Serum bFGF Research Articles

Serum levels of VEGF and bFGF in infantile hemangiomas treated with propranolol.

Infantile hemangiomas (IH) represent the most common type of benign tumors of infancy. Vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) have a central role in the pathogenesis of infantile hemangiomas. In this prospective study, we aimed to investigate the relationship between serum VEGF and bFGF levels and clinical characteristics and the serological changes in VEGF and bFGF levels associated with propranolol treatment in infants diagnosed with IH. Blood samples were taken from 34 patients with IH and 10 controls. Serum VEGF and bFGF levels were studied by ELISA. At initial diagnosis, median serum bFGF levels were 11.1 ng/ml (4.8-16.6) in patients with IH (n=34) and 2.6 ng/ml (1.7-4.7) in controls (p < 0.001), and, median serum VEGF levels for same groups were 58.5 ng/ml (25.3-190.2) and 11.4 ng/ml (8.2-19.8) (p < 0.001), respectively. Serum VEGF and bFGF levels were not correlated. In 18 infants who were treated with propranolol with serial measurements, median serum bFGF levels were 10.7 ng/ml, 9.8 ng/ml and 10.5 ng/ml (p= 0.8), and median serum VEGF levels were 68.6 ng/ml, 63.5 ng/ml and 45.1 ng/ml (p < 0.001) at initial diagnosis, at first and third months, respectively. Median regression rates of the hemangiomas at the first and third months were -%47.3 and -%58.3 (p < 0.001), respectively. Serum bFGF levels didn`t change in time. Serum VEGF levels seemed to follow the natural course of IH and might be a marker for follow-up. The contribution of propranolol treatment should also be considered.

Traditional versus Percutaneous Transforaminal Endoforaminal Discectomy Effect on the Nervous System Function and Serum LEK, GFAP and PGE-2 in Patients with Senile Lumbar Spinal Stenosis.

To compare the influence of percutaneous transforaminal endoscopic discectomy (PTED) and traditional operation on the nervous system function and the serum leu-enkephalin (LEK), glial fibrillary acidic protein (GFAP) and prostaglandin E-2 (PGE-2) in patients with senile lumbar spinal stenosis. Experimental study. Department of Orthopedics Two, Xinjiang Changji Hui Autonomous Prefecture People's Hospital, Xinjiang, China, from March 2017 to March 2018. A total of 146 patients with senile lumbar spinal stenosis were randomly divided into control group and observation group, 73 in each group. Control group underwent traditional operation, while the observation group underwent PTED. General situation of operation, serum LEK, GFAP, PGE-2, American Spinal Injury Association (ASIA) score and Japanese Orthopaedic Association (JOA) score were compared. Intraoperative blood loss in observation group was less than that in control group (p<0.001). Both operation time and length of hospital stay in observation group were shorter than those in control group (both p<0.001). At 24 hours later after operation, both levels of serum LEK and ASIA score in observation group were higher than those in control group (p=0.006 and p<0.001, respectively), and levels of serum GFAP and PGE-2 and JOA score in observation group were all lower than those in control group (all p<0.001). Compared with traditional operation, PTED has the advantages of less intraoperative blood loss, shorter operation time and length of hospital stay, etc. Besides, PTED can effectively reduce serum LEK, BFGF and PGE-2 expression in patients; and dramatically improve their nervous system function and lumbar function.

Correlation of the Serum bFGF Level with MDS Typing, Serum IL-32 Level and Prognosis

To investigate the correlation of serum bFGF level with MDS typing, serum IL-32 and prognosis. A total of 62 patients with myelodysplastic syndromes admitted in our hospital from April of 2014 to April of 2017 were enrolled in MDS group. And 50 healthy people who received healthy physical examination in our hospital were selected as the control group at the same period. According to the type of disease, the MDS group was divided into 4 subgroups: A, B, C, D. the serum levels of bFGF, and IL-32 were detected, and the prognosis of patients with different MDS types was evaluated. The serum levels of bFGF and IL-32 in 4 subgroups of MDS were higher than those in the control group (P<0.05). the serum level of bFGF and IL-32 was not significanty different between subgroup A and B (P>0.05), and the serum levels bFGF and IL-32 also was no significantly different between subgroup C and D (P>0.05), but the serum levels of bFGF and IL-32 in subgroup C and D were significantly higher than those in subgroup A and B (P<0.05). The total efficiency of clinical treatment was not significantly different between subgroup A and B (P>0.05),but significantly higher than that in the other 2 subgroups (P<0.05). The serum levels of bFGF and IL-32 in MDS patients were significantly higher than that in the normal controls, while the serum levels of bFGF and IL-32 in RAEB and RAEB-t subtypes were significantly higher than that in RA and RAS. The changes of serum bFGF and IL-32 levels are positively correlative.

Effect of different doses of Astragalus membranaceus on levels of vascular endothelial growth factor and basic fibroblast growth factor in serum and lung tissues of rats with pulmonary embolism

Objective To evaluate the effect of different doses of Astragalus membranaceus on the levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in serum and lung tissues of rats with pulmonary embolism. Methods Seventy-six clean-grade healthy male Sprague-Dawley rats, aged 8-9 weeks, weighing 140-170 g, were assigned to control group (group C, n=11) and experimental group (group E, n=65) by a random number table method.The rats with pulmonary embolism in group E were further divided into 4 subgroups using a random number table method: pulmonary embolism group (group P), low-dose Astragalus membranaceus group (group H1), median-dose Astragalus membranaceus group (group H2) and high-dose Astragalus membranaceus group (group H3). The model of pulmonary embolism was established by injecting autologous blood clots into the right jugular vein.At 1 h and 1, 2, 3, 4, 5 and 6 days after successful establishment of the model, Astragalus membranaceus 20, 40 and 60 g/kg were injected intraperitoneally in H1-3 groups, respectively, while the equal volume of normal saline was given instead in group P. The chest was opened after anesthesia on day 7, and blood samples were collected from cardiac chambers for determination of concentrations of serum VEGF and bFGF by enzyme-linked immunosorbent assay.The pulmonary specimens were obtained from the upper lobe of right lungs for determination of the expression of VEGF and bFGF mRNA (using real-time polymerase chain reaction). Results Compared with group C, the concentrations of serum VEGF and bFGF were significantly increased, and the expression of VEGF and bFGF mRNA in lung tissues was up-regulated in the other four groups (P<0.05). Compared with group P, the serum bFGF concentration was significantly increased, and the expression of VEGF and bFGF mRNA in lung tissues was up-regulated in H1-3 groups (P<0.05). Compared with group H1, the serum bFGF concentration was significantly increased, the expression of VEGF mRNA and bFGF mRNA in lung tissues was up-regulated in H2 and H3 groups (P<0.05). Compared with group H2, the expression of VEGF and bFGF mRNA in lung tissues was significantly up-regulated in group H3 (P<0.05). Conclusion Astragalus membranaceus can up-regulate the expression of VEGF and bFGF in lung tissues in a dose-dependent manner, thus improving pulmonary embolism in rats. Key words: Astragalus membranaceus; Pulmonary embolism; Vascular endothelial growth factors; Fibroblast growth factor 2

Estimation of salivary and serum basic fibroblast growth factor in treated and untreated patients with oral squamous cell carcinoma

ObjectiveThe purpose of this study was to evaluate salivary and serum basic fibroblast growth factor (bFGF) level in OSCC patients to provide a reliable biomarker for the early detection, monitoring, and prognosis of OSCC patients. Materials and methodsThe study enrolled 90 subjects, equally grouped as recently diagnosed & untreated OSCC patients (Group I), treated OSCC without any recurrence (Group II) & as control (Group III). Enzyme-linked immunosorbent assay was employed to measure bFGF concentrations in saliva and serum samples of all three groups. The results were tabulated and analyzed statistically. ResultsGroup I showed high-level of bFGF expression profile in saliva (8.80 ± 1.26 pg/ml) whereas the levels of bFGF in group II (2.69 ± 0.17 pg/ml) and Group III (3.17 ± 0.43 pg/ml) are significantly lower than group I. Serum bFGF levels were also high in group I (6.33 ± 0.81 pg/ml) and decreased significantly in group II (3.52 ± 0.45 pg/ml) however, the control group showed elevated range of levels (7.63 ± 0.88 pg/ml). ConclusionsThis study demonstrates the reliability of salivary bFGF marker as diagnostic as well as prognostic marker. Serum bFGF could also be used as prognostic marker only in Oral Squamous cell carcinoma patients.

Serum concentrations of VEGF and bFGF in the course of propranolol therapy of infantile hemangioma in children: Are we closer to understand the mechanism of action of propranolol on hemangiomas?

Propranolol has become the treatment of choice for infantile hemangiomas (IH). Neither the pathogenesis of IH nor the mechanism of action of propranolol on them are well understood. Possible explanations include the inhibition of angiogenesis by decreasing vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), induction of vascular endothelial cell apoptosis and vasoconstriction. The aim of the study was to assess serum concentrations of VEGF and bFGF in the course of propranolol therapy of IH in children, and to assess their clinical implications. The study included 51 children with IH treated with propranolol. The participants were assessed before, during and after the therapy with Hemangioma Activity Score (HAS), Doppler ultrasound (US) of the lesions, as well as VEGF and bFGF serum concentrations. All children showed clinical improvement measured in the HAS. A complete involution of the IH was reported in 32 (63%) children at the time of decision of the gradual withdrawing of propranolol, and in 28 (61%) patients at the end of the treatment (out of 46 patients present at the follow up after 1.5 months). Doppler US at the follow-up showed a complete disappearance of the blood flow in the lesion in 24 (52%) children and its reduction in 12 (26%) children. There was a significant decrease in VEGF and bFGF during and after treatment compared to pretreatment values. There was a correlation between the outcome of the Doppler US and changes in bFGF during and after treatment. Changes in VEGF during treatment did not correlate with changes in the Doppler US. Serum concentrations of VEGF and bFGF decreased during the propranolol treatment of IH, which may indicate the effect of propranolol on both. However, the statistical analysis showed their low prognostic value as biochemical markers of propranolol treatment. Clinical evaluation combined with Doppler US is the most valuable method of monitoring the therapy.

A therapeutic angiogenesis of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel sheets in a canine chronic myocardial infarction model.

This study investigated the safety and efficacy of a sustained release of basic fibroblast growth factor (bFGF) with biodegradable gelatin hydrogel sheets as therapeutic angiogenesis in canine chronic myocardial infarction (MI) models. Canine chronic MI model was induced by ligating the left anterior descending coronary artery and its diagonal branches. At 4week post-induction, we applied either saline (Control group, n = 5) or 200μg of bFGF (Treatment group, n = 6) soaked gelatin hydrogel sheets on the ischemic area of the left ventricular (LV) wall. At 6weeks after the procedure, we evaluated the efficacy by echocardiography and immunohistochemical study. There were no procedure-related adverse events or deaths. The serum bFGF level was under detectable levels in all animals at any sampling points. In terms of efficacy, echocardiographic evaluation demonstrated that fractional shortening was significantly improved in the treatment group. In addition, immunohistochemical study showed that the capillary density in the border zone of the MI area, as well as the MI area, significantly increased in the treatment group. Therapeutic angiogenesis by bFGF using biodegradable gelatin hydrogel sheets was safe, increased the capillary density, and improved LV function in canine chronic MI models.

Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study

BackgroundAngiogenesis is essential for the progression and metastatic spread of solid tumours. Expression of vascular endothelial growth factor (VEGF) has been linked to poor survival among osteosarcoma patients but the clinical relevance of monitoring blood and urine angiogenic factors is uncertain. The aim of this study was to determine the prognostic significance of blood VEGF and blood and urinary basic fibroblast growth factor (bFGF) levels in osteosarcoma patients, both at diagnosis and during treatment.MethodsPatients with localised or metastatic osteosarcoma enrolled in OS2005 and OS2006 studies between 2005 and 2011 were prospectively included in this study. VEGF and bFGF levels in serum and plasma and bFGF levels in urine were measured by ELISA at diagnosis, before surgery, and at the end of treatment. Endpoints considered for the prognostic analysis were histological response, progression-free and overall survival. Kruskal-Wallis tests were used to compare the distribution of baseline biomarker values across the different subgroups, and paired sample Wilcoxon rank tests were used to analyze changes over time. Association between biomarker levels and outcomes were assessed in multivariable models (logistic regression for histologic response, and Cox models for survival).ResultsSamples were available at diagnosis for 269 patients (54% males; age ≤ 18 years: 73%; localised disease in 68%, doubtful lung lesions in 17%, and metastases in 15%). High serum VEGF and bFGF levels were observed in respectively 61% and 51% of patients. Serum and plasma VEGF values were not strongly correlated with one another (r = 0.53). High serum and plasma VEGF levels were significantly more frequent in patients with large tumours (≥10 cm; p = 0.003 and p = 0.02, respectively). VEGF levels fell significantly during pre-operative chemotherapy (p < 0.0001). No significant correlation was found between this variation and either the histological response, progression-free survival or overall survival (p = 0.26, p = 0.67, and p = 0.87, respectively). No significant association was found between blood or urinary bFGF levels and clinical characteristics, histological response, or survival.ConclusionsLevels of VEGF and bFGF angiogenic factors are high in most osteosarcoma patients, but have no significant impact on response to chemotherapy or outcome in this large prospective series.OS 2006 trial registration numberclinicaltrials.gov NCT00470223; date of registration: May 3th 2007.

Efficacy of Ciji Hua'ai Baosheng formula on the expressions of vascular endothelial growth factor, kinase insert domain-containing receptor and basic fibroblast growth factor in mouse models of H22 hepatocellular carcinoma

OBJECTIVETo investigate the efficacy of Ciji Hua' ai Baosheng formula (CHBF) on microvessel density (MVD) and vascular endothelial growth factor (VEGF), kinase insert domain-containing receptor (KDR) and basic fibroblast growth factor (bFGF) expression in serum and tumor tissue of mice receiving chemotherapy for the treatment of H22 hepatocellular carcinoma. METHODSSixty Kunming mice were injected subcutaneously with H22 hepatoma carcinoma cell suspensions into the right anterior armpit. Seven days later, all transplanted tumor were formed and the mice were intraperitoneally injected 200 mg/kg cytoxan (CTX) to establish the models of tumor-bearing mouse chemotherapy, then they were randomly divided into model group, continuing CTX chemotherapy group (CTX group), and three CHBF (117, 58.5 and 29.25 g/kg) groups. After ten days of treatments, histology was observed, contents of VEGF, KDR and bFGF in serum and tumor tissue were measured by enzyme-linked immunosorbent assay (ELISA), VEGF and bFGF protein expression and MVD tagged by CD34 were detected by immunohistochemisty. RESULTSMVD in CHBF (117, 58.5 g/kg) and CTX groups was significantly lower than that in model group (P < 0.01); expressions of VEGF, KDR and bFGF in serum and tumor tissue in CHBF (117 g/kg) group were less than those in model group (P < 0.05; P < 0.01); the expressions of MVD, VEGF and bFGF in tumor tissue of CHBF (117 g/kg) group were also less than those in CTX group (P < 0.05; P < 0.01). CONCLUSIONCHBF can effectively reduce the expression of VEGF, KDR and bFGF in serum and tumor tissue, and decrease MVD and delay tumor progression.

Effect of IFN-α on Cytokines in Serum of Patients with Chronic Myeloid Leukemia

To investigate the effect of IFN-α on cytokines in serum of patients with chronic myeloid leukemia(CML). Fifty patients with CML from March 2012 to December 2015 in our hospital were randomly divided into routine treatment group (n=25) and combined treatment group (n=25), 30 healthy persons were selected as control (control group). The CML patients in routine treatment group were given orally hydroxyurea, the CML patients in combined treatment group were treated with recombinant human interferon α2b injection based on routine treatment (hydroxyurea plus IFN-α group). The levels of ALP, IL-6, PGE-2, MMP-2, and bFGF in serum were detected by ELISA. The cytogenetic, molecular and hematologic responses of patients in routine treatment group and combined treatment group, including patients in chronic and accelerated blastic phases were compared after 6 weeks of treatment. The servum levels of ALP, IL-6, PGE-2, MMP-2 and bFGF in CML patients with chronic and accelerated blastic phases all were higher than those in control group(P<0.05). The levels of MMP-2 and bFGF in CML patients with chronic phase were highr than those of CML patients with accelerated blastic phase (P<0.05), the levels of ALP, PGE-2 and IL-6 of patients with chronic phase were significantly lower than those of patients in accelerated blastic phase (P<0.05). The ALP, IL-6, PGE-2, MMP-2 and bFGF levels in combined treatment group were significantly lower than those in the routine treatment group after 2 weeks and 6 weeks of treatment(P<0.05); After the end of treatment, the CHR of routine treatment group was 56%, which was lower than that of combined treatment group 84%(χ2=18.667, P<0.001); the CCyR of routine treatment group was 32% which was significantly higher than 12% in combined treatment group(χ2=11.655, P<0.001); the CMR of routine treatment group was 12% that was significantly higher than 4% in combined treatment group (χ2=4.347, P=0.037). The median survival time of routine treatment group was significantly shorter than that of the combined treatment group, but there was no significant difference during follow-up (P>0.05). IFN-α can alleviate the symptoms of patients with CML and inhibit the process of disease with CML patients, effectively inhibit the expression of disease-related cytokines.

Serum Basic Fibroblastic Growth Factor Levels in Children with Infantile Hemangioma.

To determine serum levels of basic fibroblastic growth factor (b-FGF) in hemangioma patients under 2 y of age. The study group consisted of 43 children with infantile hemangioma and b-FGF levels were analyzed using ELISA. The serum b-FGF levels were higher in hemangioma patients than in healthy control individuals (p 0.01). There were no differences between the lesion size, number of lesions, patient age and serum b-FGF levels. Thus, b-FGF is an important growth factor that plays a central role in hemangioma, but determining b-FGF serum levels was not helpful in distinguishing between patients who require treatment and those who do not.

The effects of mycophenolate mofetil on cytokines and their receptors in pulmonary arterial hypertension in rats

Objectives: To analyse the effects of mycophenolate mofetil (MMF) on pulmonary artery pressure (PAP) and the expression of cytokines and their receptors in a rat model of pulmonary arterial hypertension (PAH).Method: Thirty-eight healthy male inbred Sprague–Dawley rats were divided randomly into four groups: a control group, a monocrotaline (MCT) group, an MMF20 group (MCT + 20 mg/kg/day MMF), and an MMF40 group (MCT + 40 mg/kg/day MMF). Systolic PAP (SPAP), the right ventricular hypertrophy index (RVI), and the levels of expression of cytokines and their receptors were measured and analysed.Results: SPAP, RVI, levels of expression of basic fibroblast growth factor (bFGF) in serum and lung homogenates, alveolar arterial wall thickness, and the number of muscular arteries in the MMF20 and MMF40 groups were decreased in comparison with the MCT group.Conclusions: MMF inhibits the formation of vascular muscle and decreases SPAP and RVI by inhibition of the expression of bFGF, endothelin-1 (ET-1), and their receptors, resulting in the inhibition of smooth muscle proliferation and amelioration of PAH.

Endostar attenuates melanoma tumor growth via its interruption of b-FGF mediated angiogenesis

To develop optimal therapeutics is one of the hotspots in both clinical and basic melanoma studies. Previous studies indicate that fibroblast growth factors (b-FGF/FGF-2), an angiogenesis inducer beyond VEGF, might be a potential drug target in melanoma. As a novel anti-angiogenesis peptide drug, Endostar has shown promising therapeutic efficacy in non-small cell lung cancer. However, the effect of Endostar on b-FGF-induced angiogenesis in melanoma is unraveled. To this end, both in vivo and in vitro experiments were conducted and it was found that treatment of Endostar could inhibit tumor growth, which was accompanied by decreased micro-vessel density and serum b-FGF levels in a mouse melanoma model. In addition, treatment with Endostar in blood vessel endothelial cells could reduce their proliferation, cell migration and tube formation capacity in a dosage-dependent manner. Moreover, treatment of Endostar could also attenuate b-FGF-activated phosphorylation of p38 and ERK1/2 in HUVECs. These findings indicate that Endostar might exert its anti-tumor effect via suppressing b-FGF-induced angiogenesis and b-FGF-activated MAPK signaling pathway, suggesting that Endostar might be a potential choice for clinical melanoma treatment.

Effects of acupotomylysis on basic fibroblast growth factor and CD34 levels in rabbits with third lumbar vertebral transverse foramen syndrome.

This study observed the local tissue homogenates in rabbits with third lumbar vertebral transverse foramen syndrome and explored the mechanism of acupotomylysis in local tissue revascularization. Thirty Japanese white rabbits were randomly divided into the following 5 groups of 6 rabbits each: normal, model, acupotomy, electroacupuncture (EA), and acupotomy-EA groups. All except the normal group were comprised of animal models of third lumbar vertebral transverse foramen syndrome prepared by embedding sponge in the left third lumbar transverse process. The rabbits in the acupotomy and EA groups underwent bilateral acupotomylysis intervention; those in the acupotomy-EA group underwent acupotomylysis and EA interventions. On the 28th day after modeling, the double-antibody ELISA was used to detect b-FGF and CD34 levels in the serum and homogenates of a muscle tissue sample from the left side of the third lumbar transverse process. The b-FGF levels in local muscle homogenates were significantly higher in the modeled rabbits than in the normal rabbits (P < 0.01), and the CD34 levels in the modeled group were significantly lower than in the normal group (P < 0.01). The b-FGF and CD34 levels in the EA, acutopomy, and acutopomy-EA groups were significantly lower than those in the modeled group (P < 0.01); the CD34 levels were significantly higher in the acupotomy-EA group than in the model group (P < 0.05); and the differences among the EA, acupotomy, and acupotomy-EA groups were not significant (P > 0.05). In conclusion, acupotomylysis regulates the levels of b-FGF and CD34 levels in serum and muscle tissue as well as local tissue revascularization.

Basic fibroblast growth factor shows prognostic impact on survival in operable non-small cell lung cancer patients.

BackgroundThe important role of angiogenesis displaying in tumor development and metastasis has been generally realized. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin (ES) are critical members of angiogenesis modulating the balance between pro-angiogenenic and anti-angiogenenic factors. The aim of this study was to evaluate the circulating level of these factors in serum and explore their prognostic significance in 96 operable non-small cell lung cancer (NSCLC) patients.MethodsPre-operational serum VEGF, bFGF, and ES were determined by commercially available enzyme-link immunosorbent assay for 96 NSCLC patients and compared to a cohort of healthy controls (n = 51). Values were correlated with clinicopathological features and overall survival (OS).ResultsThe pretreatment serum levels of VEGF, bFGF and ES in NSCLC were significantly higher than in the healthy control (P < 0.001, P = 0.009 and P = 0.016, respectively). Univariate survival analysis showed that a high bFGF level correlated with shorter OS and remained an independent factor in multivariate analysis (hazard ratio [HR] = 1.918, 95% confidence interval [CI], 1.061–3.464). In the squamous subtype, a high bFGF indicated a particularly poor prognosis (HR = 2.609, 95% CI, 1.188–5.729).ConclusionsbFGF is an independent predictor of poor survival in patients with NSCLC. For patients with high serum bFGF, aggressive antitumor treatments should be given after surgery. Approaches targeting the bFGF signaling pathway should be considered as potentially promising therapeutic strategies in NSCLC, especially for the squamous subtype.

Abstract 2828: High expression of heat shock protein 27 in metastases is correlated with response to bevacizumab monotherapy in patients with metastatic melanoma

Abstract Background: Angiogenesis is a hallmark of cancer and essential for tumor growth and metastases. It is known that melanomas are often highly vascularized. The main objective of this study was to identify predictive markers of anti-angiogenic treatment in patients with metastatic melanoma who were treated with bevacizumab monotherapy in a phase II clinical trial. As previously published, this treatment is well tolerated and showed disease control (CR, PR and SD for at least 6 months) in 31% of the patients. Lactate dehydrogenase, M-stage and early hypertension are predictive markers. Methods: 35 patients were enrolled in an open-label single arm phase II clinical trial at Haukeland University Hospital, Norway, and were treated with bevacizumab 10mg/kg q14 until disease progression or intolerable toxicity (ClinicalTrials.gov: NCT00139360). Paraffin embedded tissue of primary tumors and metastases as well as blood samples were available for investigation. Tissue sections (5µm) were stained with primary antibodies for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and heat shock protein 27 (HSP27). A staining index (SI) was used to quantify expression in primary tumors and metastases, as the product of staining intensity (0: absent, 1: weak: 2: moderate, 3: strong) and area (0: no positive tumor cells, 1: &amp;lt;10% positive tumor cells, 2: 10-50% positive tumor cells, 3: &amp;gt; 50% positive tumor cells). In addition, enzyme linked immune assay (ELISA) was performed for VEGF165 in plasma samples as well as bFGF and HSP27 in serum samples. Results: 100% of the patients with high cytoplasmic HSP27 expression in metastases had either complete remission or partial response. Conversely, none of those with low HSP27 SI responded to treatment with bevacizumab monotherapy (Mann-Whitney U-test, p=0.044). All patients with high SI in primary tumors showed a non-significant trend to better treatment response. In contrast, there was no association between cytoplasmic VEGF staining index in primary tumors or metastases and response. Neither cytoplasmic nor nuclear staining for bFGF in primary tumors or metastases could predict response to treatment. Measurements of HSP27 and bFGF in serum and VEGF165 in plasma did not show any correlation to treatment response. Conclusion: High staining index of HSP27 in metastases is significantly associated with response to treatment with bevacizumab monotherapy in patients with metastatic melanoma. Citation Format: Cornelia Schuster, Lars A. Akslen, Oddbjørn Straume. High expression of heat shock protein 27 in metastases is correlated with response to bevacizumab monotherapy in patients with metastatic melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2828. doi:10.1158/1538-7445.AM2014-2828

THU0272 Pathological Correlations of Sonographic Subclinical Synovitis in Patients with Rheumatoid Arthritis in Clinical Remission

BackgroundWe recently observed that 45% of patients with RA in clinical remission had ultrasound-defined synovitis (grade 2 or higher synovial hypertrophy (SH) and power Doppler signal). These patients had greater...

Statins in Low Doses Reduce VEGF and bFGF Serum Levels in Patients with Type 2 Diabetes Mellitus

Background/Aims: Recent experimental research revealed that statins at low doses induce angiogenesis, which in turn may be related to the course of atherosclerosis. There are no clinical studies evaluating the effect of ‘low-dose' statins on serum levels of angiogenesis regulators in diabetic subjects. We aimed to explain how low doses of statins modify the serum concentrations of two potent proangiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), in patients with type 2 diabetes. Methods: Measurements of fasting glucose level, HbA_1c, 1,5-anhydro-<smlcap>D</smlcap>-glucitol and lipid profile were taken from 47 patients with type 2 diabetes treated with low doses of atorvastatin (10 mg daily) or simvastatin (10-20 mg daily), from 45 statin-free patients with type 2 diabetes and from 23 nondiabetic subjects. Measurements of VEGF and bFGF in serum were taken using the BD™ Cytometric Bead Array. Results and Conclusion: Statins used in low doses in patients with type 2 diabetes reduce the serum concentration of VEGF and bFGF which suggests antiangiogenic potential of these doses. Nevertheless, this effect could be neutralized by postprandial hyperglycemia.

Angiogenic markers: molecular targets for personalized medicine in pituitary adenoma.

Pituitary adenomas are typically slow-growing and histologically benign tumors that can occasionally behave in a malignant-like manner, invading adjacent structures or recurring after treatment. Using protein analysis methods and multiplex xMAP assays, we aimed to find out if these particular types of tumors express angiogenic markers VEGF and basic FGF (bFGF), which are associated with tumor growth and invasiveness, and quantify them in order to establish their usefulness as biomarkers. We have analysed the expression of angiogenic markers VEGF and bFGF in serum and tissue specimens from 66 pituitary adenomas (43 invasive and 23 noninvasive). For serum analysis, we used xMAP and ELISA, and for tissue analysis, we performed histopathology and immunohistochemistry. We measured the serum angiogenic factors in pituitary adenomas. The quantification methods revealed significant differences between pituitary adenoma patients and controls, for both VEGF (212.4 vs 112.5 pg/ml in controls) and bFGF (mean value of 12.6 vs 10.8 pg/ml in controls), and also differentiated between invasive and noninvasive adenomas (p < 0.05). The tissue expression of VEGF and bFGF strongly correlated with their serum level increase. Our findings can be further developed into methods for selection of patients suitable for personalized, antiangiogenic therapy.

The relationship between serum levels of angiogenin, bFGF, VEGF, and ocular involvement in patients with Behçet’s disease

The aim of this study was to investigate the possible role of angiogenin, vascular endothelial growth factor, (VEGF) and basic fibroblast growth factor (bFGF) in the pathogenesis of BD. Sixty-five patients with BD and 21 healthy control subjects were included in the study, and serum angiogenin, bFGF, and VEGF concentrations were measured by using in-vitro enzyme immunoassay (ELISA) kits according to the manufacturer's instructions. The median serum angiogenin level was significantly higher in patients with BD (391.8; range:151.6-594.8pg/ml) than controls (298.8; range:241.9-449.6pg/ml) (p = 0.001). The levels were similar in both ocular and non-ocular BD patients (p = 0.537). The mean serum bFGF level was higher in patients with BD (38.8 ± 12.3pg/ml) than controls (33.2 ± 11.3pg/ml); the median serum VEGF level was also higher in BD patients (239.7; range:53-991.3pg/ml) than controls (189.4; range:53.6-357.9pg/ml). But these differences were not statistically significant. Serum bFGF and VEGF levels were also not different statistically in ocular and non-ocular Behçet's patients. There was no statistically significant relationship between serum angiogenin, bFGF, and VEGF levels and the presence of active eye disease or anatomic location of uveitis. While there was a correlation of borderline significance in angiogenin levels between the patients with anterior uveitis and panuveitis (p = 0.053), we did not obtain any correlation between serum angiogenin, bFGF, and VEGF levels and the duration of BD. This study suggests that angiogenin may be associated with pathophysiology of BD, and highlights the need of further investigation of the role of angiogenin, bFGF, and VEGF serum levels in BD susceptibility and its clinical manifestations.