Vascular Endothelial Growth Factor In Peripheral Blood Research Articles

Involvement of stromal cell-derived factor-1α (SDF-1α), stem cell factor (SCF), fractalkine (FKN) and VEGF in TSG protection against intimal hyperplasia in rat balloon injury

BackgroundIntimal hyperplasia is the major therapeutic concern after percutaneous coronary intervention. The aim of this study is to investigate effects of 2,3,4′,5-tetrahydroxystilbene-2-O-β-D glucoside (TSG) on intimal hyperplasia and the underling mechanisms through attenuating the expressions of stromal cell-derived factor-1α (SDF-1α)/CXCR4, stem cell factor (SCF)/c-kit and fractalkine (FKN)/CX3CR1, and through promoting re-endothelialization with vascular endothelial growth factor (VEGF). MethodRats were operated with carotid artery balloon injury. The treatment groups were gavaged with 50 and 100 mg/kg/d of TSG. After 10 days of treatment, carotid artery pathological changes were evaluated by histology. Serum levels of SDF-1α, SCF, FKN and VEGF were detected by enzyme linked immunosorbent assay. The protein expressions of the receptors c-kit, CXCR4, CX3CR1, as well as CD34 and proliferating cell nuclear antigen (PCNA) were detected by immunochemistry. ResultsTSG dose-dependently inhibited balloon injury-induced intimal hyperplasia, as evidenced by reducing neointima area (NIA), neointima area/media area (NIA/MA), neointima area/internal elastic area (NIA/IELA), and by decreasing the protein expression of PCNA. TSG reduced serum levels of SDF-1α, SCF and FKN, and it also decreased the expressions of the corresponding receptors c-kit, CXCR4, CX3CR1 in neointima. Importantly, the level of VEGF in peripheral blood and the expression of CD34 in vascular walls were increased to promote re-endothelialization. ConclusionsThis study clearly demonstrated that TSG was effective in inhibiting intimal hyperplasia, and this effect was mediated, at least in part, through the SCF/c-kit, SDF-1α/CXCR4 and FKN/CX3CR1 axes. Importantly, TSG could increase VEGF and CD34 to promote endothelial repair.

Expression differences and analysis of Endostatin and VEGF in different efficacy NSCLC patients treated with rh-endostatin combined chemotherapy

Objective To investigate the clinical significance and difference in the expression of endostatin and vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC) patients with different response to recombinant human endostatin (rh-endostatin) combined with chemotherapy. Methods Serum levels of endostatin and VEGF in peripheral blood of 30 patients with stage Ⅳ NSCLC (NSCLC group) and 30 healthy controls (control group) were determined by enzyme-linked immunosorbent assay. Two cycles of chemotherapy combined with rh-endostatin were provided to NSCLC patients to evaluate the efficacy of the regimen. Simultaneously, serum levels of endostatin and VEGF were measured before and after treatment. Results The level of serum endostatin was (37.96±9.01)ng/ml and (40.12±12.11)ng/ml in NSCLC patients and healthy controls, respectively, which was lower in the former than that of the latter, without statistical difference (P>0.05). Furthermore, the level of serum VEGF was (127.98 ±33.88)pg/ml and (36.33±15.43)pg/ml in NSCLC patients and healthy controls, respectively, which was higher in the former than that of the latter, with statistical difference (t=13.48, P 0.05). After two cycles of chemotherapy combined with rh-endostatin treatment, the level of serum endostatin in partial response (PR) or stable disease (SD) patients was (76.22±20.41)ng/ml, higher than that of progressive disease (PD) patients, which was (31.24±13.09)ng/ml (t=7.143, P<0.05). In addition, the level of serum VEGF in PR or SD patients was (93.28±21.33)pg/ml, which was lower than (155.81±48.38)pg/ml of the PD patients (t=3.503, P<0.05). Conclusions The levels of endostatin and VEGF are associated with the efficacy of anti-angiogenesis combined with chemotherapy in NSCLC patients. Key words: Carcinoma, non-small-cell lung/DT; Antineoplastic combined chemotherapy protocols/TU; Endostar/AD; Endostatins/ME; Vascular endothelial growth factors/ME

Effect of ranibizumab on levels of IL-6 and VEGF in peripheral blood and aqueous humor of glaucoma rat model and association of IL-6 and VEGF with optic nerve damage.

This study aims to investigate the effect of intravitreal injection of ranibizumab on glaucoma rat model and its effect on optic nerve injury. A total of 125 SD rats were used to establish glaucoma models. Of them, 80 well-established model were selected, 40 of which received intravitreal injections of ranibizumab and were assigned to the observation group. The remaining 40 received no drug and were assigned to the control group. After rats were sacrificed at the time-points, the retina was harvested. Numbers of retinal ganglion cells (RGCs) were counted under a fluorescence microscope. In the meantime, levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in peripheral blood and aqueous humor were determined. The levels of IL-6 and VEGF in peripheral blood and aqueous humor decreased gradually over the time of treatment in the observation group (P<0.05). In the control group the levels of IL-6 in peripheral blood and aqueous humor increased gradually over time (P<0.05). At the same time-point, the IL-6 level was higher in the control group than that in the observation group (P<0.05). The VEGF level in the observation group was lower in day 21 than that in day 7 (P<0.05). The VEGF level was higher in the control group than that in the observation group (P<0.05). The number of RGCs in the observation group increased gradually over the time of treatment, and there were significant differences in the number of RGCs between day 7 and 14, as well as day 14 and 21 (P<0.05). The number of RGCs in the control group decreased gradually over time (P<0.05). The levels of IL-6 and VEGF were all negatively correlated with the number of RGCs, and the correlation coefficient r and P-value were −0.743 and 0.012, and −0.675 and 0.022, respectively. Ranibizumab attenuated optic nerve injury by reducing levels of IL-6 and VEGF in peripheral blood and aqueous humor of glaucoma rat model.

Chemotherapy regimen based on sorafenib combined with 5-FU on HIF-1α and VEGF expression and survival in advanced gastric cancer patients.

The present study investigated the effect of combined sorafenib chemotherapy on hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression and survival time of patients with advanced gastric cancer. From January 2010 to December 2011, 92 patients diagnosed with advanced gastric cancer were selected and randomly divided into the treatment group and control group. The treatment group was treated with sorafenib chemotherapy combined with 5-fluorouracil (5-FU), and the control group received 5-FU. The treatment course was 3–4 cycles. During the same period, 46 healthy persons admitted to the Second People's Hospital of Huaian were selected as the controls. A volume of 3–4 ml peripheral blood from each patient and control was collected before and after treatment. The expression levels of HIF-1α and VEGF in peripheral blood were measured by ELISA. The survival time of patients with advanced gastric cancer was followed and analyzed. Compared with healthy controls, serum levels of HIF-1α and VEGF were significantly higher in patients with advanced gastric cancer (P<0.05). After chemotherapy combined with sorafenib, the peripheral blood levels of HIF-1α and VEGF decreased significantly in the treatment group (P<0.05). The 5-year survival rate of patients in the two groups was followed. Compared with the control group, the 1-year survival rate of the treatment group was significantly higher (P<0.05). In conclusion, chemotherapy combined with sorafenib can effectively reduce serum levels of HIF-1α and VEGF in patients with advanced gastric cancer, and improve their 1-year survival rate and prognosis. Therefore, it has significant clinical application value.

The current status of tailor-made medicine with molecular biomarkers for patients with clear cell renal cell carcinoma

Appropriate use of multiple reliable molecular biomarkers in the right context will play a role in tailormade medicine of clear cell renal cell carcinoma (RCC) patients in the future. A total of 11,056 patients from 53 studies were included in this review. The article numbers of the each evidence levels, using the grading system defined by the Oxford Centre for Evidence-based Medicine, in 1b, 2a, 2b, and 3b were 5 (9%), 18 (34%), 29 (55%), and 1 (2%), respectively. The main goal of using biomarkers is to refine predictions of tumor progression, pharmacotherapy responsiveness, and cancer-specific and/or overall survival. Currently, carbonic anhydrase (CA9) and vascular endothelial growth factor (VEGF) in peripheral blood and p53 in tumor tissues are measured to predict metastasis, while VEGF-related proteins in peripheral blood are used to assess pharmacotherapy responsiveness with sunitinib. Furthermore, interleukin 8, osteopontin, hepatocyte growth factor, and tissue inhibitors of metalloproteinases-1 in peripheral blood enable assessment of responsiveness to pazopanib treatment. Other reliable molecular biomarkers include von Hippel–Lindau gene alteration, hypoxia-inducible factor-1a, CA9, and survivin in tumor tissues and VEGF in peripheral blood for predicting cancer-specific survival. In the future, studies should undergo external validation for developing tailored management of clear cell RCC with molecular biomarkers, since individual institutional studies lack the generalization and consistency required to maintain accuracy among different patient series.

Predictive value of preoperative serum CCL2, CCL18, and VEGF for the patients with gastric cancer

BackgroundTo investigate the expression of chemokine ligand 2 (CCL2), chemokine ligand 18 (CCL18), and vascular endothelial growth factor (VEGF) in peripheral blood of patients with gastric cancer and their correlation with presence of malignancy and disease progression.MethodsSixty patients with pathological proved gastric cancer were prospectively included into study. The levels of CCL2, CCL18, and VEGF in peripheral blood were examined by enzyme-linked immunosorbentassay (ELISA). Peripheral blood from 20 healthy people was examined as control.ResultsThe preoperative serum levels of CCL2, CCL18 and VEGF in gastric cancer patients were significantly higher than that of controls (P <0.001, P <0.001, and P <0.001, respectively). ROC curve analysis showed that with a cut-off value of ≥1272.8, the VEGF*CCL2 predicted the presence of gastric cancer with 83% sensitivity and 80% specificity. Preoperative serum CCL2 was significantly correlated to N stage (P =0.040); CCL18 associated with N stage (P =0.002), and TNM stage (P =0.002); VEGF correlated to T stage (P =0.000), N stage (P =0.015), and TNM stage (P =0.000).ConclusionPreoperative serum levels of CCL2 and VEGF could play a crucial role in predicting the presence and progression of gastric cancer.

Effect of electro-acupuncture on tumor necrosis factor-α and vascular endothelial growth factor in peripheral blood and joint synovia of patients with rheumatoid arthritis

To observe the effect of electro-acupuncture (EA) on tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in peripheral blood and joint synovia in patients with rheumatoid arthritis (RA) to verify the clinical efficacy of EA. Adopting randomized controlled principle, the 63 RA patients enrolled were assigned to two groups, the 32 patients in the EA group were treated with EA, and the 31 patients in the simple needling (SN) group treated with simple needling. According to the integral-local combining method, the acupoints were selected mainly from yang-meridian and local Ashi points (pain-point). EA or SN was applied every other day, 10 times as a course, and each patient received a total of 3 courses of treatment. Blood and synovial levels of TNF-α and VEGF were reduced significantly after treatment in both groups. The lowering (absolute value and difference value) of TNF-α as well as the absolute value of VEGF, either in blood or in synovia, were similar in the two groups (P>0.05); but the lowering of VEGF after treatment was more significant in the EA group than that in the SN group (P<0.05). EA could effectively lower the contents of TNF-α and VEGF in peripheral blood and joint synovia to improve the internal environment for genesis and development of RA, so as to enhance the clinical therapeutic effectiveness.

Mesenchymal Stem Cells Can Be Mobilized Into Peripheral Blood by Short-Term Hypoxia: a Possible Role of HIF-1α.

AbstractAbstract 1450 Background:Mesenchymal stem cells (MSCs) constitute a population of multipotential cells giving rise to adipocytes, osteoblasts and chondrocytes. Combining with their engraftment promoting capacity and immunosuppressive property, MSCs may be therapeutically useful for haematopoietic stem cell transplantation. There is growing evidence that these cells can, under the right circumstances, enter peripheral circulation. Previous study revealed that MSCs are mobilized into peripheral blood (PB) by 3 weeks of chronic hypoxia, but the mobilization effect of short-term hypoxia and the underlying mechanisms are currently unknown. In this study, we used rat model to determine whether short-term hypoxia can mobilize MSCs into PB and investigated the related factors which may regulate the mobilization process. Design and Methods:Rats were housed in a hypoxic chamber (FiO2=10%) for 1, 2, 3, 5, 7 and 14 days, respectively, while control ones were housed in normoxic environment for equal periods. To quantify the number of MSCs and evaluate mobilization efficiency, PB and bone barrow (BM) samples of each group were collected and colony-forming unit fibroblast (CFU-F) assays were performed. Mobilized PB derived MSCs were identified by immunophenotype and trilineage differentiation. Since BM is the main reservoir and typical microenvironment of MSCs, we investigated the response of BM environment exposed to hypoxia which may potentially facilitate MSCs mobilization. Hypoxia-inducible factor 1α (HIF-1α) expression of BM cells was detected by Western blot; vascular endothelial growth factor (VEGF) in BM was qualified by ELISA and Immunohistochemistry (IHC). To evaluate the change of BM sinusoid vessels (BMSVs), VEGFR3 was stained by IHC and positive vessels were counted. The levels of stromal cell-derived factor-1α (SDF-1α) and VEGF in PB were tested by ELISA. Moreover, we compared migration capacity of MSCs in hypoxic condition (PO2=1% or 8%) with normal condition (PO2=21%) in vitro using Transwell assay. Results:We found that MSCs were mobilized into PB by exposing to short-term hypoxia (2d) and the CFU-F frequency was 5.80±0.58 vs. 1.40±0.24 CFU-Fs per 3×106 cells (p<0.05, n=5). From 2d to 14d of hypoxic exposure, the number of CFU-Fs mobilized in PB of hypoxic group was gradually increased in a time dependent manner. However, no significant differences were observed in bone marrow CFU-Fs among varies groups (P>0.05). Mobilized PB derived adherent cells were positive for CD90, CD29 and CD44, but negative for CD34 and CD45 and they could differentiate into adipocyte, osteoblast, and chondrocyte, which indicated that mobilized PB-derived cells are bona fide MSCs. What's more, we showed here that during hypoxic exposure, HIF-1α was stabilized and expressed continuously in BM of rats which is a main niche of MSCs. Stabilization and up-regulation of HIF-1α suggested that BM is hypoxia-sensitive and during hypoxic exposure it became a lower oxygen environment (PO2<1%). Previous studies have proved that VEGF and SDF-1α are directly regulated by the transcription factor HIF-1α. Our results showed that, induced by HIF-1α, VEGF was elevated from 2d to 7d in the BM of hypoxic rats which may increase BM vascular permeability and induce vasodilatation; VEGFR3(+) BMSVs increased in 7d and 14d hypoxic BM which may further facilitate the egress of MSCs. SDF-1α in PB increased from 2d to 14d, especially 7d of hypoxia (1976.7±148.1 vs. 663.6±56.7pg/ml, P<0.01). In addition, exposure of MSCs to low oxygen (8% PO2) significantly promoted their in vitro migration and a further increase was observed under lower oxygen condition (1% PO2). MSCs migrated more rapidly in response to SDF-1α exposed to hypoxia. Conclusion:Taken together, we show here that MSCs can be mobilized into PB by short-term hypoxia and the mobilization efficacy increased in a time dependent manner. Our results suggest the mechanisms of hypoxia inducing MSCs mobilization relate to the lower oxygen milieu of BM and stabilization of HIF-1α may play a pivotal role in MSCs mobilization. Our data provide meaningful clues to clarify the mechanisms of MSCs mobilization and important evidence for further exploring the exact agents that of clinical use. Disclosures:No relevant conflicts of interest to declare.

Correlation of serum vascular endothelial growth factor levels with plasma,serum and P-APR in breast cancer

Objective To look for a better way to assay vascular endothelial growth factor(VEGF) and explore the correlation of serum VEGF levels with platelet and leucocyte count in breast cancer by comparison of peripheral blood plasma, serum and P-APR. Methods Blood samples were obtained from 42 patients with breast cancer and 20 healthy volunteers. Serum, plasma and P-APR samples were analyzed for VEGF using a commercially available sandwich ELISA, and assayed for semiquantitative measurement using microplatereader. At the same time, samples were analyzed by hematology analyzer. Results The level of VEGF in peripheral blood positively correlated to platelet (health control group: r=0.424, P=0.063) and leucocyte (health control group: r=0.443, P=0.050). The difference in VEGF values of P-APR between the localized breast cancer group and the health control group was statistically significant. Conclusion The level of VEGF in peripheral blood positively correlates to platelet and leucocyte. Platelet and leucocyte possibly secrete VEGF in vitro. Compared with serum and plasma, P-APR is the best section assaying VEGF in peripheral blood. Key words: Breast neoplasms; Vascular endothelial growth factor; , Blood platelets; Leukocytes