The purpose of the current study was to evaluate the effect of a high-fat (HF) diet, energy restriction and exercise on the expression of vascular endothelial growth factor (VEGF), angiopoietin (Ang) I and 2, an...The purpose of the current study was to evaluate the effect of a high-fat (HF) diet, energy restriction and exercise on the expression of vascular endothelial growth factor (VEGF), angiopoietin (Ang) I and 2, and their receptors in rat corpus cavernosum (CC). Male Wistar rats were fed adlibitum with an H F diet for 8 or 16 weeks. After 8 weeks of the H F diet, a group of rats was subjected to energy restriction with or without exercise for 8 weeks. Control animals had free access to standard diet for the same period. After euthanasia, blood was collected and the penises removed for immunofluorescence assays (VEGF, VEGF receptor (VEGFR) I and 2, Angl, Ang2 and Tie2) and semiquantification of VEGF, VEGFR 1, VEGFR2, Angl, Ang2, Tie2, endothelial nitric oxide synthase (eNOS) and Aktlphospho-Akt by Western blotting. HF diet-fed rats exhibited lower high-density lipoprotein cholesterol (HDL-c) levels, higher systolic blood pressure and an increased atherogenic index. A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway was activated by the HF diet. Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression. These results emphasize the role of diet on vascular function regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2 systems occurs before serum lipid changes and obesity onset, antedating structural atherosclerotic features.展开更多
A potential pathological role of angiopoietins (Ang) in glomeruli following podocyte injury-induced progressive glomerulosclerosis was explored. Eighty male Wistar rats were randomly allocated into sham operation gr...A potential pathological role of angiopoietins (Ang) in glomeruli following podocyte injury-induced progressive glomerulosclerosis was explored. Eighty male Wistar rats were randomly allocated into sham operation group (Sham, n= 25), Uninephrectomy group (UPHT, n= 25) and Uninephrectomy+Daunorubicin group (DRB, n= 30). In DRB group, daunorubicin (5 mg/kg) was injected via tail vein on the 7th and 14th day after uninephrectomy. At week 1, 2, 4, 6 and 8 respectively following establishment of the animal model, 5 rats in Sham group and UPHT group, and 6 in DRB group were taken respectively for determining 24-h urinary protein excretion rate (24hUPER), blood urea nitrogen (BUN) and serum creatinine (Scr). The sections of kidneys were examined by an electric microscope, PAS staining, immunohistochemical staining and in situ hy-bridization histochemistry. The results showed that 24hUPER, BUN and Scr in DRB group were more than those in Sham group and UPHT group at the same time points, and there was a trend towards an increase on level of GSI in DRB group from week 2 to week 8. Electric microscopy revealed that podocyte injury presented in DRB group. The expression of Angl mRNA and protein in glomeruli of DRB group was decreased, while the expression of Ang2 protein in glomeruli of DRB group increased. Meanwhile, the expression of Angl mRNA had a negative correlation with the expression of Ang2 mRNA, and the expression of Angl protein had a positive correlation with the expression of Angl mRNA, and had a negative correlation with 24hUPER, BUN, Scr, glomerular sclerotic index (GSI), the expression of Ang2 protein and CoIV protein. The expression of Ang2 protein had a positive correlation with the expression of Ang2 mRNA, and had a positive correlation with 24hUPER, BUN, Scr, GSI, the expression of CoIV protein. It was concluded that podocyte injury might lead to an alteration in the expression of Angl and Ang2 within glomeruli. Ang2 may get rid of inhibition from Angl for downregulation of the Angl expression, which facilitate upregulation of the Ang2 expression in glomeruli to promote progressive glomerulosclerosis in the rats.展开更多
OBJECTIVE: To explore the effect of two dominating signaling pathways, VEGF/KDR and angiopoietins/Tie2, on the formation of new blood vessel in hepatocellular carcinoma (HCC) growth and metastasis. METHODS: RT-PCR and...OBJECTIVE: To explore the effect of two dominating signaling pathways, VEGF/KDR and angiopoietins/Tie2, on the formation of new blood vessel in hepatocellular carcinoma (HCC) growth and metastasis. METHODS: RT-PCR and Western blot were employed to evaluate the VEGF/KDR and angiopoietins/Tie2 expression in samples from 23 patients with HCC. Meanwhile, microvessel density (MVD) was determined as a marker of angiogenesis by counting CD34 positive cells with the method of immunohistochemistry. RESULTS: The two pathways were activated in all HCC samples. The expressions of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2) were significantly higher (P<0.05) in hepatocellular carcinoma tissues and the margin of the tumor than those in control groups, and so did CD34 positive cells. Although significant difference in the expression of kinase insert domain containing receptor (KDR) and Ang1/Tie2 was not observed in all groups, their distinct high levels were seen in hepatoma and its margin compared with normal and cirrhotic liver. VEGF and Ang2 expressions were seen up-regulated in HCC with vascular invasion and satellite lesion. CONCLUSIONS: The two signaling pathways, VEGF/KDR and angiopoietins/Tie2 are activated in the process of angiogenesis in HCC and modulate the formation of new blood vessels. The imparity of the two signaling pathways' activation is to benefit HCC metastasis. In the two pathways, VEGF and Ang2 may play an important role in the process of angiogenesis, and are necessary indicators for the prognosis and metastasis of HCC. This study provides another clue for the exploration of anti-angiogenic agents.展开更多
Consuming a high-fructose diet induces metabolic syndrome (MS)-Iike features, including endothelial dysfunction. Erectile dysfunction is an early manifestation of endothelial dysfunction and systemic vascular diseas...Consuming a high-fructose diet induces metabolic syndrome (MS)-Iike features, including endothelial dysfunction. Erectile dysfunction is an early manifestation of endothelial dysfunction and systemic vascular disease. Because mineral deficiency intensifies the deleterious effects of fructose consumption and mineral ingestion is protective against MS, we aimed to characterize the effects of 8weeks of natural mineral-rich water consumption on the structural organization and expression of vascular growth factors and receptors on the corpus cavernosum (CC) in 10% fructose-fed Sprague-Dawley rats (FRUCT). Differences were not observed in the organization of the CC either on the expression of vascular endothelial growth factor (VEGF) or the components of the angiopoietins/Tie2 system. However, opposing expression patterns were observed for VEGF receptors (an increase and a decrease for VEGFR1 and VEGFR2, respectively) in FRUCT animals, with these patterns being strengthened by mineral-rich water ingestion. Mineral-rich water ingestion (FRUCTMIN) increased the proportion of smooth muscle cells compared with FRUCT rats and induced an upregulatory tendency of sirtuin I expression compared with the control and FRUCT groups. Western blot results were consistent with the dual immunofluorescence evaluation. Plasma oxidized low-density lipoprotein and plasma testosterone levels were similar among the experimental groups, although a tendency for an increase in the former was observed in the FRUCTMIN group. The mineral-rich water-treated rats presented changes similar to those observed in rats treated with MS-protective polyphenol-rich beverages or subjected to energy restriction, which led us to hypothesize that the effects of mineral-rich water consumption may be more vast than those directly observed in this study.展开更多
BACKGROUND Neovascularisation is common to a variety of gastrointestinal(GI)disorders with differing aetiologies and presentations;usually affecting adults above 60 years.Shared angiogenic factors modulated by disease...BACKGROUND Neovascularisation is common to a variety of gastrointestinal(GI)disorders with differing aetiologies and presentations;usually affecting adults above 60 years.Shared angiogenic factors modulated by disease specific elements could be a common denominator and represent novel diagnostic and therapeutic targets.As yet,assessment of angiogenic factors across several GI vascular disorders associated with recurrent bleeding and anaemia has not been reported.AIM To assess serum levels of angiogenic factors in several intestinal vascular disorders.METHODS A case control study was performed in Tallaght University Hospital in patients with endoscopically proven small bowel angiodysplasia(SBA),portal hypertensive gastropathy(PHG),gastric antral vascular ectasia(GAVE)and nonbleeding,non-anaemic controls.Using enzyme-linked immunosorbent assay,concentrations of Angiopoietin 1(Ang-1),Ang-2 and vascular endothelial growth factor(VEGF)were measured from 2 serum tubes of blood following informed consent.The relative expression of Ang-1 and Ang-2 and Ang-1/2 ratio was calculated and compared between groups.Statistical analysis was applied using a t-test,and a P value of<0.05 was considered significant.RESULTS To date 44 samples were tested:10 SBA,11 PHG,8 GAVE and 15 controls.Mean age 60(range 20-85)years and 20(45%)were males.Controls were significantly younger(49 years vs 66 years,P=0.0005).There was no difference in VEGF levels between the groups(P=0.6).SBA,PHG and GAVE Ang-1 levels were similar and were significantly lower than controls,(P=0.0002,95%CI:241 to 701).Ang-2 levels were statistically higher in PHG and GAVE groups compared to controls(P= 0.01, 95%CI: 77.8 to 668) and as a result, also had a lower Ang-1/2 ratioscompared to controls. While SBA Ang-2 levels were higher than controls, this didnot reach statistical significance. Neither age nor haemoglobin level, which wassimilar between disease groups, could explain the difference. In addition, themedian Ang-1/Ang-2 ratio for all patients was found to be significantly lowercompared to controls, 8 vs 28 respectively, P = 0.001, 95%CI: -27.55 to -7.12.CONCLUSIONOur novel pilot study suggests common alterations in Ang-1 and Ang-2 levelsacross several GI vascular disorders. Differences in Ang-1/Ang-2 ratios amongvascular disorders compared to controls suggest disease-specific modulation.展开更多
Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma(HCC) since 2007 and numerous studieshave investigated the role of markers involved in the angiogenesi...Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma(HCC) since 2007 and numerous studieshave investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC.展开更多
·AIM: To determine the effects of laser photocoagulation on serum levels of angiopoietin-1(Ang-1),angiopoietin-2(Ang-2), soluble angiopoietin receptor Tie-2(Tie-2), Ang-1/Ang-2 ratio and vascular endothelial grow...·AIM: To determine the effects of laser photocoagulation on serum levels of angiopoietin-1(Ang-1),angiopoietin-2(Ang-2), soluble angiopoietin receptor Tie-2(Tie-2), Ang-1/Ang-2 ratio and vascular endothelial growth factor(VEGF) in patients with type 2diabetes mellitus(T2DM) and proliferative diabetic retinopathy(PDR). We also explored the role of the Ang/Tie system in PDR.·METHODS:Totally 160patientswithT2 DM, including50 patients with non-diabetic retinopathy(NDR), 58 patients with non-proliferative diabetic retinopathy(NPDR), and52 patients with PDR were enrolled in this study. Serum Ang-1, Ang-2, Tie-2 receptor and VEGF levels were measured using enzyme-linked immunosorbent assays for all patients and were repeated in 26 patients who underwent laser photocoagulation two months after the procedure.·RESULTS:ThemedianlevelsofAng-2andVEGFinserum were significantly higher in the NPDR group(4.23 ng/mL and 303.2 pg/mL, respectively) compared to the NDR group(2.67 ng/mL and 159.8 pg/mL, respectively, P 【0.01), with the highest level in the PDR group(6.26 ng/mL and531.2 pg/mL, respectively, P 【0.01). The median level of Ang-1 was significantly higher in the NPDR group(10.77ng/mL) compared to the NDR group(9.31 ng/mL) and the PDR groups(9.54 ng/mL)(P 【0.05), while no difference was observed between the PDR and NDR groups. Ang-1/Ang-2 ratio of PDR group was lowest in three groups(1.49 vs 2.69 and 2.90, both P 【0.01). The median level of Tie-2was not significantly different among three groups(P 】0.05).Ang-2 was positively correlated with VEGF and Tie-2 in the PDR and NPDR groups(both P 【0.05). Among the 26 patients who underwent laser photocoagulation, serum Ang-2 and VEGF levels significantly decreased(both P 【0.05), whereas serum Ang-1 level and Ang-1/Ang-2ratio were weakly increased(P 】0.05). The median levels of Ang-2 and VEGF in serum were highest in PDR group,however, Ang-1/Ang-2 ratio of PDR group was lowest in three groups.·CONCLUSION: Laser photocoagulation can reduce serum Ang-2 and VEGF levels. The Ang/Tie system and VEGF play an important role in the development and progression of T2 DM patients with PDR.展开更多
AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this dru...AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2(Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound VEGF levels were measured at baseline, before 2^(nd) and 5^(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2^(nd) and the 5^(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.展开更多
AIM To explore expression of angiopoietin-like protein 2(ANGpT L2) and its effect on biological behavior such as proliferation and invasiveness in gastric cancer. METHODS Western blotting was used to detect expression...AIM To explore expression of angiopoietin-like protein 2(ANGpT L2) and its effect on biological behavior such as proliferation and invasiveness in gastric cancer. METHODS Western blotting was used to detect expression of ANGp TL2 in 60 human normal gastric tissues, 60 human gastric cancer tissues and gastric cell lines including GES-1, N87, SGC7901, BGC823 and pA MC82. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) and Transwell assay were used to detect the proliferation and invasive ability of gastric cancer cells. RESULTS Compared to normal tissues, ANGp TL2 protein levels were significantly upregulated in gastric tissues, and this level was closely correlated with gastric tumor grade, clinical stage and lymph node metastasis. Compared to GES-1 cells, ANGpT L2 mR NA and protein levels were significantly increased in gastric cancer cells including N87, SGC7901, BGC823 and p AMC82. The expression of ANGpT L2 in highly malignant gastric cancer cell lines BGC823 and pA MC82 was significantly higher than in low malignancy gastric cancer cell lines N87 and SGC7901. MTT and Transwell experiments indicated that the proliferation rate and invasive ability of stable overexpressed gastric cancer cells was faster than in cells transfected with Lv-NC and blank controlcells, and the invasive ability of stable overexpressed gastric cancer cells was higher than that of cells transfected with Lv-NC and blank control cells.CONCLUSION ANGp TL2 contributed to proliferation and invasion of gastric cancer cells. In clinical treatment, ANGpT L2 may become a new target for treatment of gastric cancer.展开更多
Objective:To investigate the effect of Moringa oleifera leaf extract on angiogenesis and inflammatory process in a rat model of streptozotocin-induced diabetic nephropathy.Methods:Four weeks after a single injection o...Objective:To investigate the effect of Moringa oleifera leaf extract on angiogenesis and inflammatory process in a rat model of streptozotocin-induced diabetic nephropathy.Methods:Four weeks after a single injection of 50 mg/kg streptozotocin,rats were treated with 100 or 200 mg/kg/day Moringa oleifera leaf extract,1 mg/kg/day dapagliflozin,or a combination of Moringa oleifera leaf extract and dapagliflozin for further eight weeks.Renal function,kidney histology,and gene expression were evaluated at the end of the experiment.Results:Renal function of diabetic rats was significantly impaired as evidenced by increased blood urea nitrogen,albuminuria,24-h proteinuria,and high creatinine clearance which indicated glomerular hyperfiltration.In addition,diabetic rats showed an increase in gene expressions of vascular endothelial growth factor-A(VEGF-A),angiopoietin-2(Ang2),the Ang2/Ang1 ratio,tumor necrosis factor-α,interleukin-1βand monocyte chemoattractant protein-1.Immunohistochemical staining demonstrated a significant increase in the density of glycoprotein CD34.Moringa oleifera leaf extract markedly improved all renal dysfunction markers and modulated the upregulated expression of angiogenic factors and inflammatory genes.Conclusions:Moringa oleifera leaf extract could suppress abnormal angiogenesis and inflammatory processes possibly by downregulating gene expression of angiogenesis factors and proinflammatory cytokines.展开更多
文摘The purpose of the current study was to evaluate the effect of a high-fat (HF) diet, energy restriction and exercise on the expression of vascular endothelial growth factor (VEGF), angiopoietin (Ang) I and 2, and their receptors in rat corpus cavernosum (CC). Male Wistar rats were fed adlibitum with an H F diet for 8 or 16 weeks. After 8 weeks of the H F diet, a group of rats was subjected to energy restriction with or without exercise for 8 weeks. Control animals had free access to standard diet for the same period. After euthanasia, blood was collected and the penises removed for immunofluorescence assays (VEGF, VEGF receptor (VEGFR) I and 2, Angl, Ang2 and Tie2) and semiquantification of VEGF, VEGFR 1, VEGFR2, Angl, Ang2, Tie2, endothelial nitric oxide synthase (eNOS) and Aktlphospho-Akt by Western blotting. HF diet-fed rats exhibited lower high-density lipoprotein cholesterol (HDL-c) levels, higher systolic blood pressure and an increased atherogenic index. A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway was activated by the HF diet. Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression. These results emphasize the role of diet on vascular function regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2 systems occurs before serum lipid changes and obesity onset, antedating structural atherosclerotic features.
文摘A potential pathological role of angiopoietins (Ang) in glomeruli following podocyte injury-induced progressive glomerulosclerosis was explored. Eighty male Wistar rats were randomly allocated into sham operation group (Sham, n= 25), Uninephrectomy group (UPHT, n= 25) and Uninephrectomy+Daunorubicin group (DRB, n= 30). In DRB group, daunorubicin (5 mg/kg) was injected via tail vein on the 7th and 14th day after uninephrectomy. At week 1, 2, 4, 6 and 8 respectively following establishment of the animal model, 5 rats in Sham group and UPHT group, and 6 in DRB group were taken respectively for determining 24-h urinary protein excretion rate (24hUPER), blood urea nitrogen (BUN) and serum creatinine (Scr). The sections of kidneys were examined by an electric microscope, PAS staining, immunohistochemical staining and in situ hy-bridization histochemistry. The results showed that 24hUPER, BUN and Scr in DRB group were more than those in Sham group and UPHT group at the same time points, and there was a trend towards an increase on level of GSI in DRB group from week 2 to week 8. Electric microscopy revealed that podocyte injury presented in DRB group. The expression of Angl mRNA and protein in glomeruli of DRB group was decreased, while the expression of Ang2 protein in glomeruli of DRB group increased. Meanwhile, the expression of Angl mRNA had a negative correlation with the expression of Ang2 mRNA, and the expression of Angl protein had a positive correlation with the expression of Angl mRNA, and had a negative correlation with 24hUPER, BUN, Scr, glomerular sclerotic index (GSI), the expression of Ang2 protein and CoIV protein. The expression of Ang2 protein had a positive correlation with the expression of Ang2 mRNA, and had a positive correlation with 24hUPER, BUN, Scr, GSI, the expression of CoIV protein. It was concluded that podocyte injury might lead to an alteration in the expression of Angl and Ang2 within glomeruli. Ang2 may get rid of inhibition from Angl for downregulation of the Angl expression, which facilitate upregulation of the Ang2 expression in glomeruli to promote progressive glomerulosclerosis in the rats.
文摘OBJECTIVE: To explore the effect of two dominating signaling pathways, VEGF/KDR and angiopoietins/Tie2, on the formation of new blood vessel in hepatocellular carcinoma (HCC) growth and metastasis. METHODS: RT-PCR and Western blot were employed to evaluate the VEGF/KDR and angiopoietins/Tie2 expression in samples from 23 patients with HCC. Meanwhile, microvessel density (MVD) was determined as a marker of angiogenesis by counting CD34 positive cells with the method of immunohistochemistry. RESULTS: The two pathways were activated in all HCC samples. The expressions of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2) were significantly higher (P<0.05) in hepatocellular carcinoma tissues and the margin of the tumor than those in control groups, and so did CD34 positive cells. Although significant difference in the expression of kinase insert domain containing receptor (KDR) and Ang1/Tie2 was not observed in all groups, their distinct high levels were seen in hepatoma and its margin compared with normal and cirrhotic liver. VEGF and Ang2 expressions were seen up-regulated in HCC with vascular invasion and satellite lesion. CONCLUSIONS: The two signaling pathways, VEGF/KDR and angiopoietins/Tie2 are activated in the process of angiogenesis in HCC and modulate the formation of new blood vessels. The imparity of the two signaling pathways' activation is to benefit HCC metastasis. In the two pathways, VEGF and Ang2 may play an important role in the process of angiogenesis, and are necessary indicators for the prognosis and metastasis of HCC. This study provides another clue for the exploration of anti-angiogenic agents.
文摘Consuming a high-fructose diet induces metabolic syndrome (MS)-Iike features, including endothelial dysfunction. Erectile dysfunction is an early manifestation of endothelial dysfunction and systemic vascular disease. Because mineral deficiency intensifies the deleterious effects of fructose consumption and mineral ingestion is protective against MS, we aimed to characterize the effects of 8weeks of natural mineral-rich water consumption on the structural organization and expression of vascular growth factors and receptors on the corpus cavernosum (CC) in 10% fructose-fed Sprague-Dawley rats (FRUCT). Differences were not observed in the organization of the CC either on the expression of vascular endothelial growth factor (VEGF) or the components of the angiopoietins/Tie2 system. However, opposing expression patterns were observed for VEGF receptors (an increase and a decrease for VEGFR1 and VEGFR2, respectively) in FRUCT animals, with these patterns being strengthened by mineral-rich water ingestion. Mineral-rich water ingestion (FRUCTMIN) increased the proportion of smooth muscle cells compared with FRUCT rats and induced an upregulatory tendency of sirtuin I expression compared with the control and FRUCT groups. Western blot results were consistent with the dual immunofluorescence evaluation. Plasma oxidized low-density lipoprotein and plasma testosterone levels were similar among the experimental groups, although a tendency for an increase in the former was observed in the FRUCTMIN group. The mineral-rich water-treated rats presented changes similar to those observed in rats treated with MS-protective polyphenol-rich beverages or subjected to energy restriction, which led us to hypothesize that the effects of mineral-rich water consumption may be more vast than those directly observed in this study.
基金We thank all the volunteers and medical staff who agreed to participate in this study.
文摘BACKGROUND Neovascularisation is common to a variety of gastrointestinal(GI)disorders with differing aetiologies and presentations;usually affecting adults above 60 years.Shared angiogenic factors modulated by disease specific elements could be a common denominator and represent novel diagnostic and therapeutic targets.As yet,assessment of angiogenic factors across several GI vascular disorders associated with recurrent bleeding and anaemia has not been reported.AIM To assess serum levels of angiogenic factors in several intestinal vascular disorders.METHODS A case control study was performed in Tallaght University Hospital in patients with endoscopically proven small bowel angiodysplasia(SBA),portal hypertensive gastropathy(PHG),gastric antral vascular ectasia(GAVE)and nonbleeding,non-anaemic controls.Using enzyme-linked immunosorbent assay,concentrations of Angiopoietin 1(Ang-1),Ang-2 and vascular endothelial growth factor(VEGF)were measured from 2 serum tubes of blood following informed consent.The relative expression of Ang-1 and Ang-2 and Ang-1/2 ratio was calculated and compared between groups.Statistical analysis was applied using a t-test,and a P value of<0.05 was considered significant.RESULTS To date 44 samples were tested:10 SBA,11 PHG,8 GAVE and 15 controls.Mean age 60(range 20-85)years and 20(45%)were males.Controls were significantly younger(49 years vs 66 years,P=0.0005).There was no difference in VEGF levels between the groups(P=0.6).SBA,PHG and GAVE Ang-1 levels were similar and were significantly lower than controls,(P=0.0002,95%CI:241 to 701).Ang-2 levels were statistically higher in PHG and GAVE groups compared to controls(P= 0.01, 95%CI: 77.8 to 668) and as a result, also had a lower Ang-1/2 ratioscompared to controls. While SBA Ang-2 levels were higher than controls, this didnot reach statistical significance. Neither age nor haemoglobin level, which wassimilar between disease groups, could explain the difference. In addition, themedian Ang-1/Ang-2 ratio for all patients was found to be significantly lowercompared to controls, 8 vs 28 respectively, P = 0.001, 95%CI: -27.55 to -7.12.CONCLUSIONOur novel pilot study suggests common alterations in Ang-1 and Ang-2 levelsacross several GI vascular disorders. Differences in Ang-1/Ang-2 ratios amongvascular disorders compared to controls suggest disease-specific modulation.
文摘Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma(HCC) since 2007 and numerous studieshave investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC.
文摘·AIM: To determine the effects of laser photocoagulation on serum levels of angiopoietin-1(Ang-1),angiopoietin-2(Ang-2), soluble angiopoietin receptor Tie-2(Tie-2), Ang-1/Ang-2 ratio and vascular endothelial growth factor(VEGF) in patients with type 2diabetes mellitus(T2DM) and proliferative diabetic retinopathy(PDR). We also explored the role of the Ang/Tie system in PDR.·METHODS:Totally 160patientswithT2 DM, including50 patients with non-diabetic retinopathy(NDR), 58 patients with non-proliferative diabetic retinopathy(NPDR), and52 patients with PDR were enrolled in this study. Serum Ang-1, Ang-2, Tie-2 receptor and VEGF levels were measured using enzyme-linked immunosorbent assays for all patients and were repeated in 26 patients who underwent laser photocoagulation two months after the procedure.·RESULTS:ThemedianlevelsofAng-2andVEGFinserum were significantly higher in the NPDR group(4.23 ng/mL and 303.2 pg/mL, respectively) compared to the NDR group(2.67 ng/mL and 159.8 pg/mL, respectively, P 【0.01), with the highest level in the PDR group(6.26 ng/mL and531.2 pg/mL, respectively, P 【0.01). The median level of Ang-1 was significantly higher in the NPDR group(10.77ng/mL) compared to the NDR group(9.31 ng/mL) and the PDR groups(9.54 ng/mL)(P 【0.05), while no difference was observed between the PDR and NDR groups. Ang-1/Ang-2 ratio of PDR group was lowest in three groups(1.49 vs 2.69 and 2.90, both P 【0.01). The median level of Tie-2was not significantly different among three groups(P 】0.05).Ang-2 was positively correlated with VEGF and Tie-2 in the PDR and NPDR groups(both P 【0.05). Among the 26 patients who underwent laser photocoagulation, serum Ang-2 and VEGF levels significantly decreased(both P 【0.05), whereas serum Ang-1 level and Ang-1/Ang-2ratio were weakly increased(P 】0.05). The median levels of Ang-2 and VEGF in serum were highest in PDR group,however, Ang-1/Ang-2 ratio of PDR group was lowest in three groups.·CONCLUSION: Laser photocoagulation can reduce serum Ang-2 and VEGF levels. The Ang/Tie system and VEGF play an important role in the development and progression of T2 DM patients with PDR.
文摘AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2(Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound VEGF levels were measured at baseline, before 2^(nd) and 5^(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2^(nd) and the 5^(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.
文摘AIM To explore expression of angiopoietin-like protein 2(ANGpT L2) and its effect on biological behavior such as proliferation and invasiveness in gastric cancer. METHODS Western blotting was used to detect expression of ANGp TL2 in 60 human normal gastric tissues, 60 human gastric cancer tissues and gastric cell lines including GES-1, N87, SGC7901, BGC823 and pA MC82. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) and Transwell assay were used to detect the proliferation and invasive ability of gastric cancer cells. RESULTS Compared to normal tissues, ANGp TL2 protein levels were significantly upregulated in gastric tissues, and this level was closely correlated with gastric tumor grade, clinical stage and lymph node metastasis. Compared to GES-1 cells, ANGpT L2 mR NA and protein levels were significantly increased in gastric cancer cells including N87, SGC7901, BGC823 and p AMC82. The expression of ANGpT L2 in highly malignant gastric cancer cell lines BGC823 and pA MC82 was significantly higher than in low malignancy gastric cancer cell lines N87 and SGC7901. MTT and Transwell experiments indicated that the proliferation rate and invasive ability of stable overexpressed gastric cancer cells was faster than in cells transfected with Lv-NC and blank controlcells, and the invasive ability of stable overexpressed gastric cancer cells was higher than that of cells transfected with Lv-NC and blank control cells.CONCLUSION ANGp TL2 contributed to proliferation and invasion of gastric cancer cells. In clinical treatment, ANGpT L2 may become a new target for treatment of gastric cancer.
基金supported by the Cardiovascular Research Group,Khon Kaen University and the Faculty of Medicine,Khon Kaen University,Thailand(grant number IN63355).
文摘Objective:To investigate the effect of Moringa oleifera leaf extract on angiogenesis and inflammatory process in a rat model of streptozotocin-induced diabetic nephropathy.Methods:Four weeks after a single injection of 50 mg/kg streptozotocin,rats were treated with 100 or 200 mg/kg/day Moringa oleifera leaf extract,1 mg/kg/day dapagliflozin,or a combination of Moringa oleifera leaf extract and dapagliflozin for further eight weeks.Renal function,kidney histology,and gene expression were evaluated at the end of the experiment.Results:Renal function of diabetic rats was significantly impaired as evidenced by increased blood urea nitrogen,albuminuria,24-h proteinuria,and high creatinine clearance which indicated glomerular hyperfiltration.In addition,diabetic rats showed an increase in gene expressions of vascular endothelial growth factor-A(VEGF-A),angiopoietin-2(Ang2),the Ang2/Ang1 ratio,tumor necrosis factor-α,interleukin-1βand monocyte chemoattractant protein-1.Immunohistochemical staining demonstrated a significant increase in the density of glycoprotein CD34.Moringa oleifera leaf extract markedly improved all renal dysfunction markers and modulated the upregulated expression of angiogenic factors and inflammatory genes.Conclusions:Moringa oleifera leaf extract could suppress abnormal angiogenesis and inflammatory processes possibly by downregulating gene expression of angiogenesis factors and proinflammatory cytokines.