Expression Levels Of Ang-2 Research Articles

Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous.

Henoch-Schönlein purpura (HSP) and pediatric-onset systemic lupus erythematosus (pSLE) are closely associated with vasculitis and vascular diseases. This study aimed to investigate the clinical diagnostic values of Ang-1, Ang-2, and Tie2 for HSP and pSLE. We surveyed 82 HSP patients, 34 pSLE patients, and 10 healthy children. The expression levels of Ang-1, Ang-2, and Tie2 in the serum and urine were assessed using enzyme-linked immunosorbent assay. The diagnostic values of Ang-1, Ang-2, and Tie2 for HSP and pSLE were evaluated using receiver operating characteristic curve analysis. The results revealed that the serum and urine expression levels of Ang-2 and Tie2 were significantly elevated in HSP and pSLE patients, whereas the Ang-1/Ang-2 values were reduced. Additionally, Ang-1 was highly expressed in the serum and urine of HSP patients and in the serum of pSLE patients. Ang-1, Ang-2, and Tie2 showed differential expression in various types of HSP and pSLE compared with their expression in healthy controls. In summary, Ang-1, Ang-2, and Tie2 can serve as biomarkers for HSP and pSLE. Moreover, Ang-1/Ang-2 values are reduced in HSP and pSLE patients. Ang-1, Ang-2, and Tie2 can be used as biomarkers for HSP and pSLE.

Angiopoietin-2 expression and its relationship with lymphangiogenesis and clinicopathological characteristics in cutaneous malignant melanoma.

The aim of this study was to investigate angiopoietin-2 (Ang-2/ANGPT2) expression and its relationship with lymphangiogenesis and clinicopathological characteristics in cutaneous malignant melanoma (CMM). Gene expression differences between metastatic melanoma and melanoma in situ in 472 patients from the TCGA database were analyzed. The target gene Ang-2 was screened. A clinical study was conducted to analyze the correlation between Ang-2 expression in CMM and tumor-associated lymphangiogenesis. A total of 42 patients with primary CMM who underwent extended tumor resection procedures at the Affiliated Hospital of Jiangsu University were included in this study. Clinical data (gender, age, lymph node metastasis, Breslow thickness, and clinical stage) were collected. The expression levels of both Ang-2 and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) proteins were detected by immunohistochemistry (IHC). Lymphatic vascular density (LVD) was counted by using LYVE-1 to label lymphatic endothelial cells (LECs) in peritumoral and intratumoral areas per high-magnification field of view. Statistical analysis was performed using the Pearson correlation test and Student's t-test. Using the TCGA database, it was found that the gene expression level of Ang-2 in 368 cases of metastatic melanoma was significantly higher than that in 104 cases of melanoma in situ. Correlation analysis showed a significant relationship between Ang-2 and LYVE-1, and vascular endothelial growth factor receptor 3(VEGFR3) expression, respectively, in CMM. Moreover, the optimal cutoff value of survival analysis showed that high Ang-2 expression in CMM had a worse prognosis, based on data from the TCGA database. Our research showed that Ang-2 was more highly expressed in the group of patients with lymph node metastasis and in the group of stage 3C-4 patients than in the group of patients with no lymph node metastasis and in the group of stage 0-3B patients. Our research also showed that LVD in the group of patients with lymph node metastasis and in the group of stage 3C-4 patients was significantly higher than that in the group of no lymph node metastasis and in the group of stage 0-3B patients, respectively. Breslow thickness also correlated with Ang-2 expression and LVD. Ang-2 expression was not related to sex or age. Ang-2 expression was obviously correlated with LVD. An evaluation of Ang-2 expression and LVD can be used to predict the risk of tumor lymphatic metastasis and determine the prognosis of CMM. These results may also provide a new clinical treatment strategy for CMM.

A Correlative Study Between IVIM-DWI Parameters and the Expression Levels of Ang-2 and TKT in Hepatocellular Carcinoma.

BackgroundNoninvasive evaluation of the expression of angiopoietin-2 (Ang-2) and transketolase (TKT) in hepatocellular carcinoma (HCC) is of great significance for the clinical development of individualized treatment plans. However, the correlation between intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and the expression of Ang-2 and TKT has not been reported. We sought to investigate the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs.MethodsConventional non-enhanced magnetic resonance imaging (MRI) and IVIM-DWI and dynamic contrast MRI were performed for 61 patients with HCC before surgical treatment. Various IVIM-DWI parameters, such as apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*) and fraction of fast apparent diffusion coefficient (f), were calculated using Function-MADC software. Expression levels of Ang-2 and TKT in HCC were detected via immunohistochemical staining and classified into two grades. Independent sample t tests were used to compare differences in parameters between the two groups. The Spearman rank correlation test was used to analyze the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs.ResultsThe D* and f values were significantly higher in the high Ang-2 group than in the low Ang-2 group; there were no obvious between-group differences in ADC and D. Ang-2 expression was positively correlated with D* and f but not with ADC and D. The ADC and D values were significantly lower in the high TKT group than in the low TKT group, whereas the between-group differences for D* and f were not significant. TKT expression was negatively correlated with ADC and D but not with D* and f.ConclusionsIVIM-DWI can be used to evaluate Ang-2 and TKT expression in HCC.

MiR-155 expressed in bone marrow-derived lymphocytes promoted lipopolysaccharide-induced acute lung injury through Ang-2-Tie-2 pathway

Acute lung injury (ALI) is a type of diffuse lung inflammation with a high mortality rate. Studies show that miR-155 plays an important role in inflammation. Here, we investigated the role of miR-155 in lipopolysaccharide (LPS)-induced ALI. The mice with bone marrow transplantation between MiR-155 knockout and wild-type were used as animal models of LPS-induced sepsis. In response to LPS injection, ALI was less severe in miR-155 knockout mice than in wild-type mice, and mainly manifested as reduced pulmonary vascular leakage, pulmonary edema, and neutrophil infiltration. The expression levels of Ang-2 and apoptosis-associated caspases-3 and -9, as well as myosin light chain (MLC) phosphorylation in the lungs were also decreased. A bone marrow transplantation experiment showed that miR-155 expressed in bone marrow-derived lymphocytes rather than lung parenchymal lymphocytes promoted inflammation. Findings suggest that miR-155 expressed in bone marrow-derived lymphocytes promoted LPS-induced ALI through the modulation of the Ang-2-Tie-2 pathway.

The clinical and prognostic significance of FIS1, SPI1, PDCD7 and Ang2 expression levels in acute myeloid leukemia

ObjectivesThe marked heterogeneity of acute myeloid leukemia (AML) renders precisely predicting patient prognosis extremely difficult. Genetic alterations, fusions and mutations, may result in misexpression of key genes in AML. We aimed to investigate the expression patterns of 4 novel genes; FIS1, SPI1, PDCD7 and Ang2 to determine their potential prognostic role in AML patients. MethodsBone marrow mononuclear cells were analyzed for of FIS1, SPI1, PDCD7 and Ang2 expression levels by real-time quantitative PCR as well as of FLT3/ITD and NPM1 mutations in 100 newly diagnosed cytogenetically normal (CN-AML) patients, and 100 non-malignant controls. ResultsFIS1, SPI1, PDCD7 and Ang2 were significantly overexpressed in CN-AML patients (p < 0.001). Their high expression levels were significantly associated with lower complete remission (CR) rate, shorter relapse-free survival (RFS) and overall survival (OS). On multivariate analysis, high FIS1 expression showed a significant impact on CR response after induction therapy (OR = 88.777, 95% C.I: 2.85–2765.78, p = 0.011) while high PDCD7 appeared to be an independent risk factor for RFS (HR = 5.107, 95% C.I: 1.731–15.066, p = 0.003) and OS (HR = 7.353, 95% C.I: 1.859–29.079, p = 0.004) in CN-AML patients. ConclusionsFIS1 and PDCD7 expression are considered independent risk factors and should be integrated into the current AML stratification system.

Differential roles of p38 MAPK and ERK1/2 in angiopoietin-2-mediated rat pulmonary microvascular endothelial cell apoptosis induced by lipopolysaccharide.

Angiopoietin-2 (Ang-2) is a Tie-2 ligand that destabilizes vascular structures, enhances vascular permeability and induces vascular regression and endothelial cell apoptosis. Although there is evidence for the involvement of the Ang/Tie2 axis in acute lung injury (ALI), the underlying mechanisms involved in Ang-2-induced cell apoptosis are not well understood. In this study, whether Ang-2 contributes to microvascular endothelial cell injury and mediates lipopolysaccharide (LPS)-induced endothelial cell apoptosis and its associated signaling pathways was investigated. Exposure of rat pulmonary microvascular endothelial cells (RPMVECs) to LPS, Ang-2 and related inhibitors was performed to measure the expression levels of Ang-2, the activation of mitogen-activated protein kinases (MAPKs), the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, and expression of the apoptosis-related proteins Bax and Bcl-2 using western blotting, reverse transcription-quantitative polymerase chain reaction, flow cytometry and fluorescence microscopy. The expression of Ang-2 in the RPMVECs was increased by LPS independent of time. The phosphorylation of p38 MAPK and ERK1/2 was significantly upregulated and the activation of apoptosis-related proteins Bax and Bcl was mediated by Ang-2. In addition, inhibition of the p38 pathway by SB203580 attenuated the Ang-2-mediated cell apoptosis, but inhibition of the ERK1/2 pathway by PD98059 exerted an anti-apoptotic effect against Ang-2. In conclusion, LPS-induced apoptosis is partly mediated via stimulation of p38 and ERK1/2 signaling pathways, where Ang-2 acts an inflammation-related factor to participate in the course of cell apoptosis in RPMVECs.

Abnormal expression of angiopoietin-2 associated with invasion, metastasis and prognosis of lung cancer

Objective: To investigate the relationship between abnormal angiopoietin-2 (Ang-2) expression and invasion/metastasis of lung cancer. Methods: Totally 122 cases of postoperative primary lung cancer tissues and their paracancerous tissues from Jan. 2009 to Dec. 2010 were collected from Affiliated Hospital of Nantong University and Ang-2 expression was analyzed by immunohistochemistry. At the cellular level, the protein and mRNA levels of Ang-2 in lung epithelial cell line Beas-2B and four lung cancer cell lines (SPCA-1, NCI-1650, A549 and NCI-H1975) were observed. The most effective Ang-2-shRNA for Ang-2 transcription was screened and transfected into A 549 lung cancer cells. The Ang-2 expression, Ang-2 gene transcription, cell proliferation, invasion/metastasis, and epithelial-mesenchymal transition (EMT) abilities of lung cancer cells were analyzed by Western blotting, fluorescent quantitative reverse transcriptase PCR, Cell Counting Kit-8 assay, and Transwell cell models for exploring the relationship between Ang-2 expression and invasion/metastasis of lung cancer. Results: The higher Ang-2 expression levels in lung cancerous tissues were closely related to tumor diameter (P=0.008), differentiating degree (P=0.033), TNM stage (P=0.025) and 5-year survival rate (P<0.001). According to the Kaplan-Meier survival curves, the 5-year survival rate of patients with higher expression levels of Ang-2 (16.1%) was significantly poorer than that of patients with lower Ang-2 (80.0%, P<0.001). Significant difference of 5-year survival rate was found in patients with different Ang-2 levels at TNM stage Ⅰ(P<0.001), but not at stage Ⅱ, Ⅲ and Ⅳ. Among Beas-2B and four lung cancer cell lines, the protein and mRNA levels of Ang-2 in A549 cells were the highest. After Ang-2-shRNA-1 plasmid successfully transfected into A549 cells, cell proliferation rate was significantly lower than that in the shRNA-negative or blank group at a time-dependent manner. The significant decrease of the invasion, migration and EMT abilities were also found in A549 cells after transfection of Ang-2 shRNA. Conclusion: Abnormal expression of Ang-2 is closely related to invasion, migration and prognosis of lung cancer, and interfering the activation of Ang-2 would be a novel molecular-targeted therapy for lung cancer.

Curative effect of stereotactic radiotherapy combined with TACE for patients with hepatic metastases of colorectal cancer and influence on the expressions of omentin-1 and Ang-2

Objective To explore the curative effect of stereotactic radiotherapy combined with transcatheter arterial chemoembolization (TACE) for patients with hepatic metastases of colorectal cancer and influence on the expressions of omentin-1 and angiopoietin-2 (Ang-2). Methods A total of 90 patients with hepatic metastases of colorectal cancer from December 2013 to December 2015 in our hospital were selected as the research objects. Patients were divided into observation group and control group according to random number table method with 45 cases respectively. Patients in control group were treated with TACE, and patients in observation group were treated with stereotactic radiotherapy combined with TACE. After treatment, the clinical efficacy, expression levels of plasma omentin-1 and Ang-2, score of quality of life and adverse reaction were compared in the two groups. Results The objective response rate in observation group (82.2%) was significantly higher than that in control group (60.0%), and the difference was statistically significant (χ2=5.409, P=0.020). After treatment, the omentin-1 and Ang-2 expression levels in observation group were lower than those in control group [(43.7±18.1) ng/ml vs. (52.1±17.9) ng/ml, t=2.214, P=0.029; (2.0±0.2) g/L vs. (2.3±0.3) g/L, t=6.028, P<0.001]. The score of quality of life in observation group was significantly higher than that in control group [(87.6±11.2) vs. (68.7±10.3)], and the diffe-rence was statistically significant (t=8.332, P<0.001). There were no differences on the adverse reaction rates such as abnormal liver function (35.6% vs. 42.2%, χ2=0.421, P=0.517), nausea and vomiting (44.4% vs. 37.8%, χ2=0.413, P=0.520), skin injury (6.7% vs. 0, χ2=3.101, P=0.078) and fever (35.6% vs. 31.1%, χ2=0.202, P=0.655) between the two groups. Conclusion The implementation of stereotactic radiotherapy combined with TACE in the treatment of hepatic metastases of colorectal cancer is a safety and effective method. It can significantly reduce the expression levels of plasma omentin-1 and Ang-2, inhibit of tumor angiogenesis, and improve the quality of life of patients. Key words: Colorectal neoplasms; Radiosurgery; Transcatheter arterial chemoembolization; Angiopoietin-2; Omentin-1

Effect of Hua Yu Xiao Zheng decoction on the expression levels of vascular endothelial growth factor and angiopoietin-2 in rats with endometriosis.

The aims of the present study were to investigate the effects of a traditional Chinese medicine, Hua Yu Xiao Zheng (HYXZ) decoction, on surgically induced endometriosis in a rat model and to determine the possible underlying regulatory mechanisms. A total of 108 female Sprague-Dawley rats were divided into the control group (n=12) and endometriosis group (EM group; n=96), in which endometriosis was surgically induced in model rats by autotransplantation of endometrial tissues and 72 rats survived. After 3 weeks, the EM model rats were randomly divided into four subgroups (n=18), including the untreated model group, and three groups administered 7, 14 or 21 g/kg HYXZ decoction. Following 28 days of treatment, the associated proteins and genes of ectopic endometrial tissues were analyzed using immunohistochemistry, western blotting and quantitative polymerase chain reaction to investigate the underlying mechanisms. Compared with the model group, the size of the endometriotic implants decreased significantly in the HYXZ-treated groups. Furthermore, the expression levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) were significantly decreased in HYXZ-treated groups compared with the model group. These results indicate that HYXZ affected the inhibition of angiogenesis and decreased the endometriotic implant volumes and histopathological scores. The effectiveness of HYXZ may be partially attributed to the decrease of VEGF and Ang-2 expression levels in the ectopic endometrium.

Oncogenic function of angiopoietin-2 in vitro and its modulation of tumor progression in colorectal carcinoma.

Angiopoietin-2 (Ang-2) has been investigated in cancer primarily in terms of its angiogenic function, and its role as an oncogene has yet to be elucidated. The current study hypothesized that Ang-2 may be an oncogene and have a function in tumor progression. An investigation of the function of Ang-2 in the LoVo colorectal cancer (CRC) cell line in vitro, which expresses a high level of Ang-2, was performed by knocking down endogenous expression with a targeted short hairpin RNA. The aggressive phenotypic effects of Ang-2 on experimental and control group cells were assessed using cell proliferation, migration and invasion assays. The association between Ang-2 expression levels and clinicopathological factors was evaluated in 415 CRC tissues using immunohistochemistry. Suppressing Ang-2 expression decreased cellular proliferation, invasion and migration in an in vitro study. Ang-2 overexpression was observed in 46% of patients with CRC and was significantly associated with pT (P=0.048), pN (P<0.001), venous invasion (P=0.023), lymphatic invasion (P<0.001) and tumor-node-metastasis stage (P=0.022). Furthermore, Ang-2 overexpression was an independent prognostic factor in pN stages 1 and 2. These results reveal that Ang-2 may be an oncogene in colorectal carcinogenesis and its expression may exert aggressive phenotypic effects during tumor progression. In addition, Ang-2 expression may serve as a prognostic marker and a potential drug target.

Hypoxia inducible factor-2 alpha regulating hypoxia-induced angiogenesis via angiopoietin-2 pathway

Objective To investigate the mechanisms of hypoxia inducible factor-2 alpha (HIF-2a) regulating human umbilical vein endothelial cells (HUVECs) under hypoxic conditions. Methods The experimental study was adopted. (1) HUVECs in logarithmic growth phase were taken: HUVECs without any disposals as control group, HUVECs with shRNA transfection control as shRNA control group, HUVECs with HIF-2α shRNA transfection as HIF-2α shRNA group and HUVECs with HIF-2α shRNA transfection then added rh-Ang-2 as HIF-2α + rh-Ang-2 group. (2) Western blot testing: the expressions of Ang-2 and HIF-2α proteins in HUVECs were cultured under hypoxia conditions at 0, 2, 4, 8, 12, 16, 20 hours, and the levels of which were detected in the control group, shRNA control group and HIF-2α shRNA group. (3) Enzyme-linked immunosorbent assay(ELISA): the level of Ang-2 protein in supernatant of HUVECs was detected in the control group, shRNA control group and HIF-2α shRNA group. (4)The amounts of endothelial cell tubes in HUVECs among the 4 groups were detected by tube formation experimental testing.(5)Transwell method was performed to detect the amounts of cells migration in HUVECs and hepatoma cells SMMC-7721 migration intervened by supernatant of HUVECs among the 4 groups. Measurement data with normal distribution were presented as ±s, repeated measurement data were analyzed by the repeated measures ANOVA, comparison among groups and pairwise comparison were conducted respectively by the one-way ANOVA and Dunnett's test. Results (1)Western blot test: the expression levels of Ang-2 and HIF-2α proteins in HUVECs under hypoxia conditions at 0, 2, 4, 8, 12, 16, 20 hours were 0.110±0.011, 0.120±0.020, 0.210±0.070, 0.410±0.100, 0.520±0.090, 0.790±0.130 1.010±0.220 and 0.180±0.090, 0.410±0.070, 0.470±0.110, 0.470±0.070, 0.580±0.120, 0.690±0.140, 0.920±0.130, respectively, and which were increased after culturing under hypoxia conditions and had an ascending tendency as the hypoxia time extended, with statistically significant differences (F=403.550, 3 265.587, P<0.05). The expression levels of Ang-2 and HIF-2α proteins in the control group, shRNA control group and HIF-2α shRNA group were 1.030±0.180, 1.070±0.120, 0.210±0.070, and 0.940±0.110, 0.930±0.190, 0.170±0.021, respectively, showing statistically significant differences (F=290.242, 26.688, P<0.05). (2) The results of ELISA: the expression levels of Ang-2 in the control group, shRNA control group and HIF-2α shRNA group were (433.2±9.7)ng/L, (438.3±2.6)ng/L, (114.6±4.2)ng/L, with a statistically significant difference(F=2 642.180, P<0.05). (3) The results of tube formation experiments: the number of endothelial cell tubes in the control group, shRNA control group, HIF-2α shRNA group and HIF-2α + rh-Ang-2 group were 48.3±2.5, 47.4±3.1, 19.7±1.5 and 38.3±2.1, respectively, with a statistically significant difference (F=148.196, P<0.05). (4) The results of Transwell method: ① the number of HUVECs migration in the control group, shRNA control group, HIF-2α shRNA group and HIF-2α + rh-Ang-2 group were 140.3±3.5, 142.7±2.1, 42.7±3.1 and 78.1±4.2, respectively, showing a statistically significant differences (F=212.205, P<0.05). ②The results of Transwell method: the number of SMMC-7721 cells migration after intervening using four different supernatant in the control group, shRNA control group, HIF-2α shRNA group and HIF-2α + rh-Ang-2 group were 106.7±5.5, 102.7±6.6, 63.0±3.3 and 96.7±2.1, respectively, showing a statistically significant difference (F=55.122, P<0.05). Conclusion HIF-2a could not only affect HUVECs formation but also promote SMMC-7721 cells migration via regulating Ang-2 expression. Key words: Liver neoplasms; Hypoxia inducible factor-2α; Angiopoietin-2; Angiogenesis; Migration

Synergistic effect of vascular endothelial growth factor and angiopoietin-2 on progression free survival in multiple myeloma

Bone marrow neoangiogenesis plays an important role in multiple myeloma (MM) and depends on the interplay of angiogenic cytokines. We investigated the levels of angiogenic cytokines such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin (Ang)-1, Ang-2 and hypoxia inducible factor-1 alpha (HiF-1α) in MM patients and their association with treatment outcome. Serum levels and mRNA expression of VEGF, Ang-2, Ang-1, bFGF and HiF-1α were evaluated in 71 MM patients using enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. In multivariate Cox regression analysis, serum levels of VEGF≥756pg/ml (HR 2.2, 95% CI 1.02–4.91; p=0.045) and relative mRNA expression levels of Ang-2≥0.93 (HR 21.0, 95% CI 6.27–70.45; p<0.001) were predictive of inferior progression free survival (PFS) and patients with concomitant increase in VEGF and Ang-2 had poor outcome compared to the rest of the patients (HR 32.6, 95% CI 7.20–148.36; p<0.001). These results suggest that VEGF and Ang-2 act in synergy and their expression levels at presentation are predictive of PFS in MM.

Interfering growth of malignant melanoma with Ang2-siRNA

To investigate the intervention therapy effect on the growth of malignant melanoma, we have made an observation of expression levels of Ang2 in malignant melanoma cells, which was transduced by small interfering RNA (Ang2-siRNA) of Ang2 in vitro and in vivo. We successfully constructed Ang2-siRNA lent virus, and constructed nude mice model by transplanting malignant melanoma. Ang2-siRNA lent virus inhibited Ang2 mRNA of malignant melanoma in vitro and in vivo, and inhibited malignant melanoma tumor growth at the same time. Ang2-siRNA lent virus can interfere expression levels of Ang2 in malignant melanoma cells, inhibit tumor growth, and silent Ang2 gene expression, which may pave a new way for clinical gene therapy of malignant melanoma.

Differential expression of VEGF‐A and angiopoietins in cartilage tumors and regulation by interleukin‐1β

Vascular endothelial growth factor (VEGF)-A and angiopoietin (Ang)-1 and Ang-2 are key factors in angiogenic signaling. In this study the expression of these factors was identified in cartilage tumors. As interleukin (IL)-1beta has been found to be an indispensable factor in angiogenic signaling, we further analyzed the effect of IL-1beta on the expression of VEGF-A, Ang-1, and Ang-2 using a previously established cell culture model. Surgical specimens of enchondromas, conventional chondrosarcomas, and dedifferentiated chondrosarcomas were obtained from 72 patients. VEGF-A, Ang-1, and Ang-2 mRNA expression was detected by conventional and quantitative reverse transcription polymerase chain reaction (PCR). VEGF-A expression was also detected by immunohistochemistry or Western blot. Differential expression of VEGF-A, Ang-1, and Ang-2 was clearly demonstrated in cartilage tumors. VEGF-A expression was positively correlated with the tumor type. Higher VEGF-A expression levels were detected in conventional chondrosarcomas Grades II and III (using a 3-tier grading system) than in dedifferentiated chondrosarcomas (P < .05). A typical pattern of VEGF-A isoforms was identified, including VEGF(121), VEGF(145), VEGF(165), and VEGF(189). Ang-1 presented as a low-level transcript with slightly elevated levels in chondrosarcomas (P < .05). Highly variable Ang-2 expression levels were detected in solitary cases of conventional chondrosarcomas. IL-1beta regulated VEGF-A and Ang-1 expressions in a dose-dependent manner. Whereas low IL-1beta concentrations increased VEGF-A and Ang-1 transcription, high IL-1beta concentrations had the opposite effect. IL-1beta did not activate Ang-2 expression. Angiogenic signaling in cartilage tumors is variable and at least partly regulable by IL-1beta. The findings are of therapeutic relevance, either as a desired effect or a side effect in medical treatment.

Expression of Angiopoietin-1, Angiopoietin-2, and Tie2 Genes in Normal Ovary with Corpus luteum and in Ovarian Cancer

Objective: The recent discovery of angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) has provided novel and important insights into the molecular mechanisms of blood vessel formation. Ang1 and Ang2 bind with similar affinity to the endothelial cell tyrosine kinase receptor Tie2. Our purpose was to assess the potential role of the Ang/Tie2 system in physiological and pathological angiogenesis in the ovary. Methods:Ang1, Ang2, and Tie2 gene expression in 14 normal ovaries with corpus luteum (CL) and in 19 cases of ovarian cancer were analyzed by polymerase chain reaction of RNA after reverse transcription. The level of each gene expression was presented by the relative yield of each gene to the β₂-microglobulin gene, respectively. Furthermore, cellular distribution of Ang1 and Ang2 mRNA was examined by in situ hybridization, and localization of Tie2 was studied by immunochemistry. Results: The Ang1, Ang2, and Tie2 gene expression in normal ovary with CL ranged from 0.18 to 1.06 (median 0.54), 0.31–2.64 (median 1.01), and 0.10–0.47 (median 0.20), respectively. The expression of these same genes in ovarian cancer ranged from 0.06 to 0.75 (median 0.14), 0.69–1.59 (median 1.12), and 0.04–0.35 (median 0.15), respectively. Ang1 gene expression in normal ovary with CL was significantly higher than that in ovarian cancer (p = 0.0004). The gene expression levels of Ang2 and Tie2 were statistically the same in both groups. There was a significant correlation between Ang1 gene expression and Tie2 gene expression in normal ovary with CL (r = 0.619, p = 0.018). No such significant correlation was found in ovarian cancer. Moreover, Ang2 gene expression showed no significant correlation with the Tie2 gene expression either in normal ovary with CL or in ovarian cancer. Transcripts for Ang1 were observed in CL cells and endothelial cells around CL, and in tumor cells and endothelial cells at the periphery of tumor invasion. Ang2 transcripts were expressed in the same patterns. Tie2 expression was positive primarily in the endothelial cells around CL and in those at the periphery of tumor invasion. Conclusion: Our results indicate that there is a difference in the Ang/Tie2 gene expression between physiological and pathological angiogenesis in the ovary. This finding may aid in the development of new therapeutic interventions for ovarian cancer.