Esophageal cancer is one of the common malignant tumors with high incidence and poor prognosis. Angiogenesis-related pathways play an important role in the occurrence and development of esophageal cancer. Vascular endothelial growth factor (VEGF) is the main mediator of angiogenesis. In addition to promoting angiogenesis and maintaining the survival of neovascularization, VEGF can also directly act on esophageal cancer cells and promote the occurrence and development of tumors. This article reviews the biology of VEGF and its effect on blood vessels, the expression of VEGF in esophageal cancer cells and its influencing factors, the role of VEGF in esophageal cancer cells, the immunomodulatory activity of VEGF and the clinical study of VEGF inhibitors. The purpose of this study is to provide a basis for more rational use of VEGF inhibitors in the treatment of esophageal cancer.
ObjectiveTo observe and analyze the influencing factors for the prognosis of anti-vascular endothelial growth factor (VEGF) drug treatment in patients with macular neovascularization (MNV) under 45 years old. MethodsA retrospective clinical case study. A total of 89 MNV patients with 96 eyes who were diagnosed and treated with anti-VEGF drugs in Department of Ophthalmology of The Second Hospital of Lanzhou University from January 2020 to January 2024 were included in the study. The ages of all patients were ＜45 years old. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations; 49 eyes underwent OCT angiography (OCTA) examination. The BCVA examination was carried out using the international standard visual acuity chart and was converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity for statistics. The macular foveal thickness (CMT) was measured using an OCT instrument. The size of the MNV lesion was measured using the software of the OCTA self-contained device. The affected eyes were given intravitreal injection of anti-VEGF drugs once, and then the drugs were administered as needed after evaluation. The follow-up time after treatment was ≥6 months. During the follow-up, relevant examinations were performed using the same equipment and methods as before treatment. The last follow-up was taken as the time point for efficacy evaluation. According to the OCT image characteristics of the MNV lesions, the affected eyes were divided into the fibrous scar group and the non-fibrous scar group, with 52 (54.16%, 52/96) and 44 (45.83%, 44/96) eyes respectively. Comparing the CMT and BCVA at the last follow-up with those at the baseline, the affected eyes were divided into the CMT reduction group, the CMT increase group, the BCVA improvement group and the BCVA reduction group, with 66 (68.75%, 66/96), 30 (31.25%, 30/96) eyes and 74 (77.08%, 74/96), 22 (22.92%, 22/96) eyes respectively. The Mann-Whitney U test was used for the comparison of non-normally distributed measurement data between groups. Logistic regression analysis was used to analyze the independent factors affecting the prognosis of MNV patients. ResultsThere were no statistically significant differences in the age (Z=?0.928) and gender composition ratio (χ2= 0.123) between the fibrous scar group and the non-fibrous scar group (P＞0.05); there were statistically significant differences in the number of eyes with a follow-up time of ≥36 months and ＜36 months (χ2= 3.906, P=0.048); there were statistically significant differences in the size of the MNV lesions (Z=?2.385, P=0.017); there were statistically significant differences in the number of eyes with different vascular network morphologies (χ2=12.936, P=0.001). Before treatment and at the last follow-up, the CMT of the affected eyes was 267.50 (237.25, 311.75) μm and 242.00 (217.25, 275.75) μm respectively; logMAR BCVA was 0.20 (0.10, 0.50) and 0.35 (0.16, 0.60) logMAR respectively. There were statistically significant differences in the CMT and logMAR BCVA before treatment and at the last follow-up (Z=?3.311,?1.984; P=0.001, 0.047). There were statistically significant differences in different ages (Z=?2.284), myopic diopter (χ2=7.437), etiology (χ2=6.956), and disease course (Z=?1.687) between the CMT reduction group and the CMT increase group (P＜0.05). There were statistically significant differences in the number of eyes with different subjective feelings between the BCVA improvement group and the BCVA reduction group (χ2=10.133, P＜0.05). The results of logistic regression analysis showed that the etiology was an independent risk factor for CMT thickening. ConclusionsAge, etiology, myopic diopter, disease course, follow-up time, lesion size and the morphology of the neovascular network are the influencing factors for the prognosis of anti-VEGF drug treatment in MNV patients under 45 years old. The etiology is an independent risk factor for CMT increase.
Objective
To investigate the effects of human insulin-like growth factor 1 (hIGF-1) gene transfected by recombinant adenovirus vector (Ad-hIGF-1) on the apoptosis of rabbit nucleus pulposus cells induced by tumor necrosis factor α (TNF-α).
Methods
The intervertebral disc nucleus pulposus were harvested from 8 healthy adult domestic rabbits (male or female, weighing 2.0-2.5 kg). The nucleus pulposus cells were isolated with collagenase II digestion and the passage 2 cells were cultured to logarithm growing period, and then they were divided into 3 groups according to culture condition: DMEM/F12 medium containing 10% PBS, DMEM/F12 medium containing 10% PBS and 100 ng/mL TNF-α, and DMEM/ F12 medium containing 10% PBS, 100 ng/ mL TNF-α, and Ad-hIGF-1 (multiplicity of infection of 50) were used in control group, TNF-α group, and Ad-hIGF-1 group, respectively. The results of transfection by adenovirus vector carrying hIGF-1 gene were observed by fluorescent microscopy; the expression of hIGF-1 protein was detected by Western blot, hIGF-1 mRNA expression by RT-PCR, and the cell apoptosis rate by TUNEL and flow cytometry.
Results
Green fluorescence was observed by fluorescent microscopy in Ad-hIGF-1 group, indicating that successful cell transfection. The expressions of hIGF-1 protein and mRNA were detected in Ad-hIGF-1 group by Western blot and RT-PCR, while the control group and TNF-α group had no expression. The cell apoptosis rates of TNF-α group, Ad-hIGF-1 group, and control group were 34.24% ± 4.60%, 6.59% ± 1.03%, and 0.40% ± 0.15%, respectively. The early apoptosis rates of TNF-α group, Ad-hIGF-1 group, and control group were 22.16% ± 2.69%, 5.03% ± 0.96%, and 0.49% ± 0.05%, respectively; the late cell apoptosis rates were 13.96% ± 4.86%, 10.68% ± 3.42%, and 0.29% ± 0.06%, respectively. Compared with TNF-α group, the cell apoptosis rates of Ad-hIGF-1 group and control group were significantly reduced (P lt; 0.05); the cell apoptosis rate of Ad-hIGF-1 group was significantly higher than that of control group (P lt; 0.05).
Conclusion
Ad-hIGF-1 could inhibit the apoptosis of nucleus pulposus cells induced by TNF-α.
【Abstract】 Objective Sonic hedgehog (Shh) signaling pathway is involved in an important part of regulating angiogenesis. To investigate the effects of recombinant Shh N-terminant (rShh-N) on the expression and secretion of angiogenesis-related factor—vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Methods Bone marrow mesenchymal stem scells (BMSCs) were isolated from 3-day-old healthy Sprague Dawley rats and cultured to passage 3 in vitro. rShh-N at the concentrations of 0, 10, 100, and 200 ng/mL were applied to culture BMSCs in groups A, B, C, and D, respectively. At 12, 24, 48, and 72 hours of culture, the expressions of VEGF and bFGF mRNA and the levels of VEGF and bFGF in supernatant were measured with real-time quantitative PCR and ELISA, respectively. Results At the gene level, compared with group A, the expressions of VEGF and bFGF mRNA were enhanced in group D (P lt; 0.05) and the upregulation was more significant at 12 and 48 hours than 24 and 72 hours (P lt; 0.01). In group C, bFGF mRNA expression was substantially promoted at 12-72 hours (P lt; 0.05) and VEGF mRNA level was upregulated at 24-72 hours (P lt; 0.05), and both reached peak at 72 hours (P lt; 0.01). In group B, VEGF mRNA expression was inhibited at 12 hours (P lt; 0.05), but the level increased at 48 and 72 hours (P lt; 0.05); bFGF mRNA expression was obviously promoted at 12-48 hours (P lt; 0.05) and the maximum appeared at 48 hours (P lt; 0.01). At the protein level, the secretion of VEGF and bFGF in group D was significantly increased at 12-72 hours, as compared with group A (P lt; 0.05). In group C, VEGF and bFGF secretion was increased at 24-72 hours (P lt; 0.05). The secretion of VEGF in group B was inhibited at 12 and 48 hours (P lt; 0.05) and was promoted at 24 hours (P lt; 0.05); bFGF secretion was up-regulated at 24 and 48 hours (P lt; 0.05). The secretion of VEGF and bFGF in supernatant at 【Abstract】 Objective Sonic hedgehog (Shh) signaling pathway is involved in an important part of regulating angiogenesis. To investigate the effects of recombinant Shh N-terminant (rShh-N) on the expression and secretion of angiogenesis-related factor—vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Methods Bone marrow mesenchymal stem scells (BMSCs) were isolated from 3-day-old healthy Sprague Dawley rats and cultured to passage 3 in vitro. rShh-N at the concentrations of 0, 10, 100, and 200 ng/mL were applied to culture BMSCs in groups A, B, C, and D, respectively. At 12, 24, 48, and 72 hours of culture, the expressions of VEGF and bFGF mRNA and the levels of VEGF and bFGF in supernatant were measured with real-time quantitative PCR and ELISA, respectively. Results At the gene level, compared with group A, the expressions of VEGF and bFGF mRNA were enhanced in group D (P lt; 0.05) and the upregulation was more significant at 12 and 48 hours than 24 and 72 hours (P lt; 0.01). In group C, bFGF mRNA expression was substantially promoted at 12-72 hours (P lt; 0.05) and VEGF mRNA level was upregulated at 24-72 hours (P lt; 0.05), and both reached peak at 72 hours (P lt; 0.01). In group B, VEGF mRNA expression was inhibited at 12 hours (P lt; 0.05), but the level increased at 48 and 72 hours (P lt; 0.05); bFGF mRNA expression was obviously promoted at 12-48 hours (P lt; 0.05) and the maximum appeared at 48 hours (P lt; 0.01). At the protein level, the secretion of VEGF and bFGF in group D was significantly increased at 12-72 hours, as compared with group A (P lt; 0.05). In group C, VEGF and bFGF secretion was increased at 24-72 hours (P lt; 0.05). The secretion of VEGF in group B was inhibited at 12 and 48 hours (P lt; 0.05) and was promoted at 24 hours (P lt; 0.05); bFGF secretion was up-regulated at 24 and 48 hours (P lt; 0.05). The secretion of VEGF and bFGF in supernatant at
OBJECTIVE: To study the stimulating effects of basic fibroblast growth factor(bFGF) on fibroblast function and its ability to expression of c-fos gene. Furthermore, to explore the possible network action between bFGF and oncogene in modulating wound healing. METHODS: Cultured rat fibroblasts were divided into bFGF stimulating group and control group. Fibroblasts in bFGF stimulating group were treated with bFGF in a dosage of 40 ng/culture hole, while the control fibroblasts were treated with the same vehicle without bFGF. The morphology, cell vitality and their ability to express c-fos gene in the fibroblasts in both groups were studied with MTT and immunohistochemical methods. RESULTS: All fibroblasts in bFGF treated groups were enlarged and showed increased vitality with MTT method. C-fos gene expression in bFGF stimulating group was increased, especially in nucleus when compared with those in control group. CONCLUSION: The results show that the function and the ability to express c-fos gene in bFGF treated fibroblasts are enhanced. Combined with our previous studies, it may make a conclusion that there is a network regulation mechanism between growth factors and some oncogenes.
Objective To observe the effects of immunologic cytokines or anti-angiogenesis gene transfer mediated by electroporation for choroidal melanoma cells.Methods The human embryo kidney cells and malignant choroidal melanoma cells were transfected with plasmids pNGVL-mIL2, pNGVL-mIL12, pCI-sFLK-1, pCR3.1-antiVEGF121,pCI-ExTek. Then the expression of mIL2, mIL12, sFLK-1, VEGF and ExTek were detected by enzymelinked immunosorbentassay (ELISA) and Western blot. Nude mice models of malignant choroidal melanoma were established and they were divided into four groups randomly. Each group was treated with 30 mu;l of 0.9% NaCl, 30 mu;g pNGVL, 30 mu;g antiVEGF121+sFLK-1+ExTek and 30 mu;g mIL2+mIL12 respectively by electroporation. Seven，14, 21, 28, 35 and 42 days after treatment, the tumor volumes were measured to calculate the tumor inhibition rate. Results ELISA and Western blot showed that mIL2，mIL12，sFLK-1 and ExTek were expressed after electroporation，VEGF expression was decreased remarkably. After treatment，the tumors of mIL2+mIL12 group were greatly inhibited with a tumor inhibition rate of 97.33%，while the tumors of antiVEGF121+sFLK-1+ExTek and pNGVL group were partially inhibited with tumor inhibition rates of 53.33% and 36.33% respectively.Conclusions Immunologic cytokines transfer mediated by electroporation can inhibit the growth of melanoma，but anti-angiogenesis only have a mild effects.
ObjectiveTo explore the expression of vascular endothelial growth factor receptor-2(VEGFR-2) protein in esophageal squamous cell carcinoma (ESCC) and to analyze the relationship between VEGFR-2 and prognostic of esophageal cancer in Uygur of Xinjiang.
MethodsThe expression of VEGFR-2 protein including 72 patients with ESCC[with 56 males and 16 females at age of 57 (43-79) years] and paracarcinomatous tissues of 28 patients were detected by immunohistochemistry staining (SP) between January 2007 and september 2009 in this hospital. The Kaplan-Meier and Cox proportional hazards analysis were used to analyze the prognosis of ESCC.
ResultsThe positive expression rate of VEGFR-2 protein in 72 patients with ESCC was 80.56% (58/72) and 0 in paracarcinomatous tissues. The expression of VEGFR-2 protein in the ESCC was much higher than that in paracarcinomatous tissues with a statistical difference (P<0.05). The expression of VEGFR-2 protein was significantly correlated with depth of invasion, lymph node metastasis, distant metastasis and TNM staging (P<0.05). Tumor size was no correlation with expression of VEGFR-2 protein (P>0.05). Kaplan-Meier survival analysis indicated that five-year survival rate in positive expression of VEGFR-2 was higher than that in the negative group. Lymph node metastasis, TNM staging, and the positive expression of VEGFR-2 protein were independent prognostic factors.
ConclusionVEGFR-2 protein is expressed more in ESCC and might be used as the index to predict prognosis and metastasis of esophagedal carcinoma in Uygur.
Abstract For the purpose of studying the effects on wound healing of three new bioelectret composites (BC) which are composed ofcollagen polyvinyl alcohol and epidermal growth factor (EGF), 30 rabbits were divided into 5 groups. Three wounds in round shape (1.8 cm in diameter) were made in each side of the back of the rabbits. The wounds of 1～3 groups were treated by one of the three BC respectively, group 4 treated by SDAg, and group 5 were treated by Normal saline as control. From observation of the growth of the granulation tissue, the reepithelization and the pathological assessment, it was shown that the quality of wound healing in all BC treated wounds was better than that in SDAg or the control. It indicated that the BC benefited the wound healing, and this might also be due to its bioelectric effects and the direct effects from growth factor.
Objective To observe the effects of stromal cellderived factor 1alpha; (SDF-1alpha;) in secondary neovascular glaucoma (NVG) of proliferative diabetic retinopathy (PDR). Methods The vitreous specimens from 25 PDR patients (31 eyes) were collected with 13 NVG eyes and non-NVG 18 eyes. The concentrations of SDF-1alpha; and vascular endothelial growth factor (VEGF) in those specimens were measured by enzyme-linked immunosorbent assay （ELISA）. Human umbilical vein endothelial cells (HUVEC) were treated by different concentrations of SDF-1alpha;and vascular endothelial growth factor (VEGF) in vitro, and the formation of tube cavity-like structure, length of capillarylike structures and 5prime;-bromo-2prime;-deoxyuridine (BrdU) labeling of treated HUVEC were measured. Results The length of HUVEC tube-like and capillarylike structure formation in 10, 100, 1000 ng/ml SDF-1alpha; and 10 ng/ml VEGF groups were longer than that in the control group, the differences were statistically significant (P＜0.01). The A value of BrdU labeling of 10, 100, 1000 ng/ml SDF-1alpha; and 10 ng/ml VEGF groups were increased than that in the control group, the differences were statistically significant (P＜0.01). The vitreous levels of SDF-1alpha; and VEGF of NVG specimens were higher than those in the non-NVG group, the differences were statistically significant (P＜0.01). Conclusions SDF-1alpha; may promote the migration and proliferation of vascular endothelium cells, and participate in the neovascularization process in NVG patients with PDR.
OBJECTIVE: To explore the expression of alpha-smooth muscle actin (alpha-SMA) induced by transforming growth factor beta 1 (TGF-beta 1). METHODS: Five samples of hypertrophic scars and three samples of normal mature scars were collected as the experimental and control groups respectively. The fibroblasts were isolated from scars, and cultured in 2-dimension or 3-dimension culture system. The immunohistochemical staining method of LSAB were used to investigate the expression of alpha-SMA in fibroblasts in the different concentration of TGF-beta 1. RESULTS: The expression of alpha-SMA in 3-dimension culture system were markedly lower than those in 2-dimension culture system with respect to the fibroblasts in the experimental group. The expression of alpha-SMA in fibroblasts were different in response to various TGF-beta 1 concentration, it was more effective at the concentration of 5 ng/ml. The expression of alpha-SMA in the fibroblasts from hypertrophic scars seemed to be more sensitive to TGF-beta 1 compared to that of the normal mature scars. CONCLUSION: There are concentration-dependent in the expression of alpha-SMA induced by TGF-beta 1 in scar fibroblasts in vitro. The biological characteristics of the fibroblasts from hypertrophic scars and normal mature scars and their sensitivity to the inducement of TGF-beta 1 were different. The inducement of TGF-beta 1 may be depressed by extracellular matrix components and that may decrease the expression of alpha-SMA.
