlations of VEGF level to clinicopathological features were analyzed. Cox regression model was used to analyze the recurrence risk factors after hepatectomy. Serum level of VEGF in HCC patients was 334.50±247.62pg/mL, significantly higher than healthy control group (p<0.01); it was also significantly higher in recurrent group than in non-recurrent group (p<0.05). VEGF was expressed in cytoplasm of HCC specimens. The positive rates of VEGF was significantly higher in recurrent group than in non-recurrent group (85.0% vs. 54.5%, p<0.05). The 1-, 2- and 3-year disease-free survival rates were significantly higher in VEGF(-) group than in VEGF(+) group (81.3% vs. 52.2%, 68.8% vs. 33.3%, and 62.5% vs. 29.1%, p<0.01). The overall survival rates of VEGF(-) subgroup was borderline significant higher than that of VEGF(+) subgroup (p=0.068). Multivariate analysis revealed that preoperative macroscopically disseminated nodules, tumor micrometastasis, serum and tissue VEGF level were independent recurrence risk factors. Serum and tissue VEGF level of HCC patients ascends distinctly, correlates to the recurrence of HCC after partial liver resection which can be used to estimate the risk of postoperative recurrence of HCC.

Expressions and clinical significances of Livin and vascular endothelial growth factor in human pancre-atic carcinoma

Objective To investigate the expressions of Livin and vascular endothelial growth factor （VEGF）in pancreatic carcinoma and their cilinical significances.Methods The expressions of Livin and VEGF proteins were tested by immunohistochemistry in 68 cases of pancreatic carcinomas and 44 cases of adja-cent paracancerous tissues.Results The positive rates of Livin in pancreatic carcinomas and adjacent paracan-cerous tissues were 73.5% and 4.5% respectively,and the difference was statistically significant （χ2 =48.137,P<0.001）.The positive rates of VEGF in pancreatic carcinomas and adjacent paracancerous tissues were 69.1% and 13.6% respectively,and the difference was statistically significant （χ2 =29.147,P <0.001）.The expressions of Livin and VEGF were related with tumor differentiation （χ2 =6.061,P=0.014;χ2 =6.592,P=0.010）,TNMstage （χ2 =4.175,P=0.041;χ2 =9.992,P=0.002）,lymph node metasta-sis （χ2 =11.731,P=0.001;χ2 =12.002,P=0.001）and neural invasion （χ2 =9.950,P=0.002;χ2 =7.433,P=0.006）.Significantly positive correlation was found between the expressions of Livin and VEGF by using Spearman correlation analysis （r=0.320,P=0.008）.Survival analysis showed that the expressions of Livin and VEGF were independent prognostic factors in pancreatic carcinoma.Conclusion Livin and VEGF involve in the development,migration and metastasis of pancreatic carcinoma.Livin may upregulate the expres-sion of VEGF,which may lead to the angiogenesis and migration in pancreatic carcinoma. Key words: Pancreatic neoplasms; Gene; Vascular endothelial growth factors; Immunohischemistry

Expression and significance of VEGF and p53 in degenerate intervertebral disc tissue

ObjectiveTo investigate the mechanism of expression and significance of vascular endothelial growth factor (VEGF) and p53 in degenerate intervertebral disc tissue. MethodsPathological sections collected from 156 patients with lumbar disc herniation after surgery were tested by immunohistochemistry method, for evaluation of the expression of VEGF and p53 in degenerate intervertebral disc tissue. Results98 cases (62.8%) with vascular infiltration phenomenon are found, and positive rates of VEGF and p53 in degenerate intervertebral disc tissue are 73.42% (116/156) and 58.97% (92/156); co-expression rate is 53.2%(83/156); the expression rates of VEFG and p53 are significantly higher in the tissue with blood vessel infiltration than in the tissue without infiltration; there is a close relationship of VEGF with p53. ConclusionsVEGF and p53 gene synergetic express in degenerate intervertebral disc tissue, working together in neovascularization and infiltration, and accelerating intervertebral disc tissue degeneration.

The regional expression of hypoxia inducible factor-1α in retinoblastoma and its relationships with vascular endothelial growth factor, Bax and Ki-67

Objective To observe the regional expression of hypoxia inducible factor-1α (HIF-1α) in retinoblastoma and its relationships with vascular endothelial growth factor (VEGF), Bax and Ki-67.MethodsImmunohistochemical study for HIF-lα, VEGF, Bax and Ki-67 was performed in 39paraffinaceous examples of retinoblastoma. Each pathological section was divided into five regions: the surface region, the central part, the bottom part, the choroidal region and seeding tumors. The expressions, correlations and distributional differences of these factors were all invested both integrally and regionally. Results In the 39 cases of retinoblastoma, 10 cases (25.6％) were negative for HIF-1α; 29cases (74.4％) were positive for HIF-1α, including 17 cases (43.6％) (+), 12 cases (30.8％) (++).Regionally, HIF-1α was positive in 71.1％, 36.8％, 84.2％, 54.5％ and 82.1％ of the cases in the surface region, the central part, the bottom part, the choroidal region and seeding tumors, respectively, which was statistically reliable (X2 =24.55, P＜0. 001). The positive rate of VEGF, Bax and Ki-67 was 53. 8％,66.7％ and 59.0％, respectively. In different regions, the positive rates of VEGF and Bax were different (X2=26.77, 22.79; P＜0. 001), but there was no regional distinctions in the expression of Ki-67 (X2=0. 47, P=0. 976). Both the expression of VEGF and Bax had a positive correlation with that of HIF-1α(rs=0. 48, 0.39; P=0.002, 0. 021), but there was no relationship between the expressions of Ki-67and that of HIF-1α (rs=0. 09, P=0. 606). Regionally, the expressions of VEGF, Bax and HIF-1α shared similar distributional features: positive rates were higher in the surface region, bottom part and seeding tumors, and were lower in the central part and choroidal region, which was different from the expression of Ki-67. Conclusion The anoxic zones are more likely to be located in the marginal parts in retinoblastoma,and the expressions of VEGF and Bax had a positive correlation with that of HIF-1α in different regions in retinoblastoma. Key words: Retinoblastoma/ therapy; Hypoxia-inducible factor 1, alpha subunit; Vascular endothelial growth factors; Drug resistance, neoplasm

High expressions of vascular endothelial growth factor and platelet-derived endothelial cell growth factor predict poor prognosis in alpha-fetoprotein-negative hepatocellular carcinoma patients after curative resection

To evaluate the prognosis value of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in alpha-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients after curative resection. Tumor tissue microarrays (TMAs) were used to detect the expressions of VEGF and PD-ECGF in consecutive 162 AFP-negative HCC patients undergoing curative resection between 1997 and 2000 in our institute. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Multivariate study with Cox's proportional hazard model was used to evaluate the prognosis-related aspects. The positive rates of VEGF and PD-ECGF in tumor tissues were 59.9% (97/162) and 62.3% (101/162), respectively. Univariate analysis showed that VEGF and PD-ECGF were prognostic factors for relapse-free survival (P = 0.034 and P = 0.033, respectively). Multivariate analyses demonstrated that the co-index (VEGF/PD-ECGF) was an independent prognostic factor for overall survival and relapse-free survival (P = 0.002 and P = 0.000, respectively). The co-index of VEGF and PD-ECGF is a promising independent predictor for recurrence and survival of AFP-negative HCC patients after curative resection.

Expression of angiogenic factors in cerebral arteriovenous malformations

Background In the process of vascularization, vascular endothelial growth factor (VEGF), angiopoietin-2 and Tie2 are involved in the migration, differentiation and proliferation of vascular endothelial cells, and stimulate the rapid angiogenesis; Tie1 and angiopoietin-1 play important roles in facilitating the formation of vascular lumen and maintaining the integrity of vascular wall. Thus the distributions and expressions may be associated with the occurrence of cerebral arteriovenous malformation. Objective To observe the biological effects of angiogenic factors in the occurrence and development of cerebral arteriovenous malformation. Design An observational comparative experiment. Settings Department of Neurosurgery, General Hospital of Shenyang Military Area Command of Chinese PLA; Department of Neurosurgery, General Hospital of Tianjin Medical University. Participants Fresh samples of complete cerebral arteriovenous malformations resected in 47 patients were collected from the Department of Neurosurgery, General Hospital of Tianjin Medical University from August 1999 to May 2001, including 22 males and 25 females, the mean age was 34.5 years. Informed consents were obtained from all the patients or their relatives. The initial symptom was hemorrhage in 28 cases. All the patients were classified according to the clinical imaging data and Spetzler-Martin grading standard, including 11 cases of grade I, 17 cases of grade II, 11 cases of grade III, and 8 cases of grade IV–V. Normal brain tissues resected by decompression due to trauma were taken from 8 patients as controls, including 5 males and 3 females, aging 12–65 years. Methods ▪ The expressions of VEGF, Tie receptors, angiopoietin-1, angiopoietin-2, proto-oncogene c-myc and proliferating cell nuclear antigen(PCNA) in the samples of cerebral arteriovenous malformation were detected with immunohistochemical method. Under light microscope, the positively stained rat-anti-human factor VIII-related antigens (specific marker of vascular endothelial cells) were counted, then the immuno-positive cells of the other antibodies in the visual field of neighboring section which was in “mirror” relation were counted, and the percentage of the latter to the former was considered as the labeling index of positive cells. The immunostaining intensity was classified negative (–): no positive cells; positive (+): number of positive cells < 20%; moderately positive (++): number of positive cells 20%–50%; strongly positive (+++): number of positive cells > 50%. ▪ The differences of the enumeration data were compared with chi-square test, and the correlation were analyzed with the linear correlation analysis. Main outcome measures Expressions and distributions of VEGF, Tie1 and Tie2 receptors, angiopoietin-1, angiopoietin-2, PCNA and c-myc in the samples of cerebral arteriovenous malformation and normal brain tissue. Results ▪ Expressions of angiogenic factors in the control group and cerebral arteriovenous malformation groups of each grade: The positive rates of VEGF, Tie2, angiopoietin-2, c-myc and PCNA expressions in the control group were significantly different from those in the cerebral arteriovenous malformation groups of each grade (χ 2=21.09–34.23, P < 0.05), whereas the positive rates of Tie1 and angiopoietin-1 expressions were close (χ 2=3.43–3.869, P > 0.05). ▪ Expressions of angiogenic factors in hemorrhage group and non-hemorrhage group: The expressions of VEGF, angiopoietin-2 and PCNA in the hemorrhage group were significantly lower than those in the non-hemorrhage group (χ 2=16.22–26.56, P < 0.05). There ware no obvious differences in the expressions of Tie1 and angiopoietin-1 expressions between the hemorrhage group and non-hemorrhage group (χ 2=3.22–3.78, P > 0.05). The VEGF was positively correlated with the expressions of c-myc and PCNA ( r = 0.728, 0.916, P < 0.05). Conclusion ▪ The expressions of angiogenic factors and related receptors may be involved in the process of cerebral arteriovenous malformation, and had important correlation the its clinical grading. ▪ Angiogenic factors may induce the expression of endothelial cell c-myc in cerebral arteriovenous malformation, and then interfere the cell proliferation and apoptosis.

Expression of hypoxia-inducible factor-1-alpha, hypoxia-inducible factor-2alpha and vascular endothelial growth factor in sporadic clear cell renal cell renal cell carcinoma and their significance in the pathogenesis thereof

To investigate the expression of hypoxia-inducible factor (HIF)-1-alpha, HIF-2alpha, and vascular endothelial growth factor (VEGF) in sporadic clear cell renal cell carcinoma (CCRCC) and to analyze the relationship among them. Samples of CCRCC were obtained from 107 patients during resection. Immunohistochemistry was used to detect the expression of HIF-1-alpha, HIF-2alpha, and VEGF in the tumor tissues and normal kidney tissues distant from the tumor. The microvessel density (MVD) was observed by microscopy. HIF-1-alpha and HIF-2alpha were not expressed in the normal kidney tissues. However, in the tumor tissues the HIF-1-alpha positive rate was 69.2% (74/107), significantly lower than that of the HIF-2-alpha (80.5%, 88/107, P = 0.001), the VEGF positive rate was 78.5% (84/107). The VEGF positive rate of the HIF-1-alpha-positive group was 90.5%, significantly higher than that of the HIF-1-alpha-negative group (51.5%, P = 0.001). The VEGF positive rate of the HIF-2-alpha-positive group was 89.8%, significantly higher than that of the HIF-1-alpha-negative group (26.3%, P = 0.001). The MVD of the 64 HIF-1alpha, HIF-2alpha, and VEGF positive samples was 697, significantly higher than that of the 13 HIF-1alpha, HIF-2alpha, and VEGF negative samples (391, P = 0.001). The MVD of the HIF-2alpha positive samples was 678 +/- 324, significantly higher than that of the HIF-2alpha negative samples (383 +/- 293, P = 0.001). The MVD of the VEGF positive samples was 692 +/- 325, significantly higher than that of the VEGF negative samples (384 +/- 269, P = 0.001). Spearman correlation analysis showed that MVD was strongly positively correlated with HIF-2alpha and VEGF. Mann-Whitney U test showed that HIF-1alpha and HIF-2alpha were not correlated with the staging of CCRCC. HIF-2alpha is expressed more frequently in sporadic CCRCC than HIF-1alpha. Both HIF-1alpha and HIF-2alpha upregulate the VEGF expression and angiogenesis, especially HIF-2alpha.

Impact of hypertension on angiogenesis in the tissues of benign prostatic hyperplasia

To investigate the impact of primary hypertension on angiogenesis in the tissues of benign prostatic hyperplasia (BPH). Immunohistochemistry was carried out to examine the expression of CD34, so as to calculate the microvassel density (MVD), and the expression of vascular endothelial growth factor (VEGF) in the tissues of prostatic gland, resected during operation, of 50 simple BPH patients, aged 68.3 (56 approximately 83), and 50 patients with BPH with hypertension, aged 69.0 (55 approximately 91) with a course of hypertension of 16.5 +/- 11.9 years (1 - 41 years). The MVD of the simple BPH group was 23.1 +/- 9.2, significantly lower than that of the BPH complicated with hypertension group (28.2 +/- 9.5, P < 0.01), especially the BPH complicated with hypertension group with a course >/= 15 years (31.3 +/- 8.5). The MVD of the BPH complicated with hypertension group with a course >/= 15 years was significantly higher than that of the BPH complicated with hypertension group with a course < 15 years (25.7 +/- 9.7, P < 0.05). The VEGF positive rate of the stroma of the simple BPH group was 46.0%, significantly lower than that of the BPH complicated with hypertension group (66.0%, P < 0.05), especially that of the BPH complicated with hypertension group with a course >/= 15 years (81.8%). The VEGF positive rate of the stroma of the BPH complicated with hypertension group with a course >/= 15 years was significantly higher than that of the BPH complicated with hypertension group with a course < 15 years (53.6%, P < 0.05). In the group of BPH with hypertension, MVD was positively correlated with the expression of VEGF in the stromal tissue (R = 0.11, P < 0.05). Hypertension may be closely related to the increased expression of VEGF in prostatic stroma. The increased expression of VEGF may induce angiogenesis and consequently lead to clinical progression of BPH in patients with hypertension.

Cyclooxygenase-2 promotes angiogenesis by increasing vascular endothelial growth factor and predicts prognosis in gallbladder carcinoma

To investigate the relationships between the expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and the degree of vascularization, clinicopathologic feature, survival time of patients with gallbladder carcinomas. Sixty-four gallbladder carcinoma specimens were evaluated for COX-2, VEGF expression by immunohistochemical methods. Microvessel counts (MVC) were determined using CD(34). The relationships between COX-2, VEGF expression, CD(34)-stained MVC, clinicopathologic features and survival time were analyzed. The correlations between COX-2 and VEGF expression, CD(34)-stained MVC were also investigated. COX-2, VEGF immunoreactivity were observed in 71.9% (46/64) and 54.7% (35/64) specimens, respectively. The average MVC in 64 cases of gallbladder carcinoma was 57+/-14 per high power vision field. The status of MVC was closely correlated with Nevin staging, tumor differentiation and lymph node metastasis (P<0.01, 0.002, and 0.003, 0.000, respectively). Increased VEGF expression was significantly correlated with tumor differentiation (poorly and moderately>well differentiated, P<0.05, P = 0.016). Clinical stages had no relation with the expression of VEGF (P>0.05, P = 0.612). There was a positive correlation between COX-2 expression and clinical stages. The positive rate of COX-2 was higher in cases of Nevin stages S(4)-S(5) (81.8%) than in those of Nevin stages S(1)-S(3) (50.0%) with a statistical significance (P<0.01, P = 0.009). The expression of COX-2 did not vary with differentiation (P>0.05, P = 0.067). Statistically significant differences were also observed according to lymph node metastasis, COX-2 expression and VEGF expression (P<0.01, 0.000, and 0.001, respectively). There was no relation between VEGF, COX-2 expression, MVC and the age and sex of patients. MVC and VEGF positive rate in the COX-2 positive gallbladder carcinoma tissue was higher than that in the COX-2 negative tissue (P<0.05, 0.000, and 0.032, respectively). Patients with VEGF, COX-2 positive tumors had a significantly shorter survival time than those with negative tumors (P<0.05, 0.004, 0.01, respectively). Augmented tumor neovascularization induced by VEGF may be one of the several effects of COX-2 responsible for poor prognosis of human gallbladder carcinoma. COX-2 inhibitor, either in combination therapy with other agents, or for chemoprevention, may be effective via suppression of angiogenesis in this fatal disease.

The expression of vascular endothelial growth factor,CD44v6 in non-small cell lung carcinoma

To investigate the expression of vascular endothelial growth factor (VEGF), CD44v6 in non-small cell lung carcinoma. The expression of VEGF and CD44v6 in 35 cases I approximately II stages, 27 cases III approximately IV stages and 50 cases with the metastasis of lymph nodes, 12 cases without metastasis of non-small cell lung carcinoma (NSCLC) tissues were studied by SP immunohistochemistry staining, and the 3 years survival rates were calculated in 42 cases patients. The positive rates of VEGF and CD44v6 in NSCLC were 73% and 69%, respectively. They were both higher than those of matched normal lung tissues, P < 0.01. The expression of VEGF and CD44v6 were related to clinical stages and metastasis of lymph nodes significantly. The expression rates of the two markers in NSCLC with the metastasis of lymph nodes were higher than those without metastasis, chi(2) = 7.146 and 5.376 respectively, and those of III approximately IV stages were higher than those of I approximately II Stages, chi(2) = 6.392 and 12.152 respectively. Survival rates of three years were lower to those patients with positive expression of the two makers than those with negative expression. In a multivariate analysis, besides TNM stages and metastasis of lymph nodes, the positive expression of CD44v6 and the positive expression of VEGF were also the independent prognostic factors to affect the Survival time. The VEGF and CD44v6 protein may act as one of important indexes to indicate the process of infiltration and metastasis in NSCLC.

Inhibition effect of vascular endothelial growth factor antisense oligodeoxynucleotides on C6 glioma

Objective: To explore the probability of vascular endothelial growth factor (VEGF) antisense oligodeoxynucleotides as a developing new therapeutic strategy for glioma. Methods: VEGF protein expression was detected by S-P immunohistochemical technique. Tumor cell apoptosis was observed by TUNEL method. Results: Compared with control, VEGF protein expression was inhibited by antisense oligodeoxynucleotides in vitro. And the inhibitory effects increased with the increasing concentration. VEGF positive rate was 82.10% in control group, while in 2.5, 5, 10 µmol/L AODN groups, they were 70.00%, 57.85%, 53.20% respectively. No inhibition effect was found in the cell lines treated with missense and sense oligodeoxynucleotides. In vivo, antisense oligodeoxynucleotides therapy also inhibited VEGF protein expression and induced the increase of apoptotic tumor cells. However, it has no effect on tumor cell proliferation. Conclusion: It is hopeful that VEGF antisense oligodeoxynucleotides may be a new gene therapy method to glioma through its antiangiogenesis effect by inhibition of VEGF.

Expression of cyclooxygenase-2 and vascular endothelial growth factor in pancreatic tumors

Cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) have been reported to be significantly related to carcinogenesis or progression of various cancers. However, there has been no report on the relation between COX-2 and VEGF overexpression in pancreatic tumors. We investigated the overexpression of COX-2 and VEGF immunohistochemically in intraductal papillary-mucinous tumors (IPMT) and invasive ductal carcinoma (IDC) and examined the relationship with clinicopathological factors and the correlation between these immunoactivities in IPMT and IDC. In IPMT, the positive rates of COX-2 overexpression were 0% in 10 areas of hyperplasia, 54.5% of adenoma, 83.3% of intraductal areas of adenocarcinoma, and 66.7% of invasive areas of adenocarcinoma. On the contrary, 47.8% of IDC were positive for COX-2 overexpression. The positive rates of VEGF in IPMT were 10% in areas of hyperplasia, 54.5% of adenoma, 66.7% of intraductal areas of adenocarcinoma and 66.7% of invasive areas of adenocarcinoma. However, in IDC it was 47.8%. Only lymph node metastasis correlated significantly with VEGF overexpression (p=0.04), while the other factors had no significant relationships with either COX-2 or VEGF overexpression. There was a statistically significant correlation between COX-2 and VEGF overexpression in IPMT (p<0.001), in 5 patients with adenoma of which both COX-2 and VEGF were stained in almost exactly the same locations. On the contrary, COX-2 and VEGF overexpression had no statistically significant relationship in IDC. In conclusion, we demonstrate evidence of COX-2 and VEGF overexpression in human pancreatic tumors. Chemoprevention via the suppression of angiogenesis by means of COX-2 inhibitor may be more effective in IPMT than in IDC, because of the strong correlation of both factors especially in IPMT.

Expression of VEGF and its receptors Flt and KDR in gastric cancer

OBJECTIVE: The purpose of the present study was to investigate the correlation between the expression of vascular endothelial growth factor (VEGF), the expression of its receptors, Flt and KDR, and the biological behavior of gastric cancer. METHODS: Sixty cases of gastric cancer that had been diagnosed by surgery and pathology were studied with the method of semiquantitative reverse transcriptase–polymerase chain reaction (RT‐PCR), to determine the expression of VEGF, Flt and KDR in gastric cancer tissue. RESULTS: The positive rates of VEGF, Flt and KDR in gastric cancer were 73.3, 86.7 and 80.0%, respectively. In pericancerous tissue, the rates were 43.3, 33.0 and 30.0%, respectively. There were significant differences between the groups with and without lymph node metastasis (P &lt; 0.01). For gastric cancer patients with lymphatic metastasis, the positive rates for VEGF, Flt and KDR were 90.3, 80.6 and 96.8%, respectively; for patients without lymphatic metastasis, the rates were 51.7, 41.3 and 55.1%; there were significant differences between the groups with and without lymph node metastasis (P &lt; 0.01). The positive rates of VEGF and KDR in well‐differentiated gastric cancer were 40.0 and 46.7%, markedly lower than those of the poorly differentiated and undifferentiated gastric cancer groups. The rate of positive expression of Flt in the well‐differentiated gastric cancer group was 73.3%. There was no significant difference between this rate and that of the poorly differentiated and undifferentiated groups (87.5%). The positive expression of VEGF, Flt and KDR was unrelated to the depth of infiltration. CONCLUSIONS: There are some correlations between VEGF, Flt and KDR and the biological behavior of gastric cancer. Knowing where they are expressed at high rates may be of help in evaluating the prognosis of gastric cancer.

Study on the clinical-pathological significance of microvessel density and vascular endothilial growth factor expression in primary liver cancer

Objective: To evaluate the clinical-pathological significance of intratumoral microvessel density (MVD) and Vascular Endothelial Growth Factor (VEGF) expression in primary liver cancer (PLC). Methods: A retrospective study from 63 postoperative patients all with small PLC (diameter ≤5 cm) was done. One group of 29 patients developed recurrence or metastasis within 2 years. The other group of 34 patients had no evidence of recurrence or metastasis within 2 years. Three sections were taken from each patient. One for H.E. staining, the other two for VEGF and Bio-UEA-I immunohistochemical staining respectively. MVD was counted by endothelial cells, which were highlighted by Bio-UEA-I. Results: The MVD of the recurrence (or metastasis) group (49.6±29.7) were significantly greater than the other, group (22.7±28.2) (P<0.01); The VEGF positive rate of the recurrence group was 86.2% (25/29), the rate of the other group was 47.1% (16/34). the difference between the 2 groups was stafistically significant (P<0.01). The stage of the tumor, the positive rate of satellite nodules and the positive rate of the portal vein embolus were all significantly different between the 2 groups. Conclusion: Besides tumor stage, satellite nodule and portal vein embolus, the MVD and VEGF are also of prognostic significance.

Clinical significance of micrometastasis in bone marrow of patients with gastric cancer and its relation to angiogenesis.

BACKGROUND: Detection of micrometastasis is an important problem of clinical significance for a better understanding and control of tumor progression, which will improve patients' survival time.METHODS: To identify micrometastases in bone marrow, an immunocytochemical assay for epithelial cytokeratin protein was performed in 106 patients with primary gastric cancer. Also, in 40 of the 106 patients, vascular endothelial growth factor (VEGF) expression and intratumoral vessel density were examined by an immunohistochemical staining method.RESULTS: Of the 106 patients, 22 (20.8%) presented with cytokeratin-positive cells in bone marrow at the time of primary surgery. The positive findings were related to depth of invasion, peritoneal dissemination, and liver metastasis. Patients with cytokeratin-positivity in bone marrow had a higher VEGF positive rate (73%; 8/11) than did cytokeratin-negative patients (48%; 14/29). Intratumoral vessel density in VEGF-positive patients was 26.9 +/- 10.3, which was significantly higher than that in VEGF-negative patients (13.2 +/- 8.7, P < 0.05). Thus, the presence of cytokeratin-positive cells in bone marrow was closely related to angiogenesis in the primary tumor.CONCLUSIONS: Cytokeratin staining can be useful for identifying patients at high risk for metastasis. Prophylactic lymph node dissection, adjuvant chemotherapy, and antiangiogenic treatment may be necessary for patients with micrometastasis.