Increased expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 after pilocarpine-induced status epilepticus in mice

Vascular endothelial growth factor (VEGF)-C and its receptor, vascular endothelial growth factor receptor (VEGFR)-3, are responsible for lymphangiogenesis in both embryos and adults. In epilepsy, the expression of VEGF-C and VEGFR-3 was significantly upregulated in the human brains affected with temporal lobe epilepsy. Moreover, pharmacologic inhibition of VEGF receptors after acute seizures could suppress the generation of spontaneous recurrent seizures, suggesting a critical role of VEGF-related signaling in epilepsy. Therefore, in the present study, the spatiotemporal expression of VEGF-C and VEGFR-3 against pilocarpine-induced status epilepticus (SE) was investigated in C57BL/6N mice using immunohistochemistry. At 1 day after SE, hippocampal astrocytes and microglia were activated. Pyramidal neuronal death was observed at 4 days after SE. In the subpyramidal zone, VEGF-C expression gradually increased and peaked at 7 days after SE, while VEGFR-3 was significantly upregulated at 4 days after SE and began to decrease at 7 days after SE. Most VEGF-C/VEGFR-3-expressing cells were pyramidal neurons, but VEGF-C was also observed in some astrocytes in sham-manipulated animals. However, at 4 days and 7 days after SE, both VEGFR-3 and VEGF-C immunoreactivities were observed mainly in astrocytes and in some microglia of the stratum radiatum and lacunosum-moleculare of the hippocampus, respectively. These data indicate that VEGF-C and VEGFR-3 can be upregulated in hippocampal astrocytes and microglia after pilocarpine-induced SE, providing basic information about VEGF-C and VEGFR-3 expression patterns following acute seizures.

Research on influence mechanism of G protein coupled receptor kinase interacting protein 1 on differentiation of bone marrow mesenchymal stem cells into endothelial cells / 中国修复重建外科杂志

Objective: To investigate the mechanism of G protein coupled receptor kinase interacting protein 1 (GIT1) affecting angiogenesis by comparing the differentiation of bone marrow mesenchymal stem cells (BMSCs) differentiated into endothelial cells between GIT1 wild type mice and GIT1 gene knockout mice.

Clinical value of the VEGF-C and VEGF-R3 in peripheral blood of patients with lung cancer / 国际肿瘤学杂志

Objective To investigate the relationship between the expression of vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGF-R3) in peripheral blood of patients with lung cancer and the pathological characteristics, and to assess the ability to evaluate lymphatic and distant metastasis of the two marks.Methods VEGF-C and VEGF-R3 were detected by enzyme-linked immunosorbent assay (ELISA) in 124 patients with lung cancer and 30 normal controls, and used to analyze the relationship with the pathological characteristics of lung cancer.Results The serum levels [M(QR)] of VEGF-C and VEGF-R3 in patients with lung cancer were 283.57 (120.70) pg/ml and 62.72 (43.02) ng/ml, significantly higher than the control whose VEGF-C and VEGF-R3 were 234.62 (129.20) ng/ml and 43.08 (17.07) pg/ml, respectively (Z=-2.840, P=0.005;Z=-3.834, P<0.001).No correlation was found between the expression of VEGF-C and age, sex, primary tumor site, T stage (Z=-0.949, P=0.343;Z=-0.454, P=0.649;Z=-1.168, P=0.243;Z=-1.694, P=0.090).But the expression of VEGF-C was significantly related with pathologic type, N stage and M stage (χ2=8.829, P=0.012;χ2=27.148, P<0.001;Z=-2.221, P=0.026).However, the expression of VEGF-R3 was not correlated with age, sex, the site of the primary lesion, pathological type and T, N, M stage (Z=-0.558, P=0.577;Z=-0.599, P=0.549;Z=-0.703, P=0.482;χ2=1.166, P=0.558;Z=-0.680, P=0.496;χ2=0.353, P=0.950;Z=-1.523, P=0.128).Conclusion The expressions of VEGF-C and VEGF-R3 in patients with lung cancer are higher than those in normal control, and the expression of VEGF-C is related with patho-logic type, N stage and M stage.The detection of VEGF-C in peripheral blood of lung cancer is expected to be an assistant marker for the evaluation of lymph node metastasis and blood metastasis, but VEGF-R3 does not show its value.

Tumor-associated M2 macrophages enhance migration and invasion of lung adenocarcinoma A549 cells by regulating the expression of VEGFR3 / 肿瘤

Objective: To investigate the role of M2-type macrophages in migration and invasion of lung adenocarcinoma A549 cells, and to explore the possible mechanism and the related signaling pathway. Methods: PMA (phorbol 12-myristate 13-acetate) was used to induce THP-1 cells into M2- type macrophages. The non-contacting co-culture model of M2-type macrophages and A549 cells was established by Transwell method, then the co-culture medium was collected. The migration and invasion abilities of A549 cells after treatment with co-culture medium (named as CO-A549 cells) were detected by the wound-healing assay and Transwell chamber invasion assay, respectively. The expression levels of vascular endothelial growth factor receptor 3 (VEGFR3) and vascular endothelial growth factor-C (VEGF-C) in CO-A549 cells were detected by Western blotting. After treatment with VEGFR3 inhibitor MAZ51, the migration and invasion abilities of CO-A549 cells were detected by wound-healing assay and Transwell invasion assay again, and the expression level of phospho-extracellular signal-regulated protein kinase (p-ERK) in CO-A549 cells was detected by Western blotting. Finally, the expression level of matrix metalloproteinase 2 (MMP-2) mRNA in CO-A549 cells after treatment with MAZ51 or U0126, an inhibitor of mitogen-activated protein kinase (MAPK)/ERK pathway, was detected by RT-PCR. Results: M2-type macrophages were induced for from THP-1cells by PMA. After treatment with the co-culture medium, the migration and invasion abilities of A549 cells were significantly enhanced (both P < 0.01), the expression level of VEGFR3 was significantly improved (P < 0.01). After inhibition of VEGFR3, the migration and invasion abilities of CO-A549 cells were decreased (P < 0.01, P < 0.05), and the expression level of p-ERK was down-regulated (P < 0.05). The expression of MMP-2 mRNA was down-regulated in CO-A549 cells after treatment with MAZ51 or U0126 (both P < 0.05). Conclusion: M2-type macrophages which were induced by PMA from THP-1 cells can promote the migration and invasion of A549 cells by up-regulating the expression of VEGFR3. The mechanism may be related to the activation of the MAPK/ERK signaling pathway.

A rare case of pulmonary lymphangiomatosis from the tribal zone of central India.

Lymphangiomatosis, a rare disease, occurs in individuals of any age, regardless of gender, but is predominantly seen in younger individuals. It often presents with pulmonary involvement, although, the bones, spleen and liver can also be affected. Histologically, pulmonary involvement includes proliferation, complex anastomoses and secondary dilatation of the lymphatic vessels. Clinically presentation is often variable but pulmonary involvement is affected more common than other involvements. Diagnosis is made histologically but radiologically can suggest diseases. Treatment is only supportive and symptomatic.

Correlation studies of VEGF-C/D and its receptor with lymph node metastasis in gastric cancer / 中国肿瘤临床

The lymphatic vessel is a crucial pathway for tumor metastasis. The discovery of more lymphatic growth factors and lymphatic vessel markers signifies the significant progress of studies on the role of vascular endothelial growth factor-C/D (VEGF-C/D) and one of its specific receptors in the mechanisms of tumor lymph-angiogenesis and lymph node metastasis. VEGF-C/D expression is related to the clinicopathologic features of gastric cancer, including lymph metastasis, micro-lymphatic vessel density in the paraneo-plastic tissues, survival rate, and prognosis. Experimental animal models and in vitro experiments show that suppression of VEGF-C/D expression is beneficial in gastric cancer treatment. This article provides an overview of the association between VEGF-C/D and lymph node metastasis in gastric cancer.

Research advancement in lymphangiogenesis in renal cell carcinoma / 中国肿瘤临床

Renal cell carcinoma (RCC) is a common urologic malignancy, comprising 2% to 3% of all malignant diseases. Lym-phangiogenesis significantly affects the lymphatic metastasis of tumors. Vascular endothelial growth factors and their receptors have important functions in the spread of cancer cells. Vascular endothelial growth factor-C, which links the vascular endothelial growth factor receptor-3, can increase lymphangiogenesis and promote lymphatic metastasis. These findings direct research efforts toward lymphangiogenesis in malignant diseases and a possible targeted therapy. An increasing number of studies on the lymphatic vessel of renal cell carcinoma have drawn considerable interest in the treatment of renal cell carcinoma. This paper summarizes recent studies on lymphangiogenesis and the clinical significance of renal cell carcinoma.

The relation between vascular endothelial growth factor receptor 3 and bladder cancer lymphatic metastasis / 中国基层医药

Objective To explore vascular endothelial growth factor-C (VEGF-C),vascular endothelial growth factor receptor 3 (VEGFR-3) in the bladder cancer tissue of the expression and the relationship with the tumor lymph node metastases of bladder cancer tissue,Methods The VEGF-C,VEGFR-3 expression was detected by Elivision TM plus two footwork.Results In 18 cases of bladder cancer organization,VEGF-C expression positive rate was 72％,VEGFR-3 express positive rate was 67％.VEGF-C in the bladder cancer of the transfer of the expression level compared to the lymph nodes of the transfer of the lymph node has not occurred to high.Conclusion In the bladder cancer organization and the surroundinglymph nodes,VEGF-C,VEGFR-3 expression level and lymph node metastasis is closely related.VEGF-C,VEGFR-3 expression intensity can be used as a lymph node metastasis in bladder cancer index.

Expression of hMAM, VEGF-C and VEGFR-3 in breast cancer tissues and its relation with prognosis / 第二军医大学学报

Objective To study the expression of human-mammaglobin (hMAM) and vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor 3 (VEGFR-3) in breast cancer tissues, and to analyze its relationship with biological characteristics and prognosis of breast cancer. Methods The expression of hMAM, VEGF-C andVEGFR-3 was determined by immunohistochemical technique in 116 breast cancer tissues and 44 adjacent normal tissues (from cancer tissue≥ 5 cm) using tissue microarray technology (TMA). Results (1) The positive rates of hMAM, VEGF-C and VEGFR-3 in primary breast carcinoma tissues were significantly higher than those in the adjacent normal tissues (59. 48% [69/116] vs 0. 00%, 50. 86% [59/116] vs 9. 09% and 61. 20% [71/116] vs 18. 18%, respectively, all P<0. 01). (2)The positive rates of hMAM, VEGF-C and VEGFR-3 were significantly correlated with axillary lymph node metastasis, and the positive rates of hMAM, VEGFR-3 were significantly correlated with histological gradings (all P<0. 05). (3) Spearman rank correlation analysis showed that the positive rates of hMAM, VEGF-C and VEGFR-3 in breast cancer tissues were all significantly correlated with each other, with correlation coefficients being 0. 278, 0. 280, and 0. 244, respectively, all P<0. 05). (4)Kaplan-Meier survival analysis showed that the disease-free survival and 5-year overall survival of patients with negative expression of HMAM, VEGF-Cand VEGFR-3 were significantly prolonger compared to those with positive expression (Log-rank test, P< 0. 05). Conclusion hMAM, VEGF-C and VEGFR-3 are highly expressed in breast cancer patients, which might be associated with the invasion and metastasis of breast cancer, and hMAM expression might be related to the lymphangiogenesis of breast cancer.

The differential expression of vascular endothelial growth factor and its receptor subtypes in myocardial infarction rats / 中国医师杂志

Objective To investigate expressions of the vascular endothelial growth factor (VEGF) family and their receptors in cardiac repair/remodeling after myocardial infarction (MI).Methods The infarcted rat heart model were constructed,real time PCR (RT-PCR) and Western blots (WB) were used.Results Compared to the normal myocardium,VEGF-A was significantly decreased in MI group during the 42 days observation period but decreased at day 1,which was 0.89 ±0.04 of control group in D1,0.25 ±0.03 of control in D14; VEGF-B was significantly suppressed in the infarcted heart,which level was 0.09 ± 0.04 of control; However,VEGF-C and VEGF-D were markedly increased in the infarcted heart in MI group,which was 5.31 ± 0.21 and 9.24 ± 0.47 times of control.Meanwhile,VEGFR-1 and 2 were 0.11 ± 0.02 and 0.14 ± 0.04 of control in the infarcted heart,but VEGFR-3 was significantly increased in blood vessels,6.81 ± 0.42 times of control group.Conclusions VEGF isoforms and VEGFR subtypes were differentially expressed in the infarcted heart.It suggests that these isoforms may regulate multiple responses during cardiac repair/remodeling.

Effects of VEGF-C, VEGFR-3 and LYVE-1 on Lymphangiogenesis and Prognosis in Gastric Cancer / 天津医药

Objective To study the role of expressions of vascular endothelial growth factor C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3) and lymphatic vessel hyaluronan receptor-1(LYVE-1) on the lymphangio-genesis and prognosis in gastric cancer. Methods The tissue microarray technology was used to detect the expressions of VEGF-C, VEGFR-3 and LYVE-1 in 125 gastric cancer specimens, 96 adjacent normal tissues and 20 benign gastric lesion samples. The lymphatic vessel density (LVD) marked by Podoplanin was detected as well. Results The positive rates of VEGF-C, VEGFR-3 and LYVE-1 in gastric cancer tissues were 62.4%, 56.0%and 58.4%, which were significantly higher than those in adjacent normal tissues (10.4%,12.5%and 9.4%) and benign gastric lesion tissues (20%, 30%and 25%, P<0.05). The LVD score was significantly higher in gastric intra-tumoral and peri-tumoral samples (2.98±0.81 and 4.22±1.09) than that in adjacent normal tissues or benign gastric lesion samples (1.82±0.63 or 0.89±0.45, P<0.01). The LVD score was significantly higher in peri-tumoral samples than that of intra-tumoral samples (P<0.01). There was a positive relationship between expression levels of VEGF-C,VEGFR-3 and LYVE-1 with LVD (P<0.05). The positive expressions of the three indexes were the risk factors of lymph node metastasis and distant metastasis (P<0.05). There was a significantly longer 5-year survival rate in patients with negative expression of the three indexes (P<0.05). Conclusion VEGF-C, VEGFR-3 and LYVE-1 proteins were positively highly expressed in gastric cancer tissues, which were risk factors affecting the progno-sis of gastric cancer. The expression levels of the three indexes can be used to predict the prognosis and lymphangiogenesis of gastric cancer.

Microvessel and Lymphatic Vessel Density and VEGFR-3 Expression of Papillary Thyroid Carcinoma with Comparative Analysis of Clinicopathological Characteristics

BACKGROUND: This study was done to see if there were correlations between anatomic and molecular parameters such as microvessel density (MVD), lymphatic vessel density (LVD), and vascular endothelial growth factor receptor (VEGFR)-3 expression and various clinical parameters for papillary thyroid carcinomas of size > 1.0 cm (PTCs) and size 45 years old (more apparent in the PTC group) and LVD had suggestive correlations with multicentricity and extrathyroidal extension depending on analytic conditions. CONCLUSIONS: Since LVD showed variable correlations with clinical variables for papillary carcinoma of the thyroid depending on analytic conditions, the individually planned treatments based on overall clinicopathological factors are advised.

Relationship between Vascular Endothelial Growth Factor Receptor-3 and Occult Metastasis in Early-Stage Tongue Cancer / 天津医药

Objective:To detect the expression of vascular endothelial growth factor receptor-3(VEGFR-3)in earlystage tongue cancer and the relationship with occult metastasis thereof.Methods:The expression of VEGFR-3 was examined in paraffin-embedded specimens from 62 patients with early-stage tongue cancer by immunohistochemical staining.The relationship was analyzed between the expression of VEGFR-3 and size,occult metastasis and differentiation of early-stage tongue cancer.Results:The positive expression of VEGFR-3 mainly located in the lymphatic endothelial cells of peritumoral areas and negative expression in tumor area.The higher expression of VEGFR-3 was found in patients with occult metastasis.The expression of VEGFR-3 was significantly higher in patients of Ⅱ-Ⅲ grade than that of patients in I grade carcinoma(t=4.77,P ＜ 0.05).The expression of VEGFR-3 was higher in patients with occult metastasis than that in patients with negative lymph node(t=6.33,P ＜ 0.05).But there were no significant correlation between the expression of VEGFR-3 and the age,gender and size of tumor in patients.Conclusion:The value of VEGFR-3 can be a useful indicator to evaluate the occult metastasis of early-stage tongue cancer.

The significance of expression of VEGFR-3 signaling associated protein in thyroid cancer / 中华内分泌外科杂志

Objective To investigate the involvement of VEGFR-3 signaling pathway in lymphatic metastasis of thyroid cancer. Methods The expression of VEGFR-3 mRNA in thyroid carcinoma and normal thyroid tissue was detected by RT-PCR. The expression of VEGFR-3 mRNA and the lymphatic vessel density (LVD) in thyroid carcinoma and normal thyroid tissue was measured by immunohistochemical staining. Results All thyroid cancer samples expressed VEGFR-3 and the expression rate of VEGFR-3 in thyroid carcinoma was significantly higher than that in the normal thyroid group ( P ＜ 0. 05 ). LVD in thyroid cancer was significantly higher than that in normal control. LVD with lymph nodes metastasis ( N + ) was significantly higher than that without lymph node metastasis (NO) (P ＜ 0. 05). Conclusions There is upregulatin of VEGFR-3 expression in thyroid carcinoma. The higher the expression of VEGFR-3, the severer of lymph node metastasis. VEGFR-3 receptor-mediated signal transduction pathway might be an important factor of thyroid cancer lymph node metastasis.

Expression and significance of PCS, PC7, VEGF-C, VEGF-D and VEGFR-3 mRNA in non-small cell lung cancer / 中国癌症杂志

Background and purpose: Infiltration and metastasis are characteristic of the biological behavior of cancer. Blood circulation and lymphatic spread are two important ways for neoplasm metastasis. The lymphatic vessel is one of the earliest routes for solid neoplasm metastasis. However, compared to tumor blood vessels, there were only a few studies on the research for lymphatic vessel spread. In recent years, with the identification of vascular endothelial growth factor-C (VEGF-C), VEGF-D and lymphatic endothelial markers including lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3), glomerular podocyte membrance mucoprotein (podoplanin) and the homeobox transcription factor (Prox-1), lymphangiogenesis has become one of the important areas in the study of tumor metastasis. This paper was to study the expression of proprotein convertase (PC)5, PC7, VEGF-C, VEGF-D and their receptor VEGFR-3 in patients with non-small cell lung cancer (NSCLC) and their clinico-pathoiogical value. Methods: Twenty specimens of the NSCLC, peritumoral tissues as experimental group and nine pulmonary benign diseases as control group were studied. The expression of PC5, PC7, VEGF-C, VEGF-D and VEGFR-3 mRNA in specimens of those tissues were studied by real-time quantitative reverse transcriptase polymerase chain reaction (real-time quantitative RT-PCR). Results: ①The expressions of PC5, PC7, VEGF-C, VEGF-D, VEGFR-3 mRNA in specimens of NSCLC were significantly higher than those of the peritumoral and pulmonary benign diseases tissues (P<O.05).② The expressions of PC5, PC7, VEGF-C, VEGF-D and VEGFR-3 mRNA in NSCLC were not correlated with age, gender, site and dimension of lesion, types of histological and degree of differentiation, but correlated significantly with lymph node metastasis (P=0.000, P=0.000,P=0.012,P=O.000, P=0.004) and pTNM stage (P=0.011, P=0.012, P=0.O13, P=0.011, P=0.028).③Significant correlationsbetween PC5 and VEGF-C (r=0.461, P=0.041), PC5 and VEGF-D (r=0.793, P=0.000), PC5 and VEGFR-3 (r=0.498, P=0.026), PC7 and VEGF-C (r=0.450, P=0.047), PC7 and VEGF-D (r=0.699, P=0.001), PC7 and VEGFR-3 (r=0.616, P=0.004), VEGF-C and VEGF-D (r=0.532, P=0.016), VEGF-C and VEGFR-3 (r=0.607, P=0.001), VEGF-D and VEGFR-3 (r=0.451, P=0.048) mRNA were observed in NSCLC. Conclusion: Non-small cell lung cancer cells may secrete lymphangiogenetic growth factors like VEGF-C, VEGF-D and their receptor VEGFR-3 and may associate with lymphatic metastasis of NSCLC through their downstream pathways. The expression of VEGF-C, VEGF-D, VEGFR-3, PC5 and PC7 may serve as important markers for evaluation of lymphatic metastasis and prognosis in patients with NSCLC.

Expression of VEGF-C and VEGFR-3 in breast cancer tissue and its clinical significance / 国际检验医学杂志

Objective To investigate the expression of vascular endothelial cell growth factor-C (VEGF-C) and its receptor--vascular endothelial cell growth factor receptor-3 (VEGFR-3) in breast cancer tissue and its correlation with metastasis of lymphonodi axillares.Methods Fifty-eight cases of breast cancer samples and 10 cases of tumor adjacent non-carcinomatous tissue were measured by immunohistochemical staining for expression of VEGF-C and VEGFR-3. Their expression rates were compared between axillary lymph node metastasis and non-metastasis groups.Results The positive rates of VEGF-C and VEGFR-3 as well as the number of VEGFR-3 positive vessels were significantly higher than those in lymph node non-metastasis group (87.5% vs 55.9%; 83.3% vs 38.2%; 8.54±2.54 vs 4.73±2.46, respectively).Conclusion The high expression of VEGF-C and VEGFR-3 as well as the increase in the number of VEGFR-3 positive vessels are related to lymph node metastasis of human breast cancer. VEGF-C/VEGFR-3 system may be a new specific target which contributes to blockage of lymphatic metastasis in breast cancer.

Correlation of Vascular Endothelial Growth Factor-D Expression and VEGFR-3-Positive Vessel Density with Lymph Node Metastasis in Gastric Carcinoma

Lymph node metastasis is an important prognostic factor in gastric cancer. Vascular endothelial growth factor-D (VEGF-D) is a lymphangiogenic growth factor that activates VEGF receptor (VEGFR)-3, a receptor expressed in the lymphatic endothelium. We investigated the clinical value of VEGF-D expression and VEGFR-3 positive vessel density in gastric carcinoma with regard to lymphangiogenesis. Immunohistochemical staining was used to determine the expression of VEGF-D and VEGFR- 3 in specimens from 104 cases of resected gastric cancer. VEGF-D expression was observed in 62.5% of the gastric cancers and in 9.6% of the non-neoplastic gastric tissue. The VEGFR-3-positive vessel density was significantly greater in the VEGFD positive group than the negative group. VEGF-D expression was significantly associated with lymph node metastasis, increased serum CEA levels, and the nonsignet ring cell type. The VEGFR-3-positive vessel density was correlated with tumor size, lymphatic invasion, and lymph node metastasis. The VEGF-D expression and high VEGFR-3-positive vessel density were significant poor prognostic factors for relapse-free survival. These results suggest that VEGF-D and VEGFR-3-positive vessel density are potential molecular markers that predict lymphatic involvement in gastric carcinoma.

Expression of VEGF-C and VEGFR-3 in hepatocellular carcinoma and their significance / 肿瘤研究与临床

Objective To investigate vascular endothelial growth factor-c (VEGF-C) and vascular endothelial growth factor receptor-3(VEGFR-3) mRNA expression, microvessels density (MVD) and lymphatic microvessels density (LVD) in human hepatocellular carcinoma and normal liver tissue. Try to illuminate the relationship among VEGF-C,VEGFR-3,MVD,LVD and the clinical pathological features of hepatocellular carcinoma. Methods Liver tissue of 60 cases definitely diagnosed as hepatocellular carcinoma and 20 normal cases were collected. VEGF-C and VEGFR-3 mRNA expression were examined by RT-PCR, MVD and LVD were examined by immunohistochemistry staining. Relationship between these indexes and clinical pathological features of hepatocellular carcinoma was also analysed. Results VEGF-C and VEGFR-3 mRNA expression, MVD and LVD in hepatocellular carcinoma were higher than those in normal liver tissue (P<0.01); In hepatocellular carcinoma tissue, expression of VEGF-C mRNA positively related with VEGFR-3 mRNA, MVD and LVD(P<0.01). VEGF-C and VEGFR-3 expression positively related with portal vein tumor thrombus, intrahepatal metastasis and lymph node metastasis (P<0.01). MVD positively related with portal vein tumor thrombus and intrahepatal metastasis (P<0.01). LVD positively related with lymph node metastasis (P<0.01). Conclusion VEGF-C and VEGFR-3 expression increase in hepatocellular carcinoma tissue. They might play roles in tumor invasion and metastasis by inducing angiogenesis and lymphangiogenesis.

Effects of dexamethasone on VEGF-C and VEGFR-3 in primary culture in vitro of laryngeal squamous carcinoma tissue / 肿瘤研究与临床

Objective To explore the effect of VEGF-C,VEGFR-3 gene in primary culture in vitro of laryngeal squamous carcinoma tissue by dexamethasone (DEX). Methods Applying the technique of Drimary tissue cuiture in vitro,twelve specimens,which were identified pathologically as laryngeal squamous cell carcinoma,were cultured.After succeeded culture of twelve specimens,the cells were divided in to two groups.One continued to cuhum,another gave 10-7 mol/L of DEX.VEGF-C and VEGFR-3 gene express in 12 cases of cell were examined by reverse transcription polymerase chain reactions(RT-PCR).Results The frequency of VEGF-C(83%) and VEGFR-3(58%) in primary culture in wtro of laryngeal squamous carcinoma tissue were higher than that of the primary culture in vitro of laryngeal squamous carcinoma tissue by dexamethasone (DEX) (25%,8%P＜0.05).Conclusion The expressions of VEGF-C and VEGFR-3 in Drimary culture in vitro of laryngeal squamous carcinoma tissue by DEX are decreased.It may provide guide to apply DEX in clinic laryngeal squamous carcinoma chemotherapy and laryngeal squamous carcinoma laryngeal obstruction.

Expressions of vascular endothelial growth factor D and its receptor Flt-4 in human pancreatic cancer and their significance / 肿瘤

Objective: To study the expressions of vascular endothelial growth factor D (VEGF-D) and its receptor fms-like tyrosine kinase-4 (Flt-4) and to determine whether the presence of VEGF-D and Flt-4 was associated with the clinicopathologic characteristics and prognosis of pancreatic cancer. Methods: The expressions of VEGF-D and Flt-4 proteins were examined by immunohistochemical staining in 48 pancreatic cancer tissues, 32 adjacent pancreatic tissues, and 13 normal pancreatic tissue samples. Differences in distribution of VEGF-D or Flt4 were analyzed using the χ2 test. Kaplan-Meier survival analysis was used to estimate survival time and log-rank test was used to compare differences in survival time between the patients with or without VEGF-D or Flt-4 expression. Results: Immunohistochemical analysis revealed that the positive staining rates of VEGF-D and Flt-4 in pancreatic cancer tissues were significantly lower than that in para-cancerous tissues (P < 0.05), but significantly higher than that in normal pancreatic tissues (P < 0.05). Pancreatic cancer tissues with lymph node metastasis had higher expression of VEGF-D and Flt-4 compared with those without lymph node metastasis (P < 0.01). The median survival time and 1-, 2-, 3-year survival rate of VEGF-D-or Flt-4-positive patients were significantly decreased compared with VEGF-D- or Flt-4-negative patients (P < 0.05). Conclusion: VEGF-D and Flt-4 may contribute to lymph node metastasis and may serve as a prognostic factor for pancreatic cancer patients.