Rosuvastatin acts on the lymphatic system to improve atherosclerosis / 中华心血管病杂志

Objective: To investigate whether rosuvastatin acts on lymphatic system and influences lymphatic system-mediated reverse cholesterol transport to play an anti-atherosclerosis role. Methods: Forty-eight apolipoprotein E-/- mice fed a high fat diet were used to construct the atherosclerosis model. They were randomly divided into 4 groups with 12 rats in each group. They were treated with rosuvastatin, vascular endothelial growth factor-C (VEGF-C) and rosuvastatin+VEGF-C inhibitors as experimental group, and no intervention measures were given in control group. After 8 weeks, aortic plaque area, high density lipoprotein cholesterol (HDL-C) content in lymph fluid, the function of popliteal lymphatic drainage of peripheral Evans blue, and the ability of lymphatic system to transport peripheral cell membrane red fluorescent probes to label high-density lipoprotein (HDL) were detected. Subsequently, the effects of rosuvastatin on proliferation, migration and tubular function of lymphoendothelial cells and the expression of scavenger receptor class B type 1 (SR-B1) on lymphoendothelial cells at different concentrations were detected. Results: Compared with the control group, Rosuvastatin and VEGF-C could reduce the area of aortic atherosclerotic plaque (P<0.05). In addition to rosuvastatin plus VEGF-C inhibitor, the intra-aortic plaque area increased (P<0.05). Compared with the control group, Rosuvastatin could increase the content of HDL-C in lymphatic fluid (P<0.05), enhance the drainage function of lymphatic vessels, and enhance the capacity of HDL in the transport tissue fluid of lymphatic system. Compared with the control group, VEGF-C increased the content of HDL-C in mouse lymph fluid (P<0.01), enhanced the drainage function of popliteal lymphatic canal, and enhanced the ability of lymphatic system to transport HDL. With the addition of VEGF-C inhibitor on the basis of rosuvastatin, the content of HDL-C in lymph fluid was reduced, the drainage of popliteal lymphatic canal was interrupted, and the ability of lymphatic system to transport HDL was reduced. Western blotting showed that rosuvastatin increased the protein expression of SR-B1. Conclusion: Rosuvastatin can promote the proliferation, migration and tube formation of lymphatic endothelial cells. At the same time, SR-B1 expression on lymphatic endothelial cells is promoted, thus enhancing the lymphatic system mediated cholesterol reversal transport and playing the role of anti-atherosclerosis.

LncRNA AFAP1-AS1/miR-27b-3p/VEGF-C axis modulates stemness characteristics in cervical cancer cells / 中华医学杂志(英文版)

BACKGROUND@#Long non-coding RNA (lncRNA) actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs (miRs) to play cancer-promoting roles in cancer stem cells. However, the regulatory mechanism of AFAP1-AS1 in cervical cancer (CC) stem cells is unknown. The present study aimed to provide a new therapeutic target for the clinical treatment of CC.@*METHODS@#Hyaluronic acid receptor cluster of differentiation 44 variant exon 6 (CD44v6)(+) CC cells were isolated by flow cytometry (FCM). Small interfering RNAs of AFAP1-AS1 (siAFAP1-AS1) were transfected into the (CD44v6)(+) cells. The levels of AFAP1-AS1 were measured by quantitative real-time PCR (qRT-PCR). Sphere formation assay, cell cycle analysis, and Western blotting were used to detect the effect of siAFAP1-AS1. RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor (VEGF)-C.@*RESULTS@#CD44v6(+) CC cells had remarkable stemness and a high level of AFAP1-AS1. However, AFAP1-AS1 knockdown with siAFAP1-AS1 suppressed the cell cycle transition of G(1)/S phase and inhibited self-renewal of CD44v6(+) CC cells, the levels of the stemness markers octamer-binding transcription factor 4 (OCT4), osteopontin (OPN), and cluster of differentiation 133 (CD133), and the epithelial-mesenchymal transition (EMT)-related proteins Twist1, matrix metalloprotease (MMP)-9, and VEGF-C. In the mechanism study, miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+) CC cells.@*CONCLUSIONS@#LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.

Progress in the Mechanism of Lymphangiogenesis and Lymphatic Metastasis of Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer ranks the first cancer-related morbidity and mortality in China. Tumor metastasis always predicts the poor prognosis for patients. Moreover, lymphatic metastasis is one of the most significant predictors of poor prognosis in patients with non-small cell lung cancer (NSCLC) and lymphangiogenesis represents the bridge that functionally facilitates tumor lymphatic metastasis. In this review, we first discussed the molecular mechanisms of tumor-associated lymphangiogenesis and the interaction between tumor microenvironment and lymphatic endothelial cells, then, summarized the role of non-coding RNA in regulating tumor-associated lymphangiogenesis in recent frontier studies, with the aim to provide some novel insights on NSCLC-related lymphangiogenesis research, diagnosis and treatment.
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Association Between VEGF + 936 C> T Gene Polymorphism with Degrees of Neutrophils and Lymphocytes Infiltration in Gastritis

@#INTRODUCTION: Activation of angiogenesis stimulated by Vascular endothelial growth factor (VEGF) in host cells play a role in response to damaged gastric mucosal in gastritis patient with Helicobacter pylori (H. pylori) infection. The study showed that presence of polymorphisms in VEGF gene is associated with an increased risk of several disorders like gastric cancer. Infiltration of neutrophils in the gastric mucosa characterized acute gastritis. It can become chronic inflammation characterized by lymphocyte infiltration. This condition will complicate glandular atrophy and intestinal metaplasia in the gastric mucosal epithelium and subsequently cause gastric malignancy. The aim of this study to analyze association between VEGF +936 C>T polymorphism gene with degree of neutrophils and lymphocytes infiltration in gastritis patients with H. pylori. METHODS: Samples were obtained through consecutive sampling in April-August 2019. Gastritis was ensured by endoscopy while histological feature was defined by Sydney system. H. pylori was examined by Campylobacter Like Organism test (CLO) and VEGF + 936 C> T gene polymorphism was ensured using PCR TaqMan SNP Genotyping Assay rs2010963. Chi-square analysis was used in this study to determine the association between VEGF + 936 C>T gene polymorphism with degree of neutrophils and lymphocytes infiltration. RESULTS: Of 60 gastritis patients, there were CT genotype (37.5%), followed by CC genotypes (36.7%), and TT genotypes (35%). Patients with CC genotype increased the risk of 18 times moderate and severe neutrophil infiltration compared to CT+TT genotypes (p=0.001). There was no relationship between VEGF + 936 C>T polymorphism and the degree of lymphocytes infiltration (p=0.293) CONCLUSION: There was a significant association between VEGF + 936 C>T polymorphism and the degree of neutrophil infiltration but there was no association between VEGF + 936 C>T polymorphism and the degree of neutrophil infiltration.

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.

Association Between c-Met and Lymphangiogenic Factors in Patients With Colorectal Cancer

PURPOSE: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. METHODS: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed. RESULTS: Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found. CONCLUSION: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.

Benzodiazepine-Associated Carcinogenesis: Focus on Lorazepam-Associated Cancer Biomarker Changes in Overweight Individuals

OBJECTIVE: Cellular, animal, and human epidemiological studies suggested that benzodiazepines increase the risk of cancer and cancer mortality. Obesity is also clearly linked to carcinogenesis. However, no human studies have examined benzodiazepine-associated carcinogenesis as assessed by changes in cancer biomarkers. METHODS: A total of 19 patients were recruited, and received a 6-week treatment of 0.5 mg lorazepam. The measured cancer biomarkers were angiopoietin-2 (ANG-2), soluble CD40 ligand, epidermal growth factor, endoglin, soluble Fas ligand (sFASL), heparin-binding EGF-like growth factor (HB-EGF), insulin-like growth factor binding protein, interleukin (IL)-6, IL-8, IL-18, plasminogen activator inhibitor (PLGF), placental growth factor, transforming growth factor (TGF)-α, tumor necrosis factor (TNF)-α, urokinase-type plasminogen (uPA), vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D. RESULTS: Six cancer biomarkers were significantly increased in all patients as a whole. The subgroup analysis revealed a distinct pattern of change. Overweight patients showed a significant increase in 11 cancer biomarkers, including ANG-2, sFASL, HB-EGF, IL-8, PLGF, TGF-α, TNF-α, uPA, VEGF-A, VEGF-C, and VEGF-D. However, normal-weight patients did not show any changes in cancer biomarkers. CONCLUSION: Adiposity may have primed the carcinogenic potential, leading to lorazepam-associated carcinogenesis in overweight patients. Epidemiological studies addressing this issue should consider the potential modulator contributing to benzodiazepine-associated carcinogenesis.

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.

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.

The expression of Endophilin II and VEGF-C in human laryngeal cancer and connection with clinical treatment / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the expression of Endophilin II and VEGF-C in human Laryngeal cancer and its relationship with the clinical treatment effect.@*METHOD@#The expression and distribution of Endophilin II and VEGF-C protein were checked in 47 patients with laryngeal carcinoma in our hospital in 2006-09-2009-10 and 23 samples of normal tissues around the cancer by immunohistochemical staining SP method. After an appropriate surgical treatment, patients accepted a 5-year followup to evaluate their recurrence situation and 5-year survival rate.@*RESULT@#Immunohistochemistry showed that Endophilin II protein was strongly positive expressed in normal tissues around the cancer (positive rate 82.61%). And the expression level was dependent on the lymph metastasis, T stage and lymph invasion (P < 0.05). Patients with positive Endophilin II expression had a higher survival rate and better recurrence situation. Expression of VEGF-C was significantly higher in laryngeal carcinoma than in normal tissue around the cancer (positive rate 51.06% and 13.04%). the expression level was dependent on the lymph metastasis and lymph invasion (P < 0.05), and negatively correlated with recurrence and 5-year survival rate.@*CONCLUSION@#Endophilin II and VEGF-C may involve in laryngeal cancer, and the expression of Endophilin II and VEGF-C has a positive correlation with pathological features and lymph metastasis, and both are related with recurrence and 5-year survival rate. So these two proteins are likely to be a potential target for diagnosis and treatment of laryngeal cancer.

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.

Expression Levels of Vascular Endothelial Growth Factors A and C in Patients with Peptic Ulcers and Gastric Cancer

PURPOSE: Vascular endothelial growth factor (VEGF) is one of the most important growth factors for metastatic tumors. To clarify the role of VEGF-A and C in patients with peptic ulcer disease (PUD) or gastric cancer (GC), we evaluated the expression levels of these two molecules. We also analyzed the effect of Helicobacter pylori infection on VEGF-A and C expression levels. MATERIALS AND METHODS: Patients with dyspepsia who needed diagnostic endoscopy were selected and divided into three groups: non-ulcer dyspepsia (NUD), PUD, and GC, according to their endoscopic and histopathological results. Fifty-two patients with NUD, 50 with PUD, and 38 with GC were enrolled in this study. H. pylori infection was diagnosed by the rapid urease test. After RNA extraction and synthesis of cDNA, the expression levels of VEGF-A and C were determined by quantitative reverse transcriptase polymerase chain reaction. RESULTS: The VEGF-C expression level in the PUD and GC groups was significantly higher than that in the NUD group. Moreover, the VEGF-A expression level in the PUD and GC groups was higher than in the NUD group, although the differences were not statistically significant. Significant positive correlations were also observed between the expression levels of these two molecules in the PUD and GC groups. In addition, the expression levels of these two molecules were higher in H. pylori positive patients with PUD or GC than in H. pylori negative patients of the same groups; however, these differences did not reach statistical significance. CONCLUSIONS: Up-regulation of VEGF-C expression during gastric mucosal inflammation may play a role in the development of peptic ulcers or GC.

Protein and mRNA expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of leukemia patients and its correlation with clinical features / 中国实验血液学杂志

This study was aimed to investigate the mRNA and protein expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of patients with leukemia, and to analyze the role and clinical significance of these 4 factors in genesis and development of leukemia, infiltration and metastasis of leukemic cells. A total of 100 cases of newly diagnosed leukemia, 26 cases of acute leukemia in complete remission and 30 controls were enrolled in this study. The mononuclear cells of bone marrow were collected, the mRNA and protein expression levels of CTGF, CYR61, VEGF-C, VEGFR-2 in leukemia patients and controls were detected by real time PCR and Western blot, respectively. The results showed that the mRNA and protein expression levels of above mentioned 4 factors were significantly higher than those in control (P < 0.05), only CTGF mRNA expression in AL patients after complete remission showed statistical difference as compared with control (P < 0.05), but the expression of CTGF mRNA showed statistical significance in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF protein showed difference in different chromosome karyotypes of leukemia (P < 0.05). The expression levels of CYR61 and VEGF-C proteins showed statistical difference in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF, CYR61, VEGF-C mRNA and protein in CML group were higher than that in control group. The expression levels of CTGF and CYR61 protein were higher than that in control. The mRNA and protein expression levels of above-mentioned 4 factors in sex and infiltration lf leukemic cells did not show statistical significance(P < 0.05). In correlative analysis, the mRNA expressions of above mentioned 4 factors were positively correlated with bone marrow blast count(P < 0.05), the protein expression of CTGF, CYR61 and VEGF-C were positively correlated with bone marrow blast count. It is concluded that the CTGF, CYR61, VEGF-C and VEGFR-2 mRNA and protein play a role in acute leukemia. In acute leukemia (AML/ALL), the expression of above mentioned factor was high, but except VEGFR-2. Most of them were positively correlated with bone marrow blast count. Joint block of these angiogenesis-related factors is likely to play an important role in targeting treatment of leukemia.

Value of VEGF-C, VEGF-D and VEGFR-3 levels combined with serum TSH in diagnosis of papillary thyroid carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate serum vascular endothelial growth factor-C (VEGF-C), VEGF-D and VEGFR-3 levels in patients with papillary thyroid carcinoma (PTC) and analyze their relation with the clinicopathological and thyroid function of the patients.</p><p><b>METHODS</b>Serum samples and the data of thyroid function were collected from 55 patients with PTC and 24 with benign thyroid tumor (BT). ELISA was used to detect VEGF-C/D and VEGFR-3 concentration in the serum samples and their relation with the thyroid function was analyzed.</p><p><b>RESULTS</b>The VEGF-C and VEGFR-3 levels were significantly higher in PTC group than in BT group (P<0.05), but VEGF-D level was comparable between them (P>0.05). In PTC patients, the elevation of serum VEGF-C and VEGFR-3 levels was associated with an advanced clinical stage (III-IV), elevated thyroid-stimulating hormone (TSH) level, an age over 45 years, and a tumor diameter exceeding 2 cm (P<0.05 or P<0.01). Patients with lymph node metastasis had significantly higher VEGF-C level but lower VEGF-3 level than those without metastasis regardless of gender. Serum VEGF-D level was higher in PTC patients with lymph node metastasis (P<0.05) and elevated TSH level (P<0.01) without association with the clinical stage, tumor diameter, age, or gender. The area under ROC curve (AUC) of serum VEGF-C, VEGFR-3 and TSH was 0.803, 0.734 and 0.707 respectively (P<0.01), and that of VEGF-D was 0.556 (P>0.05); when combined, serum VEGF-C, VEGFR-3 and TSH showed an AUC of 0.862 (P<0.01).</p><p><b>CONCLUSION</b>Detecting serum VEGF-C and VEGFR-3 levels combined with TSH may enhance the early diagnosis rate of papillary thyroid carcinoma.</p>

Effect of Lymphangiogenic Factors on Survival in a Murine Model of Oral Squamous Cell Carcinoma

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.

Effect of vascular endothelial growth factor C and collagen triple helix repeat containing 1 expression on prognosis of rectal carcinoma patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the relationship of vascular endothelial growth factor C (VEGF-C) and collagen triple helix repeat containing 1 (CTHRC1) expression with the carcinogenesis and prognosis of rectal cancer.</p><p><b>METHODS</b>Cancer tissue samples from 120 rectal cancer patients confirmed by pathology in the People's Hospital of Yichun City from September 2005 to September 2010 were included in the study. Expressions of CTHRC1 and VEGF-C were examined by immunohistochemistry and their correlations with clinicopathological features and prognosis were analyzed.</p><p><b>RESULTS</b>The expression of VEGF-C was positively correlated with tumor size (r=0.943), TNM stages (r=0.784) and tumor differentiation (r=0.773) (all P<0.05). Similarly, the expression of CTRHC1 was also positively correlated with tumor size (r=0.829), TNM stages (r=0.632) and tumor differentiation (r=0.532) (all P<0.05). Rectal cancer patients with low expression of VEGF-C and CTHRC1 had significantly longer survival than those with high expression of VEGF-C and CTHRC1 [(40.0±1.3) vs. (35.4±0.5) months, P<0.01, (39.0±0.5) vs. (35.0±0.5) months, P=0.014].</p><p><b>CONCLUSION</b>VEGF-C and CTHRC1 may synergistically promote the invasion and metastasis of human rectal cancer, and provide evidence in predicting the prognosis of patients.</p>

STAT3, a Poor Survival Predicator, Is Associated with Lymph Node Metastasis from Breast Cancer / 한국유방암학회지

PURPOSE: The aim of this study is to explore signal transducer and activator of transcription 3 (STAT3) expression in breast cancer and to analyze the detailed mechanism that STAT3 contributes to the progression of breast cancer. METHODS: We retrospectively analyzed the clinicopathologic characteristics and overall survival (OS) of 140 breast cancer patients after curative surgery, and detected STAT3 expression, phosphorylated STAT3 (pSTAT3) expression, Ki-67 expression, vascular endothelial growth factor (VEGF)-C and -D expression in breast cancer tissues, and adjacent nontumor tissues. Survival analysis and relationship analysis were adopted for demonstrated the important mechanism of STAT3 contribution to progression of breast cancer. RESULTS: STAT3 expression, pSTAT3 expression, Ki-67 expression, VEGF-C expression, and VEGF-D expression in breast cancer tissues were significantly higher than those in adjacent nontumor tissues, respectively. With survival analysis, only number of lymph node metastasis (N stage) was identified as the independent predictors of the OS of breast cancer patients. Besides, we demonstrated there was the most prominent correlation between STAT3 expression and lymph node metastasis in breast cancer tissues by using the multinominal regression method. CONCLUSION: STAT3, a poor survival biomarker potential association with lymph node metastasis, was suitable for predication the OS of breast cancer patients after curative resection.

The VEGF signaling pathway in cancer: the road ahead / 癌症

The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF), play important roles in vascular biology in both normal physiology and pathology. The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab, also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target. Other members of the VEGF family are now being targeted, and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic. Here, we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.

Expression and clinical significance of vascular endothelial growth factor-C and nm23-H1 in stage II and III colorectal carcinomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To discuss the expression and clinical significance of VEGF-C and nm23-H1 in stage II and III colorectal carcinomas.</p><p><b>METHODS</b>SP immunohistochemical staining was employed to determine the expression of vascular endothelial growth factor-C (VEGF-C) and nm23-H1 in the tumor tissues of 110 cases of stage II and III colorectal carcinomas and in the adjacent mucosal tissues of 53 cases as control, and analyze their correlation with cliniopathological features and prognosis.</p><p><b>RESULTS</b>The positive expression of VEGF-C in the carcinoma tissues was 71.8%, significantly higher than that in the adjacent mucosal tissues (22.6%, P < 0.001). The positive expression of nm23-H1 in the carcinoma tissues was 57.3%, significantly lower than that in the adjacent mucosal tissues (90.6%, P < 0.001). The expression of VEGF-C was significantly correlated with lymph node metastasis (P < 0.05), and the nm23-H1 expression was significantly correlated with lymph node metastasis and pathological type (P < 0.05). The expression of VEGF-C and nm23-H1 did not show a significant correlation with age, gender, primary tumor site, tumor size and depth of invasion (P > 0.05). The VEGF-C expression was negatively related with nm23-H1 expression in colorectal carcinoma (r = -0.361, P < 0.001). The median overall survival (MOS) and median disease free survival (MDFS) of 110 patients with colorectal carcinoma were 55 and 48 months, respectively. The colorectal patients with different VEGF-C and nm23-H1 expression showed significant differences in the 5-year OS rate and 5-year DFS rate (P < 0.001). The patients with negative VEGF-C expression and positive nm23-H1 expression had a better prognosis.</p><p><b>CONCLUSIONS</b>The joint detection of VEGF-C and nm23-H1 expression is very promising in prediction of the prognosis of patients with stage II and III colorectal carcinoma. However, whether it can be used as a marker in prognosis judgment needs further investigation.</p>