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Objective:To explore the prediction model of tissue chip technology for the chemotherapy response of patients with colorectal cancer.Methods:217 patients with colorectal cancer who had received standardized chemotherapy in the Affiliated People’s Hospital of Ningbo University from Jan. 2017 to Dec. 2019 were prospectively selected. The patients were randomly divided into training set (152 cases) and test set (65 cases) according to the ratio of 7:3, and were followed up for 6 months. The clinical data of the patients in the training set were compared, the expression levels of Ang-2, caspase-3 and CD147 in the patients were analyzed by tissue microarray technology, and the related factors affecting the responsiveness of colorectal cancer chemotherapy were analyzed by the Logistic regression model. R software was used based on the training set. A nomogram prediction model was built and model performance on the test set was evaluated.Results:One case was excluded from the training center, and 151 cases were finally included, including 93 cases in the chemotherapy response group and 58 cases in the chemotherapy response group. The tumor diameter, serum carcinoembryonic antigen, caspase3, Ang2 expression level, and the proportion of clinical stage IV in the poor chemotherapy group were significantly higher than those in the good chemotherapy group (all P<0.05) ; Logistic regression showed tumor diameter ( OR=2.394), serum carcinoembryonic antigen ( OR=1.878), caspase-3 ( OR=4.261), Ang-2 expression level ( OR=5.457), and clinical stage IV ( OR=5.954) were independent risk factors for adverse drug reactions in patients with colorectal cancer (all P<0.05). The consistency index (C-index) for predicting the factors related to adverse chemotherapy reactions in patients with colorectal cancer was 0.915. External verification showed that the sensitivity was 86.96%, the specificity was 92.50%, and the accuracy was 90.48% (42/65) . Conclusion:The expression levels of Ang-2 and caspase-3 are correlated with the responsiveness of colorectal cancer to chemotherapy, and can be used as predictive indicators to evaluate the responsiveness of colorectal cancer to chemotherapy.
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Diabetic macular edema(DME)and age-related macular degeneration(ARMD)are the leading causes of visual impairment and blindness worldwide, and their common pathological features are increased vascular permeability and abnormal neovascularization, in which cytokines such as vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)play an important role. Intravitreal injection of anti-VEGF agents significantly changed the clinical management of DME and ARMD, but limitations such as the non-responsive cases, the treatment burden and risks caused by frequent injections need to be overcome. Faricimab, a novel bispecific monoclonal antibody that simultaneously targets VEGF-A and Ang-2, can effectively reduce vascular permeability, decrease the number of neovascularization and alleviate retinal edema. Registered clinical studies have shown that Faricimab is effective in improving vision and reducing retinal edema, which is non-inferior to Aflibercept and Ranibizumab, maintains a long dosing interval, and has a high safety profile. This article reviews the latest advances in the treatment of DME and ARMD with Faricimab.
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Objective: To study the effect and mechanism of Angelica dahurica extract (AD) on neovascularization maturation in db/db mice. Methods: Forty-eight 8-week-old male db/db mice were randomly divided into model group and A. dahurica extract-treated group, and 24 littermate male db/m mice were set as control group. A mouse model of diabetic ulcer was prepared by punching the back. The A. dahuricae extract-treated group was administered with AD 1.8 g/kg ig, and control group and model group were ig administered with the same amount of normal saline for 21 d. The healing condition of mouse wounds was recorded at 2, 4, 7, 11, 14 and 21 d after trauma. The number and maturation of new blood vessels in wound tissues was observed by HE, immunohistochemistry and immunofluorescence staining at 11 d after trauma. Expression of fork head transcription factor (FOXO1) and angiopoietin-2 (Ang-2) in wound tissues were detected by Western blotting and immunohistochemistry. According to different intervention conditions in vitro, endothelial cells were divided into normal glucose and hypoxia group, high glucose and hypoxia group, hypertonic and hypoxic group, high glucose and hypoxia + A. dahurica extract-treated group. Endothelial cells were co-cultured with pericytes under different intervention conditions, and the effects of A. dahurica intervention on endothelial cells' chemotaxis and tubular structure formation in vitro under high glucose and hypoxia were observed. Western blotting was used to detect the levels of FOXO1, p-FOXO1 and Ang-2 proteins and their upstream protein kinase B (Akt) and phosphorylation protein changes in wound tissues and endothelial cells. Results: The wound healing rate of the A. dahurica extract-treated group, the general recovery of the wound, the number of blood vessels and the maturation of new blood vessels in the wound tissue were significantly better than the model group (P < 0.05). FOXO1 and Ang-2 protein expression levels in the A. dahurica extract-treated group were significantly higher than the model group (P < 0.05); p-Akt and p-FOXO1 protein expression in the A. dahurica extract-treated group were lower than model group (P < 0.05). After A. dahurica intervention in endothelial cells under high glucose and hypoxia in vitro, the expression levels of FOXO1 and Ang-2 protein in the cells were significantly reduced (P < 0.05), p-Akt and p-FOXO1 protein expression were significantly increased (P < 0.05); In addition, A. dahurica extract could increase the chemotaxis of endothelial cells to pericytes under high glucose and hypoxia and promote the formation of tubular structures of endothelial cells and pericytes in vitro under high glucose and hypoxia. Conclusion: A. dahurica extract can promote the formation and maturation of neovascularization, so as to improve the rate and quality of wound healing in db/db mice. The mechanism may be related to the down-regulation of FOXO1/Ang-2 pathway, the recruitment of endothelial cells to pericytes, and the promotion of the maturation of wound new blood vessels.
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Objective The expression of Ang-2 and HSP90α in serum of patients with non-small cell lung cancer and their correlation with TNM staging were analyzed.Methods From January 2015 to June 2016,40 patients with elderly non-small cell lung cancer and 40 healthy persons were selected as the study subjects.The serum levels of Ang-2 and HSP90 alpha in the subjects were examined and their correlation with the TNM stage of the patients was analyzed.Results Observation of Ang-2 and HSP90α levels in the serum of the patients group were significantly higher than the control group,and the difference was statistical significance(P<0.05);Serum Ang-2 and HSP90α levels TNM Ⅰ-Ⅱ patients were significantly lower than that of stage Ⅲ and Ⅳ,the difference was statistical significance(P<0.05);Serum Ang-2 and HSP90α levels in TNM Ⅲ patients was significantly lower than those in stage Ⅲ and Ⅳ,the difference was statistical significance(P<0.05);TNM staging was positively correlated with the levels of HSP90α in serum,and statistical significance(r=0.425,P<0.05),TNM stage had a remarkably positive correlation with the level of Ang in serum(r=0.525,P<0.05).Conclusion The levels of Ang-2 and HSP90α were significantly higher in the serum of elderly patients with non-small cell lung cancer,and the expression level was positively correlated with TNM stage.
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Objective To investigate the effect of dexamethasone on expressions of angiopoietin-1,2 (Ang-1,2) in rats with acute lung injury induced by phosgene.Methods A total of 36 SD rats were randomly (random number) divided into 3 groups:normal control group that consisted of the rats with air exposure,phosgene group that consisted of the rats with exposure to 8.33 mg/L phosgene (purity 100％,of the same volume as the inhaled air in the normal control group) for 5 minutes and dexamethasone group that consisted of the rats with caudal vein injection of 2.5 mg/kg dexamethasone an hour before exposure to the same dose of phosgene.Wet and dry ratio of the lung (W/D) was calculated,and leukocyte count and total protein content of bronchoalveolar lavage fluid (BALF) were recorded 2 hours later.The concentrations of Ang-1,2 in the serum and BALF were measured by enzyme-linked immunosorbent assay (ELISA).Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the mRNA levels of Ang-1,2 and Tie-2 in the lung tissue.The protein expression of Ang-1,2 and Tie-2 in the lung tissue were quantified by Western blot.Results Compared with phosgene group,the lung W/D,protein content of BALF and WBC count in dexamethasone group were significantly decreased (P ＜ 0.01).Compared with normal control group,Ang-1 and Tie-2 expressions in phosgene group were significantly decreased (P ＜ 0.01).Compared with phosgene group,the serum,BALF and lung tissue of Ang-1 and Tie-2 expressions in dexamethasone group was significantly increased (P ＜0.01).Compared with normal control group,the serum,BALF and lung tissue of Ang-2 expressions in phosgene group were significantly increased (P ＜ 0.01).Compared with phosgene group,the serum,BALF and lung tissue of Ang-2 expressions in dexamethasone group were significantly decreased (P ＜ 0.05,P ＜ 0.01).Conclusion Dexamethasone has a beneficial effect on acute lung injury induced by phosgene in rats by inhibition of Ang-2 and increase in Ang-1 and Tie-2 expressions.
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Angiopoietin(Ang)is a secreted endothelial cell specific growth factor.Ang 2 levels in the body increase in bloodstream during infection.Studies have demonstrated that Ang 2 is a potential therapeutic target in sepsis.This paper reviews the biological function of Ang 2-Tie2 and Ang 2 inhibitors for a potential role of sepsis treatment.
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Objective To explore the expression of Ang -2 and CD105 in breast cancer and their po-tential associations with the cancerization and progression of breast cancer .Methods Thirty patients with breast cancer ( cancerous tissue ) ,15 intraductal papilloma cases ( precancer tissue ) and 15 normal breast tissue were col-lected for each group ,respectively .Immunohistochemistry ,western blot and RT-PCR techniques were used to ex-amine the expressions of Ang -2 and CD105 in cancerous breast tissue ,precancer breast tissue and normal breast tissue at both protein and mRNA levels .The possible correlations of Ang -2 and CD105 expression with clinico-pathological characteristics of the breast cancer were analyzed .Results The expressions of CD105 and Ang-2 in cancer and precancer tissues were higher than in normal tissues at both protein and mRNA levels ,and the trend of their expressions was increased from normal to precancer ,and cancer tissue .The expressions of CD 105 and Ang-2 protein and mRNA were positively correlated with tumor size ,invasion,lymph node metastasis,and negatively correlated with the differentiation of the cancer .Conclusion CD105 and Ang-2 are involved in the canceriza-tion and pregression of breast cancer .These two biomarkers can serve as two useful indicators in assisting diagno-sis and prognosis of breast cancer .
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Objective: To compare the protective effect of Tea polyphenol with that of esmolol on vascular endothelial cells secreting endothelin induced by hypoxia combined Ang-2. Methods: Vascular endothelial cells were divided into 4 groups that included control group,hypoxia+Ang-2 group,hypoxia+Ang-2+tea polyphenol group,hypoxia+Ang-2+esmolol group,and each group comprised eight samples. The changes of endothelin expression level were measured with radioimmunoassay at the time of 0.5 h,6 h,and 24 h. Results: ①The level of endothelin expression in hypoxia+Ang-2 group was higher significantly than that in the control group(P0.05),but there was significantly different at the time of 6 h and 24 h after hypoxia combined Ang-2(P
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Atherosclerosis is a systemic and multifactorial disease, its incidence is raised recently. Cerebral and coronary atherosclerosis have some similar pathogenesis, but their relationship and mechanisms are still remain unclear. Intimal neovascularization in the atherosclerotic plaque was focused with respect to its pathological roles, intimal thickening and atherosclerotic progression. Ang-2, which is an angiogenesis regulating factor, provides a destabilizing signal for endothelial cells, leading to vessel regression or sprouting. However the role and distribution of Ang-2 in atherosclerotic coronary and cerebral arteries are still not well known. Thus, we analyzed 1) atherosclerotic lesion progression 2) relationship of atherosclerosis to Ang-2 expression in human middle cerebral and coronary artery. Paraffin sections from 25 human coronary (COA) and 36 middle cerebral arteries (MCA) were characterized according to AHA classification. In the same person, the score of atherosclerosis progression in COA was higher than that of MCA. In the two kinds of arteries having same atherosclerotic progression, the degree of intimal proliferation and luminal stenosis in COA was higher than that of MCA. Expression of Ang-2 was not shown in normal artery but localized in lumen-lining endothelium, macrophage in preatheroma, atheroma and complicated lesion. Ang-2 expression and infiltration of macrophages were rich in COA than MCA. Our result indicated that cerebral atherosclerosis has some different pathogenic mechanisms with coronary atherosclerosis according to difference of progression and angiogenic factor Ang-2 expression. Thus this is a fundamental study for understanding the progression of atherosclerosis in different vascular beds.
Subject(s)
Humans , Angiogenesis Inducing Agents , Angiopoietin-2 , Arteries , Atherosclerosis , Cerebral Arteries , Classification , Constriction, Pathologic , Coronary Artery Disease , Coronary Vessels , Endothelial Cells , Endothelium , Incidence , Intracranial Arteriosclerosis , Macrophages , Middle Cerebral Artery , Paraffin , Phenobarbital , Plaque, AtheroscleroticABSTRACT
Objective:To study the role of angiopoietin-2(Ang-2) in angiogenesis in oral squamous cell cacinoma(OSCC). Methods:Expression of angiopoietin-2 and CD_34 in 41 cases of OSCC(13 cases with lymph node metastasis)and 10 cases of normal oral mucosa was detected by immunohistochemical SABC method. Microvessel density(MVD) in the samples was counted under microscope. Results:Ang-2 was detected in 28 out of 41(68.29%) cases of OSCC and 2 out of 10(20%) of normal oral mucosa(P