Endothelial Growth Factor Serum Research Articles

The effect of leizumab on serum vascular endothelial growth factor, IL-6, MCP-1 inflammatory factors in neovascular glaucoma.

This study aimed to assess Leizumab's effect on serum endothelial growth factor, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and inflammatory factors in neovascular glaucoma patients. 80 eligible patients treated between January 2021 and April 2023 were enrolled, randomly divided into control and study groups. The control group underwent vitrectomy while the study group received preoperative intravitreal rituximab injection. Measurements included serum and aqueous humor VEGF/PEDF, IL-6/MCP-1 levels, postoperative rebleeding/retinal detachment, and visual acuity changes over 6 weeks. After surgery, patients showed reduced serum VEGF/PEDF levels (P < 0.05), with decreased VEGF and increased PEDF in aqueous humor (P < 0.05). The study group had lower VEGF and higher PEDF levels than the control (P < 0.05). Serum IL-6/MCP-1 levels reduced post-surgery, with the study group lower than control (P < 0.05). Intraocular rebleeding was lower in the study group (P < 0.05), while retinal detachment rates were similar (P > 0.05). Visual acuity differed significantly from week 1 to 6 post-surgery (P < 0.05), with higher acuity in the study group during weeks 1-4 (P < 0.05). Weeks 5-6 follow-up showed no significant difference (P > 0.05). Pre-vitrectomy ranibizumab injection effectively reduced bleeding, VEGF/PEDF levels, inflammatory factors, and improved visual recovery.

A Retrospective Trial Exploring Erzhu Yiren Decoction in Gastric Ulcer with Spleen Deficiency and Dampness-Heat.

Objective To assess the efficacy of Erzhu Yiren Decoction in treating gastric ulcer of spleen deficiency and dampness-heat and its effect on serum NO, EGF, and PGE2 levels. Methods A retrospective study was conducted among 64 patients with gastric ulcers of spleen deficiency and dampness heat admitted to our hospital from September 2019 to May 2020, and they were divided at a ratio of 1 : 1 into an observation group (rabeprazole sodium enteric-coated capsules plus Erzhu Yiren Decoction) and a control group (rabeprazole sodium enteric-coated capsules) based on different treatment methods. The clinical symptom scores, the effective rate of ulcer healing under gastroscopy, the quality of ulcer healing (QOUH), serum nitric oxide (NO), endothelial growth factor (EGF), and prostaglandin E2 (PGE2) levels were compared between the two groups. Results The clinical symptom scores of the observation group after treatment were significantly lower than those of the control group (P < 0.001). The observation group obtained a remarkably higher efficacy of ulcer healing under gastroscopy than the control group (P = 0.039). The observation group outperformed the control group in terms of the number of patients with excellent and good QOUH (P = 0.003, 0.014), but no statistical difference in the number of patients with poor QOUH between the two groups was found (P > 0.05). Serum NO, EGF, and PGE2 levels of the observation group after treatment were significantly better than those of the control group (P < 0.001). Conclusion Erzhu Yiren Decoction can relieve the clinical symptoms of patients with gastric ulcers of spleen deficiency and dampness heat; improve the serum NO, EGF, and PGE2 levels; optimize the mucosal maturity; and enhance the overall efficacy, which merits clinical promotion.

VASCULAR ENDOTHELIAL GROWTH FACTOR AS A MARKER OF ENDOTHELIAL DYSFUNCTION IN THE PREGNANT WOMEN WITH OBESITY

Today, obesity is one of the most common diseases worldwide and is a risk factor for obstetric and perinatal complications. Therefore, the purpose of the study is to determine the vascular endothelial growth factor in the blood serum of pregnant women with physiological body weight and obesity of varying degrees in the first and third trimesters of gestation. Materials and methods. The subjects were divided into 6 groups. The first group (control) consisted of pregnant women with physiological body weight in the first trimester; the second group included pregnant women with physiological body weight in the third trimester; the third group involved pregnant women with obesity Class I in the first trimester (20 women in each group); the fourth group - pregnant women with obesity of Class I in the third trimester (15 women); the fifth group - pregnant women with obesity of Classes II – III in 1st trimester (20 women); the sixth group – pregnant women with obesity of Classes II – III in the third trimester (15 women). Results and discussion. The article presents the evaluation of angiogenesis in pregnant women with physiological body weight and in pregnant women with concomitant obesity. The analysis of the results obtained has demonstrated the following pattern: the blood serum angiogenic factor decreases as obesity increases over I and III trimesters. Conclusions: 1. The endothelial growth factor of blood vessels in pregnant women with physiological body weight increases as pregnancy progresses. 2. Сoncentration of vascular endothelial growth factor in the serum of pregnant women with concomitant obesity in the 1st and 3rd trimesters of pregnancy naturally decreases with increasing severity of obesity, and its indicators in pregnant women with obesity in the 1st trimester can be used to predict the occurrence of obstetric complications associated with obesity.

Highly sensitive electrochemiluminescence biosensor for VEGF165 detection based on a g-C3N4/PDDA/CdSe nanocomposite.

In this work, an electrochemiluminescence (ECL) biosensor was fabricated for the selective detection of vascular endothelial growth factor (VEGF165). g-C3N4/PDDA/CdSe nanocomposites were used as the ECL substrate. Then, DNA labeled at the 5' end with amino groups (DNA1) was immobilized on the surface of g-C3N4/PDDA/CdSe nanocomposite-modified glassy carbon electrode (GCE) by amido linkage. AuNP-labeled target DNA (Au-DNA2) could hybridize with DNA1 to form a double strand. The ECL of the g-C3N4/PDDA/CdSe nanocomposite was efficiently quenched due to the resonance energy transfer between CdSe QDs and Au NPs. After VEGF165 was recognized and bound by Au-DNA2, the double helix was disrupted, and the energy transfer was broken. In this case, Au-DNA2 was released from the electrode surface, and the ECL intensity recovered to a higher level. Under optimal conditions, this ECL biosensor possesses excellent selectivity, accuracy, and stability for VEGF165 detection in a linear range of 2pgmL-1 to 2ngmL-1 with a detection limit of 0.68pgmL-1. In addition, this assay has been successfully applied to the determination of VEGF165 in serum samples. Graphical abstract Schematic representation of the electrochemiluminescence sensor based on a g-C3N4/PDDA/CdSe nanocomposite, which can be determined in the concentration of vascular endothelial growth factor in serum.

Coca cola and pepsi cola impact burns repair and serum levels of endothelial growth factor and vascular endothelial growth factor receptor in rabbits

Objective: The present study was designed to evaluate comparatively the effects of coca cola and pepsi cola on skin burns repair, serum levels of Endothelial Growth Factor (EGF) and Vascular Endothelial Growth Factor Receptor (VEGFR) in rabbits. Methods: Thirty Japanese white rabbits were randomly assigned into three groups; coca cola-treated group, pepsi cola-treated group and control group (n=10). Each rabbit was cauterized to make the second-degree skin cauterization burn (on d 0). Rabbits in coca cola-treated, pepsi cola-treated and control groups drank 20% coca cola, 20% pepsi cola and tap water, respectively. The tensile strength, blood glucose levels and serum levels EGF and VEGFR were determined. Results: Burn repair periods of coca cola-treated group (22.88 ± 3.23 d) and pepsi cola-treated group (22.49 ± 3.02 d) were longer than that of control group (20.25 ± 3.11 d). Tensile strengths of coca colatreated and pepsi cola-treated rabbits were decreased compared to control rabbits. Blood glucose levels of all rabbits were sharply increased following cauterization burns, and reached the peak value on d 3, the increments in coco cola-treated, pepsi cola-treated and control groups were 36.32%, 37.50% and 29.47%, respectively. Serum EGF and VEGFR levels of coco cola-treated and pepsi cola-treated groups were slightly reduced after d 5 in comparison with control group. Conclusions: Ingestion of cola and pepsi cola could inhibit burn repair and physics strength of the healed tissues, also reduced serum EGF and VEGFR levels. Such, burned patients should limit or cease to drink carbonated beverages.

THE EVALUATION NEUROPSYCHOLOGICAL DEVELOPMENT IN PRETERM INFANTS WITH HYPOXIC BRAIN INJURY

We observed 164 preterm newborns with moderate and severe hypoxic brain injury and 25 healthy newborns, who were included into control group. The clinical, laboratory and diagnostic data were analyzed and determined levels of neurospecific enolase in serum, levels of vascular endothelial factor in serum and levels of brain-derived neurotrophic factor in serum during the neonatal period followed with assessment of mental development by the method of Zhurba in the control time. Revealed that additional predictors of adverse mental outcomes in preterm newborns with severe hypoxic brain injury under one year were the intrauterine growth hypotrophic of III level type, the high level of neurospecific enolase in serum and low level of vascular endothelial growth factor in serum in 1 month after delivery.

Triptolide Downregulates Treg Cells and the Level of IL-10, TGF-β, and VEGF in Melanoma-Bearing Mice

Regulatory T cells play a key role in suppressing tumor immunity. Triptolide, a major active component isolated from the Chinese medicinal herb Tripterygium wilfordii, has been proven to possess multiple antitumor activities. Here, we investigated the effect of triptolide on regulatory T cells and on the level of IL-10, transforming growth factor-β, and vascular endothelial growth factor in tumor-bearing mice. Fifty male C57BL/6 mice were randomly grouped as follows: normal control group, model group with B16-F10 cells implanted, and three treatment groups with cyclophosphamide, triptolide-high dose, triptolide-low dose. The proportion of regulatory T cells in the spleen and axillary lymph nodes was evaluated by flow cytometric analysis. Production of cytokines IL-10, transforming growth factor-β, and vascular endothelial growth factor in serum was measured using enzyme-labeled immunosorbent assay kits. The mRNA levels of Foxp3, IL-10, and transforming growth factor-β in the spleen and vascular endothelial growth factor in tumor tissue were detected by real-time PCR. The results showed that triptolide significantly decreased the proportion of regulatory T cells and lowered the Foxp3 level in the spleen and axillary lymph nodes of tumor-bearing mice. Production of IL-10 and transforming growth factor-β in peripheral blood, and the mRNA level of IL-10 and transforming growth factor-β in the spleen were also decreased. Additionally, triptolide could remarkably inhibit production of vascular endothelial growth factor in tumor-bearing mice. In conclusion, our study demonstrated that triptolide might inhibit tumor growth by inhibiting regulatory T cells and some cytokines such as IL-10 and transforming growth factor-β, as well as production of vascular endothelial growth factor.

The Detection of Vascular Endothelial Growth Factor in Serum of Patients with Hemorrhagic Fever with Renal Syndrome

Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease characterized by endothelial cell dysfunction, which results in plasma exosmosis, hyperpermeability, and sometimes hemorrhages. As one of the vascular permeability cytokines, vascular endothelial growth factor (VEGF) might mediate the hyperpermeability caused by HFRS. In the present study, the levels of serum VEGF were measured by competitive inhibition ELISA. We found variable but persistently elevated levels of VEGF throughout the various stages and types of HFRS disease, which suggested that the levels of VEGF were closely correlated to the progression of HFRS. Moreover, elevated levels of VEGF have correlation with the severity and degree of kidney damage. Therefore, to study the relationship between levels of VEGF and disease severity of patients with HFRS is helpful to clarify the pathogenesis of HFRS.

Evaluation of Endostatin and EGF Serum Levels in Patients with Gastric Cancer

THE AIM OF THE STUDY was to assess angiogenesis markers - endostatin and endothelial growth factor (EGF) as markers of detection of gastric carcinoma. MATERIAL AND METHODS. The study involved 20 patients with colorectal cancer (10 women, 10 men) aged 35 - 75 years, mean age = 55 years ± 11.2 who referred to the 2nd Department of General Surgery, Medical University in Lublin between June 2008 and June 2009. The control group comprised 10 volunteers (6 women, 4 men) who underwent upper gastrointestinal (GI) endoscopy due to the reflux disease and in whom gastric cancer was not diagnosed. RESULTS. The mean endostatin concentration in controls was 5.21 ng/mL ± 1.37. Mean concentrations in patients with gastric cancer were higher than those in controls - 5.91 ng/mL ± 1.5. The difference was not statistically significant (p= 0.714). The EGF concentration in the control group was 28.19 pg/mL ± 12.94. EGF concentrations in patients with gastric cancer were higher compared to the control group - 28.8 pg/mL ± 12.63. The difference was not statistically significant (p= 0.85). The mean concentration of endostatin before the operation was 5.91 ng/mL ± 1.5 and after surgery was 5.33 ng/mL ± 2.01, the difference was not statistically significant. CONCLUSIONS. Blood endostatin and EGF quantitative determinations probably is not useful for detection of gastric carcinoma and effectiveness of treatment.

Relationship between serum IL-18 and VEGF levels in patients with prostate cancer

Objective The aim of our study was to analyze interleukin-18 (IL-18) and vascular endothelial growth factor (VEGF) serum levels in patients with prostate cancer before and after operation and the possible correlation between IL-18 and VEGF serum levels.

Lipoxin A4 and Its Analogue Suppress the Tumor Growth of Transplanted H22 in Mice: The Role of Antiangiogenesis

Tumor angiogenesis plays an essential role in carcinogenesis, cancer progression, and metastasis. Some studies indicate that lipoxins, endogenous anti-inflammatory lipid mediators, might be involved in tumor angiogenesis; however, the governing mechanisms are still unknown. In the present study, we examined the effects of exogenous lipoxin A(4) (LXA(4)) in mouse hepatocarcinoma cell line (H22) and H22-bearing mice model. It was found that in H22 cells, LXA(4) inhibited the production of vascular endothelial growth factor and reduced hypoxia-inducible factor-1 alpha level. In addition, its analogue, BML-111, blocked the expression of vascular endothelial growth factor in serum and tumor sections from H22-bearing mice. H&E staining and immunostaining with antibodies against CD34 revealed that BML-111 suppressed tumor-related angiogenesis in vivo, but LXA(4) could not influence the proliferation of primary cultured human umbilical vein endothelial cells. The tumor growth was also inhibited by BML-111. We also found that BML-111 enhanced the in situ apoptosis while inhibiting macrophage infiltration in tumor tissue. The results provide new evidence that LXA(4) suppresses the growth of transplanted H22 tumor in mice through inhibiting tumor-related angiogenesis.

PO-87 Prognostic value of vascular endothelial growth factor (VEGF) serum level and immunohistochemical expression in non-treated patient with chronic lymphocytic leukemia

PO-87 Prognostic value of vascular endothelial growth factor (VEGF) serum level and immunohistochemical expression in non-treated patient with chronic lymphocytic leukemia

Vascular Endothelial Growth Factor (VEGF) Serum Levels Are Associated With Survival in Early Stages of Lung Cancer Patients

ABSTRACTAim: Evaluate the serum vascular endothelial growth factor (VEGF) levels in the prognosis of lung cancer patients. Methods: Fifty-four serum samples were analyzed for VEGF concentrations (79.3% nonsmall cell lung cancer (NSCLC) and 20.7% small cell lung cancer). Results: Patients with serum VEGF-A levels higher than the mean of the patients studied (434.93 pg/mL) presented a shorter median survival time than those with lower levels (p =.04), as in patients with NSCLC tumors (p =.04) and in those with stages I-II (p <.05), and high serum VEGF-A levels. Conclusion: Elevated VEGF serum levels have a negative prognostic impact on survival in NSCLC and early stages of lung cancer patients.

Expression of vascular endothelial growth factor in serum of umbilical blood from the newborns of women with severe pre-eclampsia

Objective To study the expression and significance of vascular endothelial growth factor（VEGF） in serum of umbilical blood from the newborns of women with severe pre-eclampsia.Methods Radioimmunoassay was used to measure the serum VEGF of umbilical blood from 26 newborns of women with severe pre-eclampsia （severe pre-eclmpsia group） and 30 newborns of normal pregnancy women （control group）. According to birth weightgestational age relation,severe pre-edampsia group included 15 newborns small for gestational age （SGA group） and 11 newborns appropriate for gestational age （AGA group）. Results （1） The VEGF level of umbilical vein blood and umbilical artery blood in severe pre-eclmpsia group was significantly higher than that in control group respectively（ t = 2.16, P 〈 0.05; t = 4.82, P 〈 0.01 ）. （2） In control group and severe pre-eclampsia group, the VEGF level in umbilical artery blood was significantly higher than that in umbilical vein blood （ control group： t = 2.24, P 〈 0.05 ; severe pre-cclampsia group： t = 3.00, P 〈 0.01 ）. （3） In both control group and severe pre-eclampsia group, there was no significant correlation respectively between VEGF levels in umbilical vein blood or umbilical artery blood and newborns＇ gestafional age or birth weight. （4） VEGF level of umbilical artery blood in SGA group was significantly higher than that in AGA group as well as in control group（t = 3.22, P 〈 0.01 ; t = 6.80, P 〈 0.01）. Conclusions The serum VEGF level of umbilical vein blood and umbilical artery blood from the newborns of women with severe preeclampsia was significantly higher than that of normal pregnancy women respectively. The VEGF level of umbilical artery blood can reflect the severity degree of the damage of hypertensive disorder complicating pregnancy to their newborns to some degree. Key words: Vascular Endothelial Growth Factor; Severe Pre-eclampsia; Iscliemia-hypoxia; Umbilical Blood; Newborn

Changes in angiogenesis-related factors in serum following autologous bone marrow cell implantation for severe limb ischemia

Objective: Bone marrow mononuclear cell (BM-MNC) implantation (BMI) for critical severe limb ischemia especially for Buerger's disease shows excellent clinical results but the mechanism of this treatment is still unknown. In this study, we investigated the changes in serum levels of angiogenesis-related factors after BMI treatment. Research design/methods: Twelve patients whose BMI treatments were clinically very effective was selected out of ninteen cases, nine patients had Buerger's disease, two patients had arteriosclerosis obliterans and one had systemic sclerosis. Venous bood from femoral vein or brachial vein of the recipient limbs of these patients. Results: Adrenomedulin (AM), soluble vascular cell adhesion molecule-1 (sVCAM-1), and C-reactive protein (CRP) serum levels 24 h after BMI treatment were significantly increased compared with those before BMI treatment (p < 0.05). Vascular endothelial growth factor (VEGF) serum levels after BMI treatment significantly increased between 1 week and 3 months after BMI treatment (p < 0.05). Nitric oxide (NO) serum levels after BMI treatment increased significantly 2 weeks after BMI treatment (p < 0.05). There was no correlation between the numbers of implanted cells and serum levels of measured angiogenesis-related factors that were significantly increased after BMI treatment. Conclusion: It was concluded that the mechanism underlying BMI treatment consists of early and late phases. The early phase involves the direct action by implanted cells, and the late phase involves indirect paracrine action. In addition, it was considered that BMI treatment is effective when we implant a sufficient level of bone marrow (600 ml) to treat severe limb ischemia.

Interferon-α in Combination With Chemotherapy has Potent Antiangiogenic Properties in an Orthotopic Mouse Model for Pancreatic Adenocarcinoma

There are clinical data showing encouraging results for combining chemoradiotherapy with interferon (IFN)-alpha (CapRI scheme) for the treatment of pancreatic carcinoma. Here, it was tried to evaluate the antiangiogenic effect of IFN-alpha in combination with chemotherapy. Mice were inoculated with syngeneic pancreatic carcinoma cells in the pancreas. After 5 days, the animals were treated with 5-fluorouracil (5-FU)+/-IFN-alpha. Tumor growth, vascular endothelial growth factor (VEGF) serum levels and VEGF-R expression, real-time reverse transcription-polymerase chain reaction of mRNA coding for RGS-5, an angiogenic pericyte marker at sites of physiologic and pathologic angiogenesis and impact of IFN-alpha treatment on vessel density by CD31 stain and intravital microscopy were analyzed. The addition of IFN-alpha to 5-FU-treatment decreased tumor volume, reduced serum level of VEGF, and down-regulated the expression of VEGF-receptor significantly. Furthermore, the combination therapy revealed a decrease in vessel density and a down-regulation of RGS-5, which is a protein involved in angiogenic tumor vasculature. IFN-alpha significantly improves the outcome of 5-FU-therapy in treating pancreatic carcinoma. This is at least partly mediated by IFN-alpha antiangiogenic properties, which acts along with 5-FU on the VEGF system, vessel density, and RGS-5 expression in pericytes.

Vascular endothelial growth factor in serum indicates cardiovascular risk in urology patients

We hypothesized that a high serum concentration of vascular endothelial growth factor (VEGF), a cytokine involved in prostate growth which is also upregulated in chronic ischemia, indicates an increased risk of cardiovascular disease and death in urology patients. The serum VEGF concentration was measured in 219 males (mean age 72 years) who sought medical attention because of lower urinary tract symptoms. Data on cardiovascular events and survival were obtained from the hospital registry of Stockholm County and the Death Registry over a period of up to 10 years (mean 6.2 years). After adjusting for the effects of age and smoking, patients with a serum VEGF level in the upper 20% of the cohort (>500 pg/ml) had an increased risk of developing cardiovascular disease (hazard ratio 2.18; 95% CI 1.04-4.60), including acute myocardial infarction (3.36; 1.35-8.41) and stroke (3.98; 1.61-9.86). They also had an increased risk of death (1.74; 1.01-3.00). These differences from patients with a lower serum VEGF concentration (<300 pg/ml) were manifested 2-5 years after the blood sample was taken. An elevated VEGF level in peripheral blood was a risk factor for subsequent development of cardiovascular disease.

Vascular Endothelial Growth Factor and Nitric Oxide Serum Levels in Arterial Hypertension

Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells and an inducer of the angiogenic procedure. Endothelial nitric oxide (NO) is a potent vasodilator. Because both are implicated in vascular function, it is possible that they would be significantly affected in arterial hypertension. The aim of the study was the investigation of the levels of the two substances in blood serum and their potential relation in patients with untreated essential arterial hypertension compared to healthy individuals. VEGF levels were found 129.1 ± 135.9 pg/mL in a group of 28 untreated hypertensive patients vs. 209.0 ± 133.3 pg/mL in a group of 28 healthy individuals (p = 0.008). Nitrites and nitrates levels (as an indirect index of calculating NO levels) were also lower in hypertensive patients than in healthy individuals (19.8 ± 9.7 μmol/L vs. 29.6 ± 15.9 μmol/L, p = 0.014). A positive correlation between NOx (nitrites and nitrates levels) and VEGF was found in healthy individuals (r = 0.55, p = 0.003), but there was no correlation in hypertensive patients. The significant decrease of serum VEGF and NO in arterial hypertension and the existence of a correlation between the two substances in healthy subjects that did not exist in the hypertensive patients are findings that need evaluation.

Elevated levels of vascular endothelial growth factor in serum of patients with D+ HUS.

The pathogenesis of hemolytic uremic syndrome (D+ HUS) is characterized by endothelial damage of glomeruli and tubules within the kidney. In several other diseases in which glomerular endothelial damage occurs, elevated serum levels of vascular endothelial growth factor (VEGF) have been reported. VEGF is involved in angiogenesis, permeabilization of blood vessel endothelium, and wound repair. In this study we evaluated VEGF levels in the serum of 40 D+ HUS patients in the acute phase and during the course of the disease. VEGF levels were measured using a double-sandwich ELISA. Indirect immunohistochemistry was performed for the detection of VEGF in renal biopsy material of 3 HUS patients. Significantly elevated VEGF levels were found in HUS patients compared with controls in both serum ( P<0.001) and plasma ( P<0.05). A significant relationship was found between VEGF levels and severity of the disease according to the classification of Gianantonio ( P<0.05). Levels of VEGF in blood increased during the 2nd and 3rd week after HUS was diagnosed. Immunohistochemistry of renal biopsy material showed increased levels of the receptors for VEGF in the glomeruli. During the course of HUS, plasma VEGF levels increase and the increase is dependent on the severity of the disease. This is probably associated with the repair process.

Angiogenic and antiangiogenic balance regulates concomitant antitumoral resistance.

Concomitant antitumoral resistance (CAR), the phenomenon by which the growth of distant secondary tumor implants or metastases in some tumor-bearing hosts is inhibited by the presence of a primary tumor, has been previously ascribed to an antiangiogenic process. Here, we investigated vascular endothelial growth factor (VEGF) and endostatin serum levels in nude or BALB/c mice bearing human lung tumors (Calu-6 and H460) or murine mammary tumors (M3MC, M-234p and M-234m), respectively. In these experimental models we previously found an association between in vivo generation of CAR and in vitro conversion of plasminogen into angiostatin. Serum endostatin level in CAR+ Calu-6-bearing mice was significantly higher than in CAR- H460 counterpart. Sera from mammary tumor-bearing mice showed similar levels of endostatin, regardless of their ability to induce CAR. Conversely, serum VEGF levels in mice bearing CAR+ tumors were lower than those found in CAR- tumor-bearing hosts. Immunostaining with an anti-CD31 antibody revealed that secondary tumors subjected to CAR were significantly less vascularized than primary tumors, while this difference was not observed in CAR- tumors. In vitro studies showed an inhibitory effect of sera from CAR-inducing tumors on endothelial cell proliferation as compared to normal sera, whereas sera from non-CAR-inducing tumors did not alter endothelial proliferation and, in some instances, even caused stimulation of endothelial proliferation. These data suggest that the antiangiogenic mechanism operating in concomitant antitumoral resistance is the result of an increase in the ratio of antiangiogenic/proangiogenic regulators. The levels of the factors involved in this phenomenon can vary in the different tumor models, but the trend favoring the inhibition of angiogenesis is always conserved.