Inhibitory Effects of Ligustrazine Plus Emodin on Expression of VEGF-related Factors in Ascites Carcinoma Walker-256 Cells / 中国实验方剂学杂志

Objective:To investigate the effects of ligustrazine combined with emodin on angiogenesis of ascites carcinoma Walker-256 cells by observing their inhibition against nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）， hypoxia-inducible factor-1<italic>α</italic> （HIF-1<italic>α</italic>）， and vascular endothelial growth factor-C （VEGF-C） in HIF signaling pathway. Method:Fifty SD rats were randomly divided into sham operation group， model group， ligustrazine group， emodin group and ligustrazine combined with emodin group. Following the in situ injection of rat ascites carcinoma Walker-256 cells into the liver of normal rats， they were grouped and administered with ligustrazine （10 mg·kg^-1）， emodin （10 mg·kg^-1）， and ligustrazine （10 mg·kg^-1） plus emodin （10 mg·kg^-1） for seven days. Afterwards， the tumor-inoculated liver tissue was sampled from the experimental group and prepared into pathological sections for investigating tumor cell survival and VEGF expression. The <italic>in vitro</italic> hypoxia and hypoglycemia model （oxygen-glucose deprivation model）， hypoxia model， and hypoglycemia model of Walker-256 cells were constructed respectively. In the ligustrazine group， emodin group， and ligustrazine combined with emodin group， three consecutive concentrations that did not affect the proliferation of Walker-256 cells were selected for investigation. The drugs were administered before modeling， and the model treatment lasted for 4 h. The levels of HIF-1<italic>α</italic>， VEGF-C， and NF-<italic>κ</italic>B in the cell culture supernatant of each group were tested. Result:After the rat liver was inoculated with Walker-256 cells， the total liver mass was significantly increased（<italic>P</italic><0.05）， higher than that in the ligustrazine group， the emodin group， or the ligustrazine combined with emodin group（<italic>P</italic><0.05）. Histopathological examination showed that the response of VEGF expression in the liver tissue of each administration group was lower than that of the model group. At the cellular level， the levels of HIF-1<italic>α</italic>， VEGF-C， and NF-<italic>κ</italic>B in oxygen-glucose deprivation model of the ligustrazine group and the ligustrazine combined with emodin group were significantly reduced（<italic>P</italic><0.05）， exhibiting a certain dose-dependent response， followed by the reduction in the hypoxia model. The levels of HIF-1<italic>α</italic> and NF-<italic>κ</italic>B in the oxygen-glucose deprivation model and the hypoglycemia model of the emodin（1×10^-2，1×10^-3 mol·L^-1） group and the ligustrazine combined with emodin（1×10^-2，1×10^-3 mol·L^-1） group were significantly reduced， but there was no significant change in VEGF-C level of the hypoxia model of all the administration groups. Conclusion:Ligustrazine or emodin alone or their combination inhibits the abnormal increase in the weight of rat liver after inoculation with Walker-256 cells and the expression of VEGF in the liver tissue. Ligustrazine and emodin inhibit the protein expression of NF-<italic>κ</italic>B and HIF-1<italic>α</italic>， thereby reducing the gene and protein expression of metastasis-related target VEGF-A activated by HIF-1<italic>α</italic> transcription， restricting tumor cell neovascularization， and inhibiting the invasion and spread of ascites carcinoma cells. Among them， ligustrazine has the most significant effect against hypoxia. Glucose interferes with the effect of ligustrazine. The combination of ligustrazine with emodin is conducive to diminishing the intervention of glucose and stabilizing the inhibition against tumor cells.

Changes of lymphatic vessel density in lung adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma and the regulatory factors / 南方医科大学学报

OBJECTIVE@#To analyze the changes in tumor lymphatic vessel density (LVD) in patients with lung adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA) and explore the regulatory factors of LVD.@*METHODS@#Complete clinicopathological data were collected form a total of 301 patients with lung adenocarcinoma, including 28 (9.3%) with AIS, 86 (28.6%) with MIA, and 187 (62.1%) with IA. The LVD of all the adenocarcinomas were calculated after D2-40 immunohistochemical staining, and MT1-MMP and VEGF-C expression levels were also evaluated. The differences in LVD among the groups and the correlations of tumor LVD with the expressions of MT1-MMP and VEGF-C and the clinicopathological factors were analyzed.@*RESULTS@#The LVD differed significantly among AIS, MIA, and IA groups (= 0.000). The LVDs was significantly correlated with the level of VEGF-C protein expression (=0.917, =0.009), tumor size (= 0.686, =0.017), lymph node metastasis (=0.739, =0.000), and clinical stage (=0.874, =0.012) of the patients.@*CONCLUSIONS@#Tumor lymphangiogenesis plays an important role in lung adenocarcinoma progression, and VEGF-C may promote this process.

Relationship between CNTN-1 and VEGF-C expression levels and recurrence, metastasis and prognosis of hepatocellular carcinoma patients after liver transplantation / 器官移植

Objective To investigate the relationship between contactin (CNTN)-1 and vascular endothelial growth factor (VEGF)-C expression levels and the recurrence,metastasis and prognosis of hepatocellular carcinoma(HCC) patients after liver transplantation.Methods Clinical data and pathological specimen of 105 patients diagnosed with primary HCC undergoing orthotopic liver transplantation were collected.The expression levels of CNTN-1 and VEGF-C in the cancerous and para-cancerous liver tissues were quantitatively measured by immunohistochemical staining.The relationship between the CNTN-1 and VEGF-C expression levels and clinicopathological characteristics,postoperative recurrence,metastasis and prognosis was statistically analyzed.Results The high expression rate of CNTN-1 and VEGF-C in liver cancerous tissues was 46.7％ and 39.0％,significantly higher compared with 11.4％ and 19.0％ in the para-cancerous tissues (both P＜0.05).Spearman correlation analysis revealed that the expression level of CNTN-1 was positively correlated with that of VEGF-C (P＜0.005).X2 test demonstrated that the expression of CNTN-1 protein was positively correlated with the level of alpha fetoprotein (AFP) (P=0.017),tumor,node,metastasis (TNM) staging(all P＜0.001),and negatively correlated with the degree of differentiation (P＜0.001).High expression of VEGF-C was positively correlated with TNM staging (P＜0.001).Cox multivariate analysis revealed that overall survival rate was significantly correlated with gender,AFP,degree of tumor differentiation,microvascular invasion,tumor diameter and high expression of CNTN-1 (P＜0.05-0.001).The recurrence-free survival was correlated with TNM staging,envelope integrity and high CNTN-1 expression (P＜0.05-0.001).Kaplan-Meier survival analysis revealed that postoperative overall survival curve and recurrence-free survival curve significantly differed between patients with high and low expression levels of CNTN-1 (both P＜0.01).Recurrence-free survival curve significantly differed between patients with high and low expression levels of VEGF-C (P=0.005).Conclusions CNTN-1 protein is highly expressed in HCC tissues and correlated with the expression of VEGF-C.It is associated with postoperative recurrence and metastasis of HCC after liver transplantation and affects the clinical prognosis of patients.

The effects of HIF-1α on the growth of transplanted oral cancer in nude mice and on the expression of CEACAM1 and VEGF-C in the tumor / 实用口腔医学杂志

Objective:To explore the effects of HIF-1α on the growth of transplanted oral cancer and on the expression of CEACAM1 and VEGF-C in the tumor.Methods:Nude mouse model of oral cancer was established by transplantation of Tca8113 cells respectively treated by HIF-1α siRNA and negative control siRNA subcutaneously into right axillary region of nude mice.3 weeks after transplantation the mice were sacrificed,the tumor volum and weight were measured.The tumor tissue was examined by ELISA method for the detection HIF-1α protein expression,by real-time quantitative PCR and western blot for the detection of mRNA and protein expression of HIF-1α,CEACAM1 and VEGF-C respectively.Results:The volume and weight of the transplanted tumor in HIF-1 α siRNA group were significantly less than those in the control group(P＜0.05),CEACAM1 and VEGF-C mRNA and protein were down-regulate in HIF-1α siRNA group (P＜0.05).Conclusion:HIF-1α expression is positively related to the expression of CEACAM1 and VEGF-C in the regulation of oral tumor growth.

Expressão de VEGF-C, VEGF-D, mensuração da densidade linfática e da proliferação endotelial linfática em neoplasias de glândulas salivar / Expression of VEGF-C, VEGF-D density measurement of lymphatic and lymphatic endothelial proliferation in salivary gland neoplasms

As neoplasias de glândulas salivares exibem uma grande diversidade morfológica e comportamentos biológicos variados o que suscita o interesse na pesquisa destas lesões. A disseminação das células tumorais é um passo inicial para a progressão de neoplasias malignas e, dentro deste contexto, os vasos linfáticos neoformados são considerados essenciais para que ocorra essa disseminação. O papel do VEGF (fator de crescimento endotelial vascular) na formação dos vasos é fato conhecido mas, pouco se sabe a respeito de sua participação em tumores de glândula salivar. Desta forma, o objetivo deste estudo foi avaliar a expressão do VEGF-C e VEGF-D, a densidade linfática tumoral (D2-40) e a proliferação endotelial linfática (dupla marcação D2-40/Ki-67) em uma série de neoplasias de glândulas salivares. A amostra foi composta por 20 adenomas pleomórficos, 20 carcinomas adenóides císticos, 20 carcinomas mucoepidermóides e 10 casos de tecido glandular salivar com características de normalidade para efeito comparativo. Todos os casos estudados exibiram expressão positiva para VEGF-C em região peritumoral e intratumoral, não sendo encontrada diferenças de imunoexpressão entre os grupos. No entanto, o grupo dos carcinomas adenóides císticos demonstrou diferença significativa da imunoexpressão do VEGF-C segundo o padrão cribriforme e sólido (p = 0,004). A maioria dos casos constantes do presente estudo, apresentou fraca marcação para VEGF-D em região peritumoral e intratumoral...

Salivary gland neoplasms exhibit a great morphological diversity and varied biological behavior which raises the interest in the study of these lesions. The spread of tumor cells is an early step in the progression of malignancies and the neoformed lymphatic vessels are considered essential in tumor dissemination. Vascular endotelial growth fator (VEGF) is a family of proteins involved in angiogenesis e lymphangiogenesis. However, in salivar tumors we have limited information on the expression. The aim of this study was to assess the expression of VEGF-C and VEGF-D, lymphatic vessel density (single-staining D2-40) and lymphatic endothelial proliferation (double labeling D2-40/Ki-67) in a series of salivary glands neoplasms. We selected 20 cases of pleomorphic adenoma, 20 of mucoepidermoide carcinoma, 20 of adenoid cystic carcinoma and 10 tissue sample of normal salivary gland. All cases studied showed positive expression of VEGF-C in intratumoral and peritumoral region, no differences in immunoreactivity was found between the groups. However, the group of adenoid cystic carcinoma showed a significant difference in immunoreactivity of VEGF-C by the cribriform and solid pattern (p = 0.004). Most of the cases included in this study showed weak immunoreactivity for VEGF-D in intratumoral and peritumoral region. In the assessment of lymphatic endotelial density peritumoral, intratumoral and total, the groups showed an increasing gradient, with lower values for the group of pleomorphic adenomas followed by mucoepidermoid carcinoma and adenoid cystic carcinoma. Lymphatic endothelial cell density was higher in malignant than benign tumors. No correlation was observed between the immunoreactivity of VEGF-C and VEGF-D in relation to tumor lymphatic density and lymphatic endothelial proliferation.

Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis

Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD.

Expression of Six1,TGF-βand VEGF-C in patients with laryngeal squamous cell carcinoma and their correlation analysis / 重庆医学

Objective To detect the expressions of Six1 ,TGF‐βand their common induced VEGF‐C in human laryngeal squa‐mous cell carcinoma ,and to explore their significance in the occurrence ,development ,metastasis and prognosis of laryngeal squa‐mous cell carcinoma .Methods The clinical data and preserved paraffin samples of 96 patients with laryngeal squamous cell carci‐noma confirmed by postoperative pathology were collected .The protein expression of Six1 ,TGF‐βand VEGF‐C was determined by adopting immunohistochemistry and Western blotting .Results The positive expression rates of Six1 ,TGF‐β and VEGF‐C in the laryngel squamous cell carcinoma tissue samples were 84 .4% (81/96) ,89 .6% (86/96)and 91 .7% (88/96)respectively .The positive expression rate of Six1 was significantly higher in the patients with poor differentiation and lymph node metastasis ;the positive ex‐pression rate of TGF‐βwas significantly higher in the patients with lymph node metastasis and had no relationship with the degree of differentiation ;the positive expression rate of VEGF‐C was significantly higher in the patients with poor differentiation and lymph node metastasis ;there was a positive correlation between expression of Six 1 and VEGF‐C in the laryngel squamous cell canc‐er tissue .Conclusion The high expression of Six1 ,TGF‐βand VEGF‐C may promote lymphatic metastasis of laryngeal squamous cell carcinoma .Six1 expression may be one of the important influencing factors of the expression change of VEGF‐C .The combined detection of Six1 ,TGF‐βand VEGF‐C has an important clinical significance for judging the metastasis and prognosis of LSCC .

Value of combined detection of CA125 and VEGF-C,β2-MG in early diagnosis of ovarian cancer lymph node metastasis / 国际检验医学杂志

Objective To investigate the value of combined detection of serum CA125 ,VEGF‐C andβ2‐MG levels on early diag‐nosis of retroperitoneal lymph node metastasis in the patients with ovarian cancer .Methods Fifty‐one patients with ovarian cancer undergoing retroperitoneal lymph node cleaning operation were included as the experimental group ,including 29 cases of positive retroperitoneal lymph node metastasis .Contemporaneous 32 cases of benign ovarian tumor were selected as the control group .The serum CA125 level was detected by using electricity chemiluminescence (electrocheminescence) ,serum VEGF‐C level by using en‐zyme‐linked immunosorbent assay (ELISA) and serumβ2‐MG level by using the latex enhanced immune turbidimetric method .The serum CA125 ,VEGF‐C andβ2‐MG levels were compared among various groups .Results The serum CA125 ,VEGF‐C andβ2‐MG levels in the experimental group were (1 682 .5 ± 261 .5)μg/mL ,(2 125 .6 ± 96 .7)pg/mL and (2 .52 ± 0 .61)mg/L respectively , which in the control group were (30 .5 ± 6 .3)μg/mL ,(1 738 .0 ± 79 .8)pg/mL and (1 .87 ± 0 .56)mg/L respectively ,the difference between them was statistically significant (P< 0 .01) .The serum CA125、VEGF‐C、β2‐MG levels in 29 cases of retroperitoneal lymph node metastasis were more significantly higher ,which were (1 997 .3 ± 376 .8)μg/mL ,(2 895 .2 ± 126 .8)pg/mL and (4 .95 ± 0 .69)mg/L respectively ,and the difference was statistically significant compared with the control group (P<0 .01) .The sensitivity ,specificity and accuracy rate of the combined detection of serum VEGF‐C ,β2‐MG and CA125 for diagnosing ovarian cancer retroperitoneal lymph node metastasis were 95 .8% ,97 .3% and 98 .5% respectively .Conclusion The combined detection of serum VEFG‐C ,β2‐MG and CA125 has an important clinical value in early diagnosing retroperitoneal lymph node metastasis of o‐varian cancer .

Study on correlation between VEGF level and malignant pleural effusion / 中国生化药物杂志

Objective Methods To explore the value of VEGF levels in serum and pleural effusion for diagnosis of benign and malignant tumors, and evaluate clinical value of VEGF-A, C, D in malignant pleural effusion.Methods Serum and pleural effusion of 34 cases patients with lung cancer were collected in our hospital, the application of ELISA method for the detection of VEGF level in serum and pleural effusion in patients with lung cancer and with benign pleural effusion.VEGF-A, C, D levels were detected.Results VEGF levels in serum and pleural effusion in malignant group were significantly higher than those in benign group(P<0.05).In addition, patients with lung cancer before initial treatment, the VEGF levels in serum and pleural effusion of distant metastasis group were significantly higher than those of without distant metastasis group(P<0.05).There was a correlation between the level of VEGF and the malignant pleural effusion(r=0.878, P<0.05).No correlation existed between VEGF level and benign pleural effusion.The content of sVEGF-A in serum had no statistical difference in cancer group and benign group.Effusion supernatants of pVEGF-A content in lung cancer group were higher than those in benign effusion group(P<0.05).pVEGF-A and sVEGF-A levels were similar in benign effusion group. Effusion supernatants pVEGF-A in malignant group was higher than that in benign effusion group(P<0.05).pVEGF-A was significantly higher than that of sVEGF-A in malignant effusion(P<0.05).Serum VEGF-C, VEGF-D content had no significant difference between cancer group and benign group. pVEGF-C, pVEGF-D content had no significant difference between cancer group and benign group.Conclusion Level of VEGF in serum and pleural effusion detection would help to diagnose and differentially diagnose benign and malignant pleural effusion.Effusion VEGF-A is different in benign and malignant effusion, which may become benign and malignant effusion tumor markers.

The clinic significance of TIP30 and VEGF-C protein expressions in small cell lung cancer / 实用肿瘤学杂志

Objective To investigate the correlation between TIP 30 and VEGF-C expression and clini-cophathological characteristics in resected small cell lung cancer ( SCLC) patients and to identify patients with in-creased risk of cancer recurrence and to provide a theoretical basis for the further clinical prevention of SCLC . Methods Sixty eight resected SCLC patients were included in this study .Paraffin-embedded specimens of pa-tients were used for the evaluation of TIP 30 and VEGF-C expression by immunohistochemistry .Results The expression of VEGF-C had positive correlation with lymph node metastasis .TIP30 expression was positively cor-related with VEGF-C expression.Patients with low TIP30 expression had shorter Overall survival (OS)and Dis-ease-Free survival(DFS)than those with high TIP30 expression.OS and DFS of the patients with VEGF -C-positive tumors were significantly lower than that of the patients with VEGF -C negative tumors .The multivariate Cox regression analysis showed that low TIP 30 and high VEGF-C expression were independent markers of poor OS(P<0.01)in operable SCLC patients.Conclusion The expression of VEGF -C shows positive correlation with lymph node metastasis .Low TIP30 and high VEGF -C expression are independent prognostic markers of poor overall survival in resected SCLC patients .

Study on effect of anthracyclines on VEGF-C, VEGFR-3, ER and E-cadherin in serum of patients with breast cancer / 中国生化药物杂志

Objective To investigate effect of anthracyclines of VEGF-C, VEGFR-3, ER and E-cadherin in serum of patients with breast cancer.Methods 43 patients with breast cancer were selected and randomly divided into experimental group and control group, 40 cases in each group.According to the experimental program based on the treatment, serum VEGF-C, VEGFR-3 levels and breast tissue ER and E-cadherin were detected after the end of the treatment.Results Compared with the control group, VEGF-C, VEGFR-3 levels of the experiment group were lower( P<0.05),ER level was lower(P<0.05) and E-cadherin level was higher(P<0.05).Conclusion the ER, VEGFR-3 and VEGF-C levels in breast cancer patients can significantly decrease the E-cadherin level, and it has a guiding significance for clinical.

DNA methylation regulates expression of VEGF-C, and S-adenosylmethionine is effective for VEGF-C methylation and for inhibiting cancer growth

DNA hypomethylation may activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-adenosylmethionine (SAM) is a methyl donor in numerous methylation reactions and acts as an inhibitor of intracellular demethylase activity, which results in hypermethylation of DNA. The main objectives of this study were to determine whether DNA hypomethylation correlated with vascular endothelial growth factor-C (VEGF-C) expression, and the effect of SAM on VEGF-C methylation and gastric cancer growth inhibition. VEGF-C expression was assayed by Western blotting and RT-qPCR in gastric cancer cells, and by immunohistochemistry in tumor xenografts. VEGF-C methylation was assayed by bisulfite DNA sequencing. The effect of SAM on cell apoptosis was assayed by flow cytometry analyses and its effect on cancer growth was assessed in nude mice. The VEGF-C promoters of MGC-803, BGC-823, and SGC-7901 gastric cancer cells, which normally express VEGF-C, were nearly unmethylated. After SAM treatment, the VEGF-C promoters in these cells were highly methylated and VEGF-C expression was downregulated. SAM also significantly inhibited tumor growth in vitro and in vivo. DNA methylation regulates expression of VEGF-C. SAM can effectively induce VEGF-C methylation, reduce the expression of VEGF-C, and inhibit tumor growth. SAM has potential as a drug therapy to silence oncogenes and block the progression of gastric cancer.

Syk and VEGF-C in breast cancer's expression with lymph node metastasis / 中国免疫学杂志

Objective:To explore the relationship of Syk and VEGF-C expression in breast cancer with lymph node metastasis . Methods:The expression of Syk and VEGF-C in 40 cases of breast cancer were determined using immunohistochemistry assay .Then, the positive rates of Syk and VEGF-C were compared with lymph node metastasis .Results:The expression rate of VEGF-C and Syk in breast cancer was respectively 77.5%(31/40), 37.5%(15/40).VEGF-C protein expression was not significant related with the tumor diameter (P>0.05) and histological grade (P>0.05), but was significantly associated with lymph node metastasis (P0.05) and the histological grade(P>0.05), and was associated with lymph node metastasis (P<0.05).The difference of Syk and VEGF-C had statistics significance(P<0.05).Con-clusion:Syk and VEGF-C involved in the lymphatic invasion and metastasis , may be an important indicator of prognosis .

The influence of HGF on the expression of VEGF-C and its mechanism in human tongue squamous cell carcinoma Tca8113 cells / 实用口腔医学杂志

Objective:To investigate the influence of hepatocyte growth factor(HGF)on the expression of vascular endothelial growth factor C(VEGF-C)and the mechanism of HGF-induced VEGF-C expression in tongue squamous cell carcinoma Tca8113 cells.Methods:Tca8113 cells were cultured and exposed to HGF with various concentrations.The expression level of VEGF-C was assessed by ELISA.Signaling transduction inhibitors LY294002,U0126,SP600125,SB203580 was used to block PI3K/Akt,P44 /P22MAPK,JNK,P38MAPK signaling pathways,respectively.Then,the expression level of VEGF-C was detected by ELISA.Re-sults:The VEGF-C expression of Tca8113 cells increased at the beginning and decreased later with the increase of HGF concentra-tion.When the concentration of HGF was 40 ng/ml,VEGF-C expression level was the highest.Inhibitor LY294002 of PI3K/Akt and Inhibitor U0126 of P44 /P22MAPK significantly blocked the effects on HGF-induced VEGF-C up-regulation(P ＜0.01 ).Inhibitor SP600125 of JNK and inhibitor SB203580 of P38MAPK didn't interfere HGF-induced VEGF-C expression(P >0.05).Conclusion:HGF contributed to the expression of VEGF-C,PI3K/Akt and P44 /P22MAPK signaling pathways may be involved in HGF-induced VEGF-C up-regulation,and may play potential roles in lymphatic metastasis of oral squamous cell carcinoma.

Preliminary study on the expression and clinicopathological significance of VEGF-C mRNA in prostate cancer / 医学研究生学报

Objective Prostate cancer is one of the most common cancer in males .The article was to investigate the expres-sion and clinicopathological significance of VEGF-C mRNA in prostate cancer , finding the molecular marker for early diagnosis and prognosis assessment of prostate cancer . Methods TaqMan real-time polymerase chain reaction ( PCR) analysis was used to detect the expression of VEGF-C mRNA in 3 prostate cancer cell lines(PC-3, DU145 and LNCap), 32 cases of prostate cancer (Pca) sam-ples and 15 cases of benign prostatic hyperplasia (BPH).Analysis was also made on the correlations of VEGF-C mRNA expression, clinicopathological features and prognosis . Results High levels of VEGF-C mRNA were detected in PC-3 ( 153 .31 ±26 .24 ) and DU145(194.62 ±41.36)compared to LNcap(1.00 ±0.00).The expression of VEGF-C mRNA in prostate cancer tissues was 3.43 folds higher than that in the benign prostatic hyperplasia tissues ([13.67 ±1.95] vs [11.89 ±1.63], P=0.004).The high expres-sion of VEGF-C mRNA in prostate cancer was associated with high Gleason score ( P =0.004 ) and lymph node metastasis ( P =0.015).In patients with high expression and low expression of VEGF-C mRNA, the 3-year survival rate was 12.5%and 40.0%re-spectively(P=0.033). Conclusion The VEGF-C mRNA expression may be related to the biological behavior of prostate cancer .It is suggested that VEGF-C mRNA can be used as a prognostic marker for prostate cancer .

Specific MR imaging of hepatocellular carcinoma with VEGF-C targeted USPIO probe in a rat model / 实用放射学杂志

Objective To investigate the potential value of VEGF-C targeted ultrasmall superparamagnetic particles of iron oxide (USPIO)molecular probe in specific detection of hepatocellular carcinoma (HCC)in a rat model using MRI.Methods The targeted probe was synthesized by conjugating VEGF-C antibody with amino modified USPIO.Cell counting kit-8 assay was conducted to as-certain the probe’s effect on the growth of HepG2 cells.Rat models with HCC were divided into two groups (targeted group with VEGF-C-USPlO and a contrast with USPIO)with 3 rats for each group at random.Pre-and post-contrast enhanced MR imaging with different time points of 0.5,1 and 1.5h was performed with an injection into caudal vein.The signal intensities of the tumor on T2 WI and T2 * WI were measured,and the differences of the signal intensities between pre-and post-enhancements or between both groups were analyzed.The iron particles within the tumors in two groups were confirmed by Prussian blue iron staining.The ex-pression of VEGF-C in HCC was proved by immunohistochemistry.Results The signal intensities of HCC on T2 WI and T2 * WI af-ter VEGF-C-USPI0 injection were decreased obviously with a minimum value at 1 h ,indicating a significant difference (P 0.05).Statistical differences in signal inten-sity on T2 * WI after enhancement between both groups were also showed (P <0.05).Prussian blue staining results showed more iron particles within the tumor tissues in VEGF-C-USPI0 group,whereas less ones in USPIO group.Immunohistochemical results showed that VEGF-C was over expressed in cytoplasm and membrane.Conclusion VEGF-C-USPI0 molecular probes can initiatively target to the liver cancer in rat models with expressed VEGF-C,which may help to achieve the specific MR imaging of HCC,indica-ting a potential of the metastasis.

Decreased serum level and increased urinary excretion of vascular endothelial growth factor-C in patients with chronic kidney disease

BACKGROUND: Interstitial tonicity increases vascular endothelial growth factor-C (VEGF-C), a lymphangiogenic factor in salt-induced hypertension. Therefore, it can be assumed that changes of serum VEGF-C level may be associated with increasing blood pressure. However, there is no report about the changes of serum VEGF-C levels in patients with chronic kidney disease (CKD). The aims of this study were to investigate the changes of serum and urine VEGF-C levels in patients with CKD stage 3-4 and to evaluate the relationship between blood pressure and serum VEGF-C levels in the patients with CKD stage 5 and hemodialysis. METHODS: Glomerular filtration rate (GFR) was assessed by the Modification of Diet in Renal Disease equation. Blood pressure and VEGF-C levels (serum and urine) were measured by enzyme-linked immunosorbent assay (ELISA) in nine patients with stage 3-4 CKD, 41 hemodialysis patients, and eight healthy individuals. RESULTS: The median serum level of VEGF-C in patients with stage 3-4 CKD and stage 5 hemodialysis significantly decreased in comparison with healthy individuals. Urinary VEGF-C excretion increased in patients with stage 3-4 CKD compared with healthy control patients. For 41 hemodialysis patients, the serum level of VEGF-C in patients with stage 1 or stage 2 hypertension with hemodialysis did not significantly increase when compared with prehypertension hemodialysis patients. CONCLUSION: We demonstrated that circulating levels of VEGF-C were decreased in patients with CKD, and the decrease of VEGF-C in patients with stage 3-4 CKD coincided with an increase in the urinary excretion of VEGF-C.

Expression of Kiss-1, Ki-67 and VEGF-C in papillary thyroid carcinoma and its stereological determination / 军事医学

Objective To explore the expression and significance of Kiss-1, Ki-67 and VEGF-C in papillary thyroid carcinoma(PTC) and thyroid follicular adenoma (FA).Methods Forty-four cases of PTC and twelve cases of FA paraffin-embedded tissues were used .Immunohistochemical staining and microscopic image analysis technique were used to analyze the expression of Kiss-1, Ki-67 and VEGF-C.Results The integrated optical density (IOD) of Kiss-1, and VEGF-C in the PTC groups was 475.56 ±126.02 and 805.29 ±226.05,respectively.The proliferation index of Ki-67 protein was (3.36 ±1.11) %and the difference between the PTC and FA groups was statistically significant (P<0.05).The IOD of the above two indices was 408.12 ±124.05 and 912.63 ±108.12 in the PTC with lymph node metastasis group , respectively, while the proliferation index of Ki -67 protein was (3.93 ±0.92) % and the difference vs the group without lymph node metastasis was significant ( P <0.05 ) .In the PTC with capsular infiltration group the IOD of above two was 425.58 ±87.38 and 891.37 ±149.36, the proliferation index of Ki -67 protein was (3.79 ±1.09) %and the difference with PTC group without capsular infiltrtion was statistically significant (P<0.05).Linear correlation analysis showed that Ki-67 and VEGF-C were with positively correlated in PTC and FA tissues (P<0.05),while Kiss-1 and Ki-67, VEGF-C were with negatively correlated in PTC and FA tissues (P<0.05).Conclusion Kiss-1, Ki-67 and VEGF-C can facilitate the differential diagnosis of PTC and FA , serving as prognostic indicators in patients with PTC .

Relationships between Lymph Node Metastasis and Expression of CD31, D2-40, and Vascular Endothelial Growth Factors A and C in Papillary Thyroid Cancer

OBJECTIVES: To investigate the relationships between lymph node metastasis (LNM) and expression of CD31, D2-40 and vascular endothelial growth factors (VEGF)-A and -C in patients with papillary thyroid cancer (PTC). METHODS: Paraffin-embedded thyroid tissues of 72 patients were evaluated, which included 25 patients with thyroid nodular hyperplasia (TNH), 24 PTC patients without LNM, and 23 PTC patients with LNM. Three pathologists, who were blinded to the patient's clinical information, assessed the immunohistochemical staining results. The amount of expression was scored as high (>25% of cells stained) or low (0-25%). RESULTS: A higher level of VEGF-A expression was observed in the PTC groups regardless of LNM when compared to the group with TNH (91.3%, 79.2%, 4.0%, respectively). VEGF-C expression in the PTC with LNM group was significantly higher than the other two groups (P<0.05). No difference in microvessel density (MVD) scores was observed using CD31 among the three groups. The lymphatic vessel density (LVD) score using D2-40 was significantly higher in patients having PTC with LNM than the other groups (P<0.05). CONCLUSION: VEGF-C and D2-40 were more highly expressed in patients having PTC with LNM than in patients having PTC without LNM or in those having TNH. Analysis of VEGF-C level and LVD using D2-40 may be helpful in the diagnosis of PTC and the evaluation of LNM potential in patients with PTC.

VEGF-C facilitates development of esophageal squamous cancer via regulating expression of CNTN-1 / 中华消化内镜杂志

ObjectiveTo investigate the biological significance and mechanism of VEGF-C in esophageal tumor development,and correlation of CNTN-1 level with VEGF-C.MethodsThe expression of VEGF-C and its receptors in esophageal squamous cancer cell (ESCC) and in corresponding noncancerous esophageal tissue specimens were detected by real-tithe PCR.Esophageal squamous cancer cell line TE-1 was transinfected by VEGF-C overexpression and gene silencing vectors,respectively,and the relative amount of C/EBP bound to CNTN-1 promoter was determined by quantitative ChIP,to explore the possibility that VEGF-C was involved in development of esophageal cancer through mediating transcription of CNTN-1.ResultsThe mRNA levels of VEGF-C was significantly higher in ESCC than in normal esophageal tissues.VEGF-C expression was significantly increased in VEGF-C-overexpressing TE-1 cells compared to untransfected cells (mock).Cells transfected with either of the VEGF-C targeting shRNA vectors,shRNA-1 and shRNA-2,showed reduced VEGF-C transcripts (P ＜ 0.01 ).Expression levels of VEGF-C and CNTN-1 mRNA correlated significantly with each other.The binding site of C/EBP in CNTN-1 was detected by ChIP,and the relative amount of C/EBP binding to CNTN-1 promoter was significantly increased in TE-1 after transfecting by VEGF-C overexpression vector ( P ＜ 0.05).ConclusionVEGF-C and its receptor are highly expressed in esophageal cancer tissues,which may be associated with ESCC carcinogenesis and development.VEGF-C may influence on growth and migration in TE-1 cells through CNTN-1.