Angiogenesis factor of human osteosarcoma was partially purified and its biological features were studied. The active peptide with 8000 to 10 000 u molecular weight in the conditioned medium obtained from the cultiva...Angiogenesis factor of human osteosarcoma was partially purified and its biological features were studied. The active peptide with 8000 to 10 000 u molecular weight in the conditioned medium obtained from the cultivation of human osteosarcoma cells were partially purified by ultrafiltration, chromatography and dialysis. The angiogenic effects of the fractions were assessed by proliferation assay of human umbilical vein and pig aorta thoracic endothelial cells. The results showed that the chromatography fractions of 4 to 6 could significantly promote the proliferation of the endothelial cells. It was suggested that the human osteosarcoma cells could synthesize and secrete angiogenesis factor with a molecular weight of 8000 to 10 000 u.展开更多
Background Hypoxia-inducible factor (HIF) may play an important role in the process of tumorigenesis as well as tumor progression. The aim of this study was to compare the expression between HIF-1α and HIF-2α in t...Background Hypoxia-inducible factor (HIF) may play an important role in the process of tumorigenesis as well as tumor progression. The aim of this study was to compare the expression between HIF-1α and HIF-2α in tumor angiogenesis and the overall impact on patient prognosis in human non-small cell lung cancer (NSCLC). Methods In the current work we compared the immunohistochemical expression of HIF-1α and HIF-21 in surgical specimens of 140 patients with NSCLC in a tissue microarray study. Relationships between HIF-α expression and clinicopathological or angiogenic factors, including prognosis, were analyzed. Results High HIF-1α and HIF-2α expression was noted in 49/140 (35.0%) and in 64/140 (45.7%) of the cases, respectively. There was no direct correlation between HIF-la and HIF-2α expression. Patients with advanced stage tumors had frequent high expression of HIF-2a (P=0.007), and we also found a significant correlation between HIF-2α and T or N stage (P=0.030 and 0.043, respectively). HIF-1α showed a marginal association with T stage (P=0.084), which showed a higher expression in early stage tumors. A significant correlation (p=0.045) was noticed between HIF-1α and vascular endothelial growth factor (VEGF) expression while the expression levels of thymidine phosphorylase (TP), cyclooxygenase (COX)-2 and microvessel density (MVD) were significantly higher in high HIF-2a tumors (P=0.020, 0.004 and 0.046, respectively). In addition, univariate analysis of overall survival demonstrated that HIF-2a expression, but not HIF-la, was related to poor outcome (P=-0.001) and it retained significant in multivariate analysis (P=0.036). Conclusions Taken together, we conclude that HIF-1α and HIF-2α may differentially regulate the major angiogenic factors in different stages of the tumor process in NSCLC. HIF-2α may play a dominant role in tumor angiogenesis and appears to be of obvious value as a significant prognostic factor in NSCLC.展开更多
We previously showed that the repair of bone defects is regulated by neural and vascular signals. In the present study, we examined the effect of topically applied β-nerve growth factor(β-NGF) on neurogenesis and ...We previously showed that the repair of bone defects is regulated by neural and vascular signals. In the present study, we examined the effect of topically applied β-nerve growth factor(β-NGF) on neurogenesis and angiogenesis in critical-sized bone defects filled with collagen bone substitute. We created two symmetrical defects, 2.5 mm in diameter, on either side of the parietal bone of the skull, and filled them with bone substitute. Subcutaneously implanted osmotic pumps were used to infuse 10 μgβ-NGF in PBS(β-NGF + PBS) into the right-hand side defect, and PBS into the left(control) defect, over the 7 days following surgery. Immunohistochemical staining and hematoxylin-eosin staining were carried out at 3, 7, 14, 21 and 28 days postoperatively. On day 7, expression of β III-tubulin was lower on the β-NGF + PBS side than on the control side, and that of neurofilament 160 was greater. On day 14, β III-tubulin and protein gene product 9.5 were greater on the β-NGF + PBS side than on the control side. Vascular endothelial growth factor expression was greater on the experimental side than the control side at 7 days, and vascular endothelial growth factor receptor 2 expression was elevated on days 14 and 21, but lower than control levels on day 28. However, no difference in the number of blood vessels was observed between sides. Our results indicate that topical application of β-NGF promoted neurogenesis, and may modulate angiogenesis by promoting nerve regeneration in collagen bone substitute-filled defects.展开更多
BACKGROUND: Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor (VEGF) on in...BACKGROUND: Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor (VEGF) on inducing angiogenesis following ischemia/reperfusion injury can provide better help for the long-term treatment of cerebrovascular disease in clinic. OBJECTIVE: To observe the effect of VEGF on inducing angiogenesis following focal cerebral ischemia /reperfusion injury in rabbits through the angiogenesis of microvessels reflected by the expression of the factors of vascular pseudohemophilia. DESIGN: A randomized controlled animal tria SETTNG: Department of Medical Imaging, Second Hospital of Hebei Medical University MATERIALS: Sixty-five healthy male New Zealand rabbits of clean degree, weighing (2.6±0.2) kg, aged 4.5-5 months, were used. The polyclonal antibody against vascular pseudohemophilia (Beijing Zhongshan Company), recombinant VEGF165 (Peprotech Company, USA), biotinylated second antibody and ABC compound (Wuhan Boster Company) were applied. METHODS: The experiments were carried out in the Laboratory of Neuromolecular Imaging and Neuropathy, Second Hospital of Hebei Medical University from May to August in 2005. (1) The rabbits were randomly divided into three groups: sham-operated group (n=15), control group (n=25) and VEGF-treated group (n=-25). In the control group and VEGF-treated group, models were established by middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia/reperfusion. In the VEGF-treated group, VEGF165 (2.5 mg/L) was stereotactically injected into the surrounding regions of the infarcted sites immediately after the 2-hour ischemia/reperfusion; Saline of the same dosage was injected in the control group. But the rabbits in the sham-operated group were only drilled but not administrated. (2) The experimental indexes were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment respectively, 3 rabbits in the sham-operated group and 5 in the control group and VEGF-treated group were observed at each time point. The brain tissues in the surrounding regions of the infarcted sites were collected. The positive expressions of the factors of vascular pseudohemophilia in vascular endothelial cells were analyzed with immunohistochemical method. The microvessels in unit statistical field were counted with the imaging analytical software. MAIN OUTCOME MEASURES: The changes of microvascular density in the brain tissue and the positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of the infarcted sites were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment. RESULTS: All the 65 New Zealand rabbits were involved in the analysis of results without deletion. Changes of the number of microvessels at different time points in each group: There were no obvious changes at different time points in the sham-operated group. The numbers of microvessels at 7 and 14 days were obviously more in the control group than in the sham-operated group [(6.0±1.1), (9.0±0.9) microvessels; (3.0±1.1), (3.0±1.1) microvessels; P〈 0.05-0.01], and those at 3, 7, 14 and 28 days were obviously more in the VEGF-treated group than in the control group [(8.3±2.0), (13.4±1.4), (15.5±2.3), (6.8± 1.0) microvessels; (3.4±0.6), (6.0±1.1), (9.0±0.9), (3.2±0.8) microvessels; P 〈 0.01]. (2) Positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of infarcted sites: There were no obvious changes at different time points in the sham-operated group. In the control group, the changing law of the expressions was the same as that for the number of microvessels that the expression began to mildly increase at 7 days, reached the peak value at 14 days, and began to reduce at 28 days. In the VEGF-treated group, the expression was obviously increased at 3 days, also reached the peak value at 14 days, and reduced to the normal level at 70 days, but the expressions were obviously stronger than those in the control group at the same time points. CONCLUSION: Angiogenesis can be obviously induced in rabbits after the focal cerebral ischemia/reperfusion injury is treated with VEGF for 18 days.展开更多
Objective: To investigate the relation of vascular endothelial growth factor (VEGF) expression with angiogenesis and cell proliferation in malignant glioma in children. Methods: Immunohistochemical technique was used ...Objective: To investigate the relation of vascular endothelial growth factor (VEGF) expression with angiogenesis and cell proliferation in malignant glioma in children. Methods: Immunohistochemical technique was used to detect the expression of VEGF, microvessel quantity (MVQ) and PCNA Labeling Index (PCNA LI) in 33 malignant gliomas in children Results: Positive staining for VEGF was obtained in 23 out of the 33 cases (69.7). The MVQ and PCNA LI in VEFG-positive tumors were significantly higher than those in VEGF-negative tumors (P<0.005). The expression of VEGF in tumor tissues was significantly correlative with MVQ and PCNA LI (r=0.52 and 0.37, respectively, P<0.001). Conclusion: VEGF can be synthesized in tumor cells of malignant glioma in children which might play a significant role in angiogenesis and cell proliferation in the tumor.展开更多
BACKGROUND: In the process of vascularization, vascular endothelial growth factor (VEGF), angiopoietin-2 and Tie2 are involved in the migration, differentiation and proliferation of vascular endothelial cells, and ...BACKGROUND: In the process of vascularization, vascular endothelial growth factor (VEGF), angiopoietin-2 and Tie2 are involved in the migration, differentiation and proliferation of vascular endothelial cells, and stimulate the rapid angiogenesis; Tiel and angiopoietin-1 play important roles in facilitating the formation of vascular lumen and maintaining the integrity of vascular wall. Thus the distributions and expressions may be associated with the occurrence of cerebral arteriovenous malformation. OBJECTIVE: To observe the biological effects of angiogenic factors in the occurrence and development of cerebral arteriovenous malformation. DESIGN: An observational comparative experiment. SETTINGS: Department of Neurosurgery, General Hospital of Shenyang Military Area Command of Chinese PLA; Department of Neurosurgery, General Hospital of Tianjin Medical University. PARTICIPANTS: Fresh samples of complete cerebral arteriovenous malformations resected in 47 patients were collected from the Department of Neurosurgery, General Hospital of Tianjin Medical University from August 1999 to May 2001, including 22 males and 25 females, the mean age was 34.5 years. Informed consents were obtained from all the patients or their relatives. The initial symptom was hemorrhage in 28 cases. All the patients were classified according to the clinical imaging data and Spetzler-Martin grading standard, including 11 cases of grade Ⅰ, 17 cases of grade Ⅱ, 11 cases of grade Ⅲ, and 8 cases of grade Ⅳ - Ⅴ. Normal brain tissues resected by decompression due to trauma were taken from 8 patients as controls, including 5 males and 3 females, aging 12 - 65 years. METHODS: ① The expressions of VEGF, Tie receptors, angiopoietin-1, angiopoietin-2, proto-oncogene c-myc and proliferating cell nuclear antigen(PCNA) in the samples of cerebral arteriovenous malformation were detected with immunohistochemical method. Under light microscope, the positively stained rat-anti-human factor Ⅷ-related antigens (specific marker of vascular endothelial cells) were counted, then the immuno-positive cells of the other antibodies in the visual field of neighboring section which was in "mirror" relation were counted, and the percentage of the latter to the former was considered as the labeling index of positive cells. The immunostaining intensity was classified negative ( - ): no positive cells; positive (+): number of positive cells 〈 20%; moderately positive (++): number of positive cells 20% - 50%; strongly positive (+++): number of positive cells 〉 50%. ② The differences of the enumeration data were compared with chi-squam test, and the correlation were analyzed with the linear correlation analysis. MAIN OUTCOME MEASURES: Expressions and distributions of VEGF, Tie 1 and Tie2 receptors, angiopoietin-1, angiopoietin-2, PCNA and c-myc in the samples of cerebral arteriovenons malformation and normal brain tissue. RESULTS: ① Expressions of angiogenic factors in the control group and cerebral arteriovenons malformation groups of each grade: The positive rates of VEGF, Tie2, angiopoietin-2, c-myc and PCNA expressions in the control group were significantly different from those in the cerebral arteriovenous malformation groups of each grade ( x^2=21.09 - 34.23, P 〈 0.05), whereas the positive rates of Tiel and angiopoietin-1 expressions were close ( x^2=3.43 - 3.869, P 〉 0.05). ② Expressions of angiogenic factors in hemorrhage group and non-hemorrhage group: The expressions of VEGF, angiopoietin-2 and PCNA in the hemorrhage group were significantly lower than those in the non-hemorrhage group ( x^2= 16.22 - 26.56, P 〈 0.05). There ware no obvious differences in the expressions of Tiel and angiopoietin-1 expressions between the hemorrhage group and non-hemorrhage group ( x^2=3.22 - 3.78, P 〉 0.05).The VEGF was positively correlated with the expressions of c-myc and PCNA (r = 0.728, 0.916, P 〈 0.05). CONCLUSION: ①The expressions of angiogenic factors and related receptors may be involved in the process of cerebral arteriovenous malformation, and had important correlation the its clinical grading. ② Angiogenic factors may induce the expression of endothelial cell c-myc in cerebral arteriovenous malformation, and then interfere the cell proliferation and apoptosis.展开更多
Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury,but the underlying mechanisms remain unclear.In this study,rats were intragastrically given Buyanghuanwu decoction,15 m L/k...Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury,but the underlying mechanisms remain unclear.In this study,rats were intragastrically given Buyanghuanwu decoction,15 m L/kg,for 3 days.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.In rats administered Buyanghuanwu decoction,infarct volume was reduced,serum vascular endothelial growth factor and integrin αvβ3 levels were increased,and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals.These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor(administered through the lateral ventricle for 7 consecutive days).These data suggest that Buyanghuanwu decoction promotes angiogenesis,improves cerebral circulation,and enhances brain tissue repair after cerebral ischemia/reperfusion injury.展开更多
To study the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in esophageal squamous cell carcinoma (ESCC) and clarify the association of VEGF expression with the angiogenesis and ...To study the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in esophageal squamous cell carcinoma (ESCC) and clarify the association of VEGF expression with the angiogenesis and prognostic value of this disease. Methods: Eighty-two cases with primary ESCC treated with radical operation in Department of Surgery from Jan 1981 through May 1994 were enrolled. VEGF expression and MVD value were examined by immunohistochemical staining, the streptavidin-biotin peroxidase complex method (SP method), using anti-VEGF polyclonal antibody and anti-Factor-VIII antibody, respectively. We also analyzed the relationship between VEGF expression and MVD value and postoperative survival rate of patients. Results: Of the 82 cases, 63.4% cases showed positive for VEGF in tumor cells and the median of MVD in tumor was 37 (9-150)·mm-2. There was a close correlation between MVD and VEGF (P=0.001). The 5-year survival rate of patients with low and high MVD was 34.1% and 12.2%, respectively. The 5-year survival rate was 46.7% in patients with VEGF-negative tumor and 11.5% in patients with VEGF-positive tumor. These differences were statistically significant (P=0.017 and P<0.001, respectively). Conclusion: In ESCC, angiogenesis is mediated mainly by VEGF and VEGF may be associated with tumor progression and increased malignancy via angiogenesis.展开更多
This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to110 of gestation with either rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)on placental amino acid(...This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to110 of gestation with either rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)on placental amino acid(AA)transport,angiogenic gene expression,and steroid anabolism.On d 35 of gestation,32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups,each consisting of eight ewes,and were fed the following diets:A diet providing 100%of NRC’s nutrient requirements for pregnant ewes(CON);A diet providing 50%of NRC’s nutrient requirements for pregnant ewes(RES);RES diet plus 5 g/d NCG(RES+NCG);or RES diet plus 20 g/d RP-Arg(RES+ARG).On the d 110 of pregnancy,blood samples were taken from the mother,and samples were collected from type A cotyledons(COT;the fetal portions of the placenta).The levels of 17β-estradiol and progesterone in the maternal serum and both the capillary area density(CAD)and capillary surface density(CSD)in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group.The concentrations of arginine,leucine,putrescine and spermidine in type A COT were higher(P<0.05)in the RES+ARG or RES+NCG group than in the RES group.The mRNA expression levels of inducible nitric oxide synthase(iNOS)and solute carrier family 15,member 1(SLC15A1)were increased(P<0.05)while those of progesterone receptor(PGR)and fibroblast growth factor 2(FGF2)were decreased in type A COT by supplementation with either NCG or RP-Arg compared to the RES group.The results suggest that providing underfed pregnant ewes from d 35 to 110 of gestation with a diet supplemented with NCG or RP-Arg improves placental AA transport,and reduces the expression of angiogenic growth factor genes and steroid anabolism,leading to better fetal development.展开更多
The formation of neovascularization is a common pathological feature of many ocular vascular diseases, and is an important cause of vision loss in patients. Neovascularization can cause retinal hemorrhage, vitreous he...The formation of neovascularization is a common pathological feature of many ocular vascular diseases, and is an important cause of vision loss in patients. Neovascularization can cause retinal hemorrhage, vitreous hemorrhage, and other serious complications, leading to loss of vision. The treatment of intraocular neovascularization is the focus of ophthalmology research. In recent years, some studies have found that autophagy is closely related to vascular endothelial growth factor and the formation of neovascularization. Autophagy is expected to become a new target for the treatment of intraocular neovascularization. Therefore, this article reviews the research on autophagy and the formation of intraocular neovascularization.展开更多
Objective: To investigate the microR NAs(miR NAs) expression profile of acute myocardial infarction(AMI) rats and the regulating effects of Huoxue Anxin Recipe(活血安心方, HAR) on angiogenesis-related miR NAs a...Objective: To investigate the microR NAs(miR NAs) expression profile of acute myocardial infarction(AMI) rats and the regulating effects of Huoxue Anxin Recipe(活血安心方, HAR) on angiogenesis-related miR NAs and genes. Methods: Forty-five Wistar rats were randomly assigned to 3 groups according to a random number table: sham, AMI, and AMI+HAR groups(15 in each group). AMI rats were established by ligation of the left descending coronary artery. HAR was intragastrically administered to rats of the AMI+HAR group for successive 21 days since modeling, meanwhile the same volume of 0.9% normal saline was administered to rats of the sham and AMI groups. Doppler echocardiography was used for noninvasive cardiac function test. Hematoxylin and eosin staining was used to observe the histopathological change. miR NAs expression profile was detected by quantitative realtime polymerase chain reaction(qR T-PCR). The mR NA and protein expressions of vascular endothelial growth factor(VEGF), and a target gene of miR-210 was further detected by qR T-PCR and Western blot, respectively. The microvessels density of myocardium was evaluated by CD31 immunostaining. Results: Compared with the sham group, ejection fraction(EF) and fractional shortening(FS) values were decreased significantly in the AMI group(P〈0.01), while the infarction area and the interstitial collagen deposition were increased obviously. As for the AMI+HAR group, EF and FS values were increased significantly(P〈0.05 vs. AMI group), and the infarction area was reduced and the interstitial collagen deposition were alleviated significantly. Total of 23 miR NAs in the AMI group expressed differently by at least 1.5 folds compared with those in the sham group; 5 miR NAs in the AMI+HAR group expressed differently by at least 1.5 folds compared with those in the AMI group. Among them, miR-210 was low in the AMI group and high in the AMI+HAR group. The relative mR NA and protein expressions of VEGF were decreased significantly in the AMI group(P〈0.05 vs. sham group), and increased significantly in the AMI+HAR group(P〈0.01 vs. AMI group). CD31 expression area and optical intensity were decreased significantly in the AMI group(P〈0.05 vs. sham group), and increased significantly in the AMI+HAR group(P〈0.01 vs. AMI group). Conclusions: HAR could reduce the infarction area, alleviate the interstitial fibrosis and improve the cardiac function of AMI rats. Those effects could be related to promoting myocardium angiogenesis of HAR by up-regulating miR-210 and VEGF.展开更多
Objectives Little is known about the mechanism of exercise-induced angiogenic response in ischemic myocardium. This study was designed to investigate the effects of exercise training on expression of vascular endothel...Objectives Little is known about the mechanism of exercise-induced angiogenic response in ischemic myocardium. This study was designed to investigate the effects of exercise training on expression of vascular endothelial growth factor and angiogenesis in infarcted heart. Methods Fifty male FVB mice were divided into three subgroups to test various responses to exercise, including time- dependent response of angiogenic factors to exercise training in intact heart (n=10) and infarcted heart (n= 10), as well as exercise-induced angiogenic response in heart with myocardial infarction (MI) (n=30). The mice in the exercise-training groups were allowed to exercise daily at 1 hour per day for 7 days. Results VEGF protein expression was up-regulated by exercise training in time dependent fashion in mice with MI. Angiogenesis was evident by increased myocardial mi- crovessels observed by PECAM-1 immunohistoc-hemi- cal staining in post-MI exercise group (16.5±3.4)/0.4 mm2 versus post-MI sedentary mice (10±2.1)/0.4 mm2 (P < 0.05). Cell proliferation assessment showed significantly higher (P < 0.05 ) number of BrdU positive cells in post MI mice in exercise group as opposed to sedentary post MI mice. 2%TTC staining disclosed a profound difference in the size of MI (18.25±2.93)% in exercise group vs sedentary group (29.26±7.64)% (P< 0.05). Conclusions Activation and up-regulation of VEGF in infarcted mice heart may contributes the angiogenic response to exercise training at the early stage of myocardial infarction. This underscores the impact of exercise on angiogenesis in post myocardial infarction setting.展开更多
Objective To explore whether CD137-CD137L signaling can promote angiogenesis in atherosclerosis plaque via activating nuclear factor of activated T cells c1(NFATc1).Methods Apolipoprotein E knock out mice were divided...Objective To explore whether CD137-CD137L signaling can promote angiogenesis in atherosclerosis plaque via activating nuclear factor of activated T cells c1(NFATc1).Methods Apolipoprotein E knock out mice were divided into the following groups:control group(n=5),CD137 activated group(n=5)and CD137 in-展开更多
Background Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1α and vascular endo...Background Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1α and vascular endothelial growth factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and ascertaining whether HIF-1α and VEGF play important roles in tumor angiogenesis. Methods HIF-1α mRNA expression was analyzed using in situ hybridization and RT-PCR. HIF-1α and VEGF protein were detected in SW480 cells and colorectal adenomas and adenocarcinomas by immunohistochemistry using streptavidin/peroxidase (SP). Western blot was used to detect HIF-1α protein extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas was determined by anti-CD_ 34 immunostaining in colorectal carcinomas. Results Optical density values representing HIF-1α mRNA expression levels were found to be significantly higher in SW480 cells in hypoxic conditions than in cells under normoxic conditions (P<0.05) or in hypoxic conditions but treated with genistein (P<0.05). The levels of HIF-1α and VEGF protein expression in SW480 cells were significantly higher in the hypoxia group than in the normoxia group (P<0.01, P<0.05, respectively) and hypoxia/genistein group (P<0.01, P<0.05, respectively). The positive expression rates of HIF-1α mRNA changed dramatically when comparing colorectal adenomas with adenocarcinomas of different Dukes’ stages (P<0.05). HIF-1α mRNA was also expressed at higher levels in adenocarcinomas than that in adenomas (P<0.01). HIF-1α protein expression correlated significantly with VEGF protein expression and MVD.Conclusions Hypoxia induces the expression of HIF-1α and VEGF in colorectal adenocarcinomas. HIF-1α may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinomas.展开更多
Objective: Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and ...Objective: Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. Data Sources: This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords:"stem cells," "hypoxic preconditioning," "ischemic preconditioning," and "cell transplantation."Study Selection: Original articles and critical reviews on the topics were selected. Results: Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. Conclusions: In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.展开更多
文摘Angiogenesis factor of human osteosarcoma was partially purified and its biological features were studied. The active peptide with 8000 to 10 000 u molecular weight in the conditioned medium obtained from the cultivation of human osteosarcoma cells were partially purified by ultrafiltration, chromatography and dialysis. The angiogenic effects of the fractions were assessed by proliferation assay of human umbilical vein and pig aorta thoracic endothelial cells. The results showed that the chromatography fractions of 4 to 6 could significantly promote the proliferation of the endothelial cells. It was suggested that the human osteosarcoma cells could synthesize and secrete angiogenesis factor with a molecular weight of 8000 to 10 000 u.
文摘Background Hypoxia-inducible factor (HIF) may play an important role in the process of tumorigenesis as well as tumor progression. The aim of this study was to compare the expression between HIF-1α and HIF-2α in tumor angiogenesis and the overall impact on patient prognosis in human non-small cell lung cancer (NSCLC). Methods In the current work we compared the immunohistochemical expression of HIF-1α and HIF-21 in surgical specimens of 140 patients with NSCLC in a tissue microarray study. Relationships between HIF-α expression and clinicopathological or angiogenic factors, including prognosis, were analyzed. Results High HIF-1α and HIF-2α expression was noted in 49/140 (35.0%) and in 64/140 (45.7%) of the cases, respectively. There was no direct correlation between HIF-la and HIF-2α expression. Patients with advanced stage tumors had frequent high expression of HIF-2a (P=0.007), and we also found a significant correlation between HIF-2α and T or N stage (P=0.030 and 0.043, respectively). HIF-1α showed a marginal association with T stage (P=0.084), which showed a higher expression in early stage tumors. A significant correlation (p=0.045) was noticed between HIF-1α and vascular endothelial growth factor (VEGF) expression while the expression levels of thymidine phosphorylase (TP), cyclooxygenase (COX)-2 and microvessel density (MVD) were significantly higher in high HIF-2a tumors (P=0.020, 0.004 and 0.046, respectively). In addition, univariate analysis of overall survival demonstrated that HIF-2a expression, but not HIF-la, was related to poor outcome (P=-0.001) and it retained significant in multivariate analysis (P=0.036). Conclusions Taken together, we conclude that HIF-1α and HIF-2α may differentially regulate the major angiogenic factors in different stages of the tumor process in NSCLC. HIF-2α may play a dominant role in tumor angiogenesis and appears to be of obvious value as a significant prognostic factor in NSCLC.
基金supported by the Fujian Foundation for Distinguished Young Scientists in China,No.Grant#2060203the National Natural Science Foundation of China,No.31070838
文摘We previously showed that the repair of bone defects is regulated by neural and vascular signals. In the present study, we examined the effect of topically applied β-nerve growth factor(β-NGF) on neurogenesis and angiogenesis in critical-sized bone defects filled with collagen bone substitute. We created two symmetrical defects, 2.5 mm in diameter, on either side of the parietal bone of the skull, and filled them with bone substitute. Subcutaneously implanted osmotic pumps were used to infuse 10 μgβ-NGF in PBS(β-NGF + PBS) into the right-hand side defect, and PBS into the left(control) defect, over the 7 days following surgery. Immunohistochemical staining and hematoxylin-eosin staining were carried out at 3, 7, 14, 21 and 28 days postoperatively. On day 7, expression of β III-tubulin was lower on the β-NGF + PBS side than on the control side, and that of neurofilament 160 was greater. On day 14, β III-tubulin and protein gene product 9.5 were greater on the β-NGF + PBS side than on the control side. Vascular endothelial growth factor expression was greater on the experimental side than the control side at 7 days, and vascular endothelial growth factor receptor 2 expression was elevated on days 14 and 21, but lower than control levels on day 28. However, no difference in the number of blood vessels was observed between sides. Our results indicate that topical application of β-NGF promoted neurogenesis, and may modulate angiogenesis by promoting nerve regeneration in collagen bone substitute-filled defects.
文摘BACKGROUND: Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor (VEGF) on inducing angiogenesis following ischemia/reperfusion injury can provide better help for the long-term treatment of cerebrovascular disease in clinic. OBJECTIVE: To observe the effect of VEGF on inducing angiogenesis following focal cerebral ischemia /reperfusion injury in rabbits through the angiogenesis of microvessels reflected by the expression of the factors of vascular pseudohemophilia. DESIGN: A randomized controlled animal tria SETTNG: Department of Medical Imaging, Second Hospital of Hebei Medical University MATERIALS: Sixty-five healthy male New Zealand rabbits of clean degree, weighing (2.6±0.2) kg, aged 4.5-5 months, were used. The polyclonal antibody against vascular pseudohemophilia (Beijing Zhongshan Company), recombinant VEGF165 (Peprotech Company, USA), biotinylated second antibody and ABC compound (Wuhan Boster Company) were applied. METHODS: The experiments were carried out in the Laboratory of Neuromolecular Imaging and Neuropathy, Second Hospital of Hebei Medical University from May to August in 2005. (1) The rabbits were randomly divided into three groups: sham-operated group (n=15), control group (n=25) and VEGF-treated group (n=-25). In the control group and VEGF-treated group, models were established by middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia/reperfusion. In the VEGF-treated group, VEGF165 (2.5 mg/L) was stereotactically injected into the surrounding regions of the infarcted sites immediately after the 2-hour ischemia/reperfusion; Saline of the same dosage was injected in the control group. But the rabbits in the sham-operated group were only drilled but not administrated. (2) The experimental indexes were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment respectively, 3 rabbits in the sham-operated group and 5 in the control group and VEGF-treated group were observed at each time point. The brain tissues in the surrounding regions of the infarcted sites were collected. The positive expressions of the factors of vascular pseudohemophilia in vascular endothelial cells were analyzed with immunohistochemical method. The microvessels in unit statistical field were counted with the imaging analytical software. MAIN OUTCOME MEASURES: The changes of microvascular density in the brain tissue and the positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of the infarcted sites were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment. RESULTS: All the 65 New Zealand rabbits were involved in the analysis of results without deletion. Changes of the number of microvessels at different time points in each group: There were no obvious changes at different time points in the sham-operated group. The numbers of microvessels at 7 and 14 days were obviously more in the control group than in the sham-operated group [(6.0±1.1), (9.0±0.9) microvessels; (3.0±1.1), (3.0±1.1) microvessels; P〈 0.05-0.01], and those at 3, 7, 14 and 28 days were obviously more in the VEGF-treated group than in the control group [(8.3±2.0), (13.4±1.4), (15.5±2.3), (6.8± 1.0) microvessels; (3.4±0.6), (6.0±1.1), (9.0±0.9), (3.2±0.8) microvessels; P 〈 0.01]. (2) Positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of infarcted sites: There were no obvious changes at different time points in the sham-operated group. In the control group, the changing law of the expressions was the same as that for the number of microvessels that the expression began to mildly increase at 7 days, reached the peak value at 14 days, and began to reduce at 28 days. In the VEGF-treated group, the expression was obviously increased at 3 days, also reached the peak value at 14 days, and reduced to the normal level at 70 days, but the expressions were obviously stronger than those in the control group at the same time points. CONCLUSION: Angiogenesis can be obviously induced in rabbits after the focal cerebral ischemia/reperfusion injury is treated with VEGF for 18 days.
文摘Objective: To investigate the relation of vascular endothelial growth factor (VEGF) expression with angiogenesis and cell proliferation in malignant glioma in children. Methods: Immunohistochemical technique was used to detect the expression of VEGF, microvessel quantity (MVQ) and PCNA Labeling Index (PCNA LI) in 33 malignant gliomas in children Results: Positive staining for VEGF was obtained in 23 out of the 33 cases (69.7). The MVQ and PCNA LI in VEFG-positive tumors were significantly higher than those in VEGF-negative tumors (P<0.005). The expression of VEGF in tumor tissues was significantly correlative with MVQ and PCNA LI (r=0.52 and 0.37, respectively, P<0.001). Conclusion: VEGF can be synthesized in tumor cells of malignant glioma in children which might play a significant role in angiogenesis and cell proliferation in the tumor.
文摘BACKGROUND: In the process of vascularization, vascular endothelial growth factor (VEGF), angiopoietin-2 and Tie2 are involved in the migration, differentiation and proliferation of vascular endothelial cells, and stimulate the rapid angiogenesis; Tiel and angiopoietin-1 play important roles in facilitating the formation of vascular lumen and maintaining the integrity of vascular wall. Thus the distributions and expressions may be associated with the occurrence of cerebral arteriovenous malformation. OBJECTIVE: To observe the biological effects of angiogenic factors in the occurrence and development of cerebral arteriovenous malformation. DESIGN: An observational comparative experiment. SETTINGS: Department of Neurosurgery, General Hospital of Shenyang Military Area Command of Chinese PLA; Department of Neurosurgery, General Hospital of Tianjin Medical University. PARTICIPANTS: Fresh samples of complete cerebral arteriovenous malformations resected in 47 patients were collected from the Department of Neurosurgery, General Hospital of Tianjin Medical University from August 1999 to May 2001, including 22 males and 25 females, the mean age was 34.5 years. Informed consents were obtained from all the patients or their relatives. The initial symptom was hemorrhage in 28 cases. All the patients were classified according to the clinical imaging data and Spetzler-Martin grading standard, including 11 cases of grade Ⅰ, 17 cases of grade Ⅱ, 11 cases of grade Ⅲ, and 8 cases of grade Ⅳ - Ⅴ. Normal brain tissues resected by decompression due to trauma were taken from 8 patients as controls, including 5 males and 3 females, aging 12 - 65 years. METHODS: ① The expressions of VEGF, Tie receptors, angiopoietin-1, angiopoietin-2, proto-oncogene c-myc and proliferating cell nuclear antigen(PCNA) in the samples of cerebral arteriovenous malformation were detected with immunohistochemical method. Under light microscope, the positively stained rat-anti-human factor Ⅷ-related antigens (specific marker of vascular endothelial cells) were counted, then the immuno-positive cells of the other antibodies in the visual field of neighboring section which was in "mirror" relation were counted, and the percentage of the latter to the former was considered as the labeling index of positive cells. The immunostaining intensity was classified negative ( - ): no positive cells; positive (+): number of positive cells 〈 20%; moderately positive (++): number of positive cells 20% - 50%; strongly positive (+++): number of positive cells 〉 50%. ② The differences of the enumeration data were compared with chi-squam test, and the correlation were analyzed with the linear correlation analysis. MAIN OUTCOME MEASURES: Expressions and distributions of VEGF, Tie 1 and Tie2 receptors, angiopoietin-1, angiopoietin-2, PCNA and c-myc in the samples of cerebral arteriovenons malformation and normal brain tissue. RESULTS: ① Expressions of angiogenic factors in the control group and cerebral arteriovenons malformation groups of each grade: The positive rates of VEGF, Tie2, angiopoietin-2, c-myc and PCNA expressions in the control group were significantly different from those in the cerebral arteriovenous malformation groups of each grade ( x^2=21.09 - 34.23, P 〈 0.05), whereas the positive rates of Tiel and angiopoietin-1 expressions were close ( x^2=3.43 - 3.869, P 〉 0.05). ② Expressions of angiogenic factors in hemorrhage group and non-hemorrhage group: The expressions of VEGF, angiopoietin-2 and PCNA in the hemorrhage group were significantly lower than those in the non-hemorrhage group ( x^2= 16.22 - 26.56, P 〈 0.05). There ware no obvious differences in the expressions of Tiel and angiopoietin-1 expressions between the hemorrhage group and non-hemorrhage group ( x^2=3.22 - 3.78, P 〉 0.05).The VEGF was positively correlated with the expressions of c-myc and PCNA (r = 0.728, 0.916, P 〈 0.05). CONCLUSION: ①The expressions of angiogenic factors and related receptors may be involved in the process of cerebral arteriovenous malformation, and had important correlation the its clinical grading. ② Angiogenic factors may induce the expression of endothelial cell c-myc in cerebral arteriovenous malformation, and then interfere the cell proliferation and apoptosis.
基金financially supported by the National Natural Science Foundation of China,No.81072799
文摘Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury,but the underlying mechanisms remain unclear.In this study,rats were intragastrically given Buyanghuanwu decoction,15 m L/kg,for 3 days.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.In rats administered Buyanghuanwu decoction,infarct volume was reduced,serum vascular endothelial growth factor and integrin αvβ3 levels were increased,and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals.These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor(administered through the lateral ventricle for 7 consecutive days).These data suggest that Buyanghuanwu decoction promotes angiogenesis,improves cerebral circulation,and enhances brain tissue repair after cerebral ischemia/reperfusion injury.
基金This work was supported by the Natural Science Foundation of Beijing (No. 953307900).
文摘To study the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in esophageal squamous cell carcinoma (ESCC) and clarify the association of VEGF expression with the angiogenesis and prognostic value of this disease. Methods: Eighty-two cases with primary ESCC treated with radical operation in Department of Surgery from Jan 1981 through May 1994 were enrolled. VEGF expression and MVD value were examined by immunohistochemical staining, the streptavidin-biotin peroxidase complex method (SP method), using anti-VEGF polyclonal antibody and anti-Factor-VIII antibody, respectively. We also analyzed the relationship between VEGF expression and MVD value and postoperative survival rate of patients. Results: Of the 82 cases, 63.4% cases showed positive for VEGF in tumor cells and the median of MVD in tumor was 37 (9-150)·mm-2. There was a close correlation between MVD and VEGF (P=0.001). The 5-year survival rate of patients with low and high MVD was 34.1% and 12.2%, respectively. The 5-year survival rate was 46.7% in patients with VEGF-negative tumor and 11.5% in patients with VEGF-positive tumor. These differences were statistically significant (P=0.017 and P<0.001, respectively). Conclusion: In ESCC, angiogenesis is mediated mainly by VEGF and VEGF may be associated with tumor progression and increased malignancy via angiogenesis.
基金The research was supported by the fund for the Top Talents Award Plan of Yangzhou University(2020)the Cyanine Project of Yangzhou University(2020).
文摘This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to110 of gestation with either rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)on placental amino acid(AA)transport,angiogenic gene expression,and steroid anabolism.On d 35 of gestation,32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups,each consisting of eight ewes,and were fed the following diets:A diet providing 100%of NRC’s nutrient requirements for pregnant ewes(CON);A diet providing 50%of NRC’s nutrient requirements for pregnant ewes(RES);RES diet plus 5 g/d NCG(RES+NCG);or RES diet plus 20 g/d RP-Arg(RES+ARG).On the d 110 of pregnancy,blood samples were taken from the mother,and samples were collected from type A cotyledons(COT;the fetal portions of the placenta).The levels of 17β-estradiol and progesterone in the maternal serum and both the capillary area density(CAD)and capillary surface density(CSD)in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group.The concentrations of arginine,leucine,putrescine and spermidine in type A COT were higher(P<0.05)in the RES+ARG or RES+NCG group than in the RES group.The mRNA expression levels of inducible nitric oxide synthase(iNOS)and solute carrier family 15,member 1(SLC15A1)were increased(P<0.05)while those of progesterone receptor(PGR)and fibroblast growth factor 2(FGF2)were decreased in type A COT by supplementation with either NCG or RP-Arg compared to the RES group.The results suggest that providing underfed pregnant ewes from d 35 to 110 of gestation with a diet supplemented with NCG or RP-Arg improves placental AA transport,and reduces the expression of angiogenic growth factor genes and steroid anabolism,leading to better fetal development.
基金Supported by the Natural Science Foundation of Shaanxi province(No.2016JM8018)the Natural Science Foundation of Xi’an Science Technology Bureau[(No.SF1508(3)]
文摘The formation of neovascularization is a common pathological feature of many ocular vascular diseases, and is an important cause of vision loss in patients. Neovascularization can cause retinal hemorrhage, vitreous hemorrhage, and other serious complications, leading to loss of vision. The treatment of intraocular neovascularization is the focus of ophthalmology research. In recent years, some studies have found that autophagy is closely related to vascular endothelial growth factor and the formation of neovascularization. Autophagy is expected to become a new target for the treatment of intraocular neovascularization. Therefore, this article reviews the research on autophagy and the formation of intraocular neovascularization.
基金Supported by the Major New Drug Development Program from the Ministry of Science and Technology,China(No.2012ZX09102-201-006)
文摘Objective: To investigate the microR NAs(miR NAs) expression profile of acute myocardial infarction(AMI) rats and the regulating effects of Huoxue Anxin Recipe(活血安心方, HAR) on angiogenesis-related miR NAs and genes. Methods: Forty-five Wistar rats were randomly assigned to 3 groups according to a random number table: sham, AMI, and AMI+HAR groups(15 in each group). AMI rats were established by ligation of the left descending coronary artery. HAR was intragastrically administered to rats of the AMI+HAR group for successive 21 days since modeling, meanwhile the same volume of 0.9% normal saline was administered to rats of the sham and AMI groups. Doppler echocardiography was used for noninvasive cardiac function test. Hematoxylin and eosin staining was used to observe the histopathological change. miR NAs expression profile was detected by quantitative realtime polymerase chain reaction(qR T-PCR). The mR NA and protein expressions of vascular endothelial growth factor(VEGF), and a target gene of miR-210 was further detected by qR T-PCR and Western blot, respectively. The microvessels density of myocardium was evaluated by CD31 immunostaining. Results: Compared with the sham group, ejection fraction(EF) and fractional shortening(FS) values were decreased significantly in the AMI group(P〈0.01), while the infarction area and the interstitial collagen deposition were increased obviously. As for the AMI+HAR group, EF and FS values were increased significantly(P〈0.05 vs. AMI group), and the infarction area was reduced and the interstitial collagen deposition were alleviated significantly. Total of 23 miR NAs in the AMI group expressed differently by at least 1.5 folds compared with those in the sham group; 5 miR NAs in the AMI+HAR group expressed differently by at least 1.5 folds compared with those in the AMI group. Among them, miR-210 was low in the AMI group and high in the AMI+HAR group. The relative mR NA and protein expressions of VEGF were decreased significantly in the AMI group(P〈0.05 vs. sham group), and increased significantly in the AMI+HAR group(P〈0.01 vs. AMI group). CD31 expression area and optical intensity were decreased significantly in the AMI group(P〈0.05 vs. sham group), and increased significantly in the AMI+HAR group(P〈0.01 vs. AMI group). Conclusions: HAR could reduce the infarction area, alleviate the interstitial fibrosis and improve the cardiac function of AMI rats. Those effects could be related to promoting myocardium angiogenesis of HAR by up-regulating miR-210 and VEGF.
文摘Objectives Little is known about the mechanism of exercise-induced angiogenic response in ischemic myocardium. This study was designed to investigate the effects of exercise training on expression of vascular endothelial growth factor and angiogenesis in infarcted heart. Methods Fifty male FVB mice were divided into three subgroups to test various responses to exercise, including time- dependent response of angiogenic factors to exercise training in intact heart (n=10) and infarcted heart (n= 10), as well as exercise-induced angiogenic response in heart with myocardial infarction (MI) (n=30). The mice in the exercise-training groups were allowed to exercise daily at 1 hour per day for 7 days. Results VEGF protein expression was up-regulated by exercise training in time dependent fashion in mice with MI. Angiogenesis was evident by increased myocardial mi- crovessels observed by PECAM-1 immunohistoc-hemi- cal staining in post-MI exercise group (16.5±3.4)/0.4 mm2 versus post-MI sedentary mice (10±2.1)/0.4 mm2 (P < 0.05). Cell proliferation assessment showed significantly higher (P < 0.05 ) number of BrdU positive cells in post MI mice in exercise group as opposed to sedentary post MI mice. 2%TTC staining disclosed a profound difference in the size of MI (18.25±2.93)% in exercise group vs sedentary group (29.26±7.64)% (P< 0.05). Conclusions Activation and up-regulation of VEGF in infarcted mice heart may contributes the angiogenic response to exercise training at the early stage of myocardial infarction. This underscores the impact of exercise on angiogenesis in post myocardial infarction setting.
文摘Objective To explore whether CD137-CD137L signaling can promote angiogenesis in atherosclerosis plaque via activating nuclear factor of activated T cells c1(NFATc1).Methods Apolipoprotein E knock out mice were divided into the following groups:control group(n=5),CD137 activated group(n=5)and CD137 in-
基金ThisstudywassupportedbytheFundforKeyTechnologiesRandDProgrammeofHubeiProvince (No 2 0 0 3AA3 0 1CO3 )
文摘Background Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1α and vascular endothelial growth factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and ascertaining whether HIF-1α and VEGF play important roles in tumor angiogenesis. Methods HIF-1α mRNA expression was analyzed using in situ hybridization and RT-PCR. HIF-1α and VEGF protein were detected in SW480 cells and colorectal adenomas and adenocarcinomas by immunohistochemistry using streptavidin/peroxidase (SP). Western blot was used to detect HIF-1α protein extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas was determined by anti-CD_ 34 immunostaining in colorectal carcinomas. Results Optical density values representing HIF-1α mRNA expression levels were found to be significantly higher in SW480 cells in hypoxic conditions than in cells under normoxic conditions (P<0.05) or in hypoxic conditions but treated with genistein (P<0.05). The levels of HIF-1α and VEGF protein expression in SW480 cells were significantly higher in the hypoxia group than in the normoxia group (P<0.01, P<0.05, respectively) and hypoxia/genistein group (P<0.01, P<0.05, respectively). The positive expression rates of HIF-1α mRNA changed dramatically when comparing colorectal adenomas with adenocarcinomas of different Dukes’ stages (P<0.05). HIF-1α mRNA was also expressed at higher levels in adenocarcinomas than that in adenomas (P<0.01). HIF-1α protein expression correlated significantly with VEGF protein expression and MVD.Conclusions Hypoxia induces the expression of HIF-1α and VEGF in colorectal adenocarcinomas. HIF-1α may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinomas.
文摘Objective: Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. Data Sources: This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords:"stem cells," "hypoxic preconditioning," "ischemic preconditioning," and "cell transplantation."Study Selection: Original articles and critical reviews on the topics were selected. Results: Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. Conclusions: In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.