Basic Fibroblast Growth Factor Levels Research Articles

Serum basic fibroblast growth factor levels correlate with the ultrasound measurements of bowel wall thickness (BWT) in Crohn's disease (CD)

Serum basic fibroblast growth factor levels correlate with the ultrasound measurements of bowel wall thickness (BWT) in Crohn's disease (CD)

Elevated serum vascular endothelial growth factor and basic fibroblast growth factor levels in patients with thymic epithelial neoplasms.

Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors, among which vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are considered to exert potent angiogenic activity. In this study, we investigated whether serum VEGF and bFGF levels could be predictors of the development and extension of thymic epithelial neoplasms. The subjects of this study were 37 patients with thymoma, 6 with thymic carcinoma, and 23 healthy volunteers. Serum samples were collected before clinical treatment. Serum VEGF levels were significantly (P < 0.05) elevated in the patients with thymic carcinoma (1,080 +/- 1,185pg/ml) compared with those in the healthy volunteers (407 +/- 589 microg/ml). Serum bFGF levels were also significantly (P < 0.05) elevated in the patients with thymic carcinoma (2740 +/- 631 pg/ml) compared with those in the healthy volunteers (1728 +/- 1,192 pg/ml). However, the serum VEGF and bFGF levels did not significantly differ between the patients with thymoma and the healthy volunteers. Serum VEGF and bFGF levels did not significantly differ according to the stage and pathological subtype of thymoma. Moreover, there was no correlation between the serum levels of VEGF and those of bFGF. Thus, while serum VEGF and bFGF levels may serve as markers for thymic epithelial tumors, it is unlikely that circulating VEGF and bFGF could be used as markers for assessing the progression of thymoma tumors.

Levels of basic fibroblast growth factor, glutamine synthetase, and interleukin-6 in subretinal fluid from patients with retinal detachment

PURPOSE: To investigate the presence of basic fibroblast growth factor, glutamine synthetase activity, and interleukin-6 in subretinal fluid from patients with retinal detachment. METHODS: In a prospective study we measured basic fibroblast growth factor, glutamine synthetase activity, interleukin-6, and total protein in subretinal fluid samples from 96 eyes from 94 consecutive patients with a retinal detachment corrected by a conventional scleral buckling operation in our clinical practice. As controls, vitreous fluid samples from eyes with a macular hole (n = 6) or pucker (n = 11) were used. Laboratory data of the patient group were compared with the control group and correlated with various clinical data. RESULTS: Levels (median, range) of basic fibroblast growth factor, glutamine synthetase activity, interleukin-6, and total protein were significantly higher in patients than in controls ( P < .0001). An increased level of glutamine synthetase and total protein correlated with a longer duration of the retinal detachment (r = .4, P = .002, and r = .34, P = .001, respectively). Interleukin-6 and basic fibroblast growth factor levels did not correlate with the duration of the detachment. After multivariate logistic regression analysis, no significant relation was found between any of the tested subretinal proteins and a low visual outcome or redetachment. CONCLUSIONS: We found increased levels of basic fibroblast growth factor and glutamine synthetase in subretinal fluid from patients with retinal detachment. Basic fibroblast growth factor and glutamine synthetase may play a role in the pathogenesis and recovery after retinal detachment. The questions of whether the increased levels of basic fibroblast growth factor and glutamine synthetase result from leakage of dying glia cells (including Müller cells) and neurons and if basic fibroblast growth factor is actively produced to protect the photoreceptor cells need further research.

Correlation of serum basic fibroblast growth factor levels with clinicopathologic features and postoperative recurrence in hepatocellular carcinoma

Background: Basic fibroblast growth factor (bFGF) is an important positive regulator of tumor angiogenesis. This study evaluated the role of serum bFGF as a biological marker of tumor invasiveness and postresection recurrence in hepatocellular carcinoma (HCC). Methods: Concentrations of bFGF in preoperative serum samples in 88 patients undergoing resection of HCC were measured by a quantitative enzyme-linked immunosorbent assay. A single pathologist performed histopathologic examination of all tumor specimens. All patients were prospectively monitored for tumor recurrence. Results: The preoperative serum bFGF levels ranged from <0.22 to 71.2 pg/mL (median 10.8 pg/mL). There was significant correlation between high serum bFGF levels and large tumor >5 cm, presence of venous invasion or advanced pTNM stage. Patients with a serum bFGF level >10.8 pg/mL had worse disease-free survival than those with a level <10.8 pg/mL (median disease-free survival 11.2 versus 20 months, P = 0.044). Serum bFGF level >10.8 pg/mL ( P = 0.035) and tumor size >5 cm ( P = 0.004) were independent preoperative factors that predicted early recurrence after resection of HCC. Conclusions: This study supports a role of bFGF in tumor growth and invasion in HCC. A high preoperative serum bFGF level appears to be predictive of invasive tumor and early postoperative recurrence. The clinical implications of serum bFGF level in HCC warrant further investigation.

Changes in astrocytic basic fibroblast growth factor expression during and after prolonged exposure to escalating doses of amphetamine

We have shown that brief exposure to amphetamine leads to sustained glutamate-dependent increases in expression of the neurotrophic, neuroprotective factor, basic fibroblast growth factor, in astrocytes in dopaminergic cell body regions and that blockade of basic fibroblast growth factor in this region prevents the development of behavioral sensitization to amphetamine. Here we examine the effects of prolonged exposure to an escalating-dose regimen of amphetamine known to induce long-lasting sensitization to amphetamine and leading to increases in neuronal dendritic length and spine density in nucleus accumbens and prefrontal cortex and to decreases in spine density in occipital cortex. Astrocytic basic fibroblast growth factor immunoreactivity was increased in both dopaminergic cell body and terminal regions one week after termination of a two-week amphetamine treatment (1–4 mg/kg). These effects were not evident one week after a five-week treatment (1–9 mg/kg) and, in fact, one month later basic fibroblast growth factor levels in cell body regions were decreased. In the occipital cortex, basic fibroblast growth factor immunoreactivity was decreased one week after the two-week amphetamine treatment, but was not different from that seen in saline-treated animals after the five-week treatment. Increased astrocytic basic fibroblast growth factor expression appears to be an early, but relatively prolonged, response to amphetamine exposure and seems to parallel structural changes induced by repeated drug exposure. These findings suggest that basic fibroblast growth factor may participate in the development of structural changes brought about by amphetamine. The fact that the basic fibroblast growth factor response is not maintained after prolonged intense exposure to amphetamine suggests that the factors that initially induce basic fibroblast growth factor expression are self-regulating.

Vascular endothelial growth factor and basic fibroblast growth factor in children with cyanotic congenital heart disease

Objective: Vascular endothelial growth factor and basic fibroblast growth factor are potent stimulators of angiogenesis. Children with cyanotic congenital heart disease often experience the development of widespread formation of collateral blood vessels, which may represent a form of abnormal angiogenesis. We undertook the present study to determine whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor and basic fibroblast growth factor. Methods: Serum was obtained from 22 children with cyanotic congenital heart disease and 19 children with acyanotic heart disease during cardiac catheterization. Samples were taken from the superior vena cava, inferior vena cava, and a systemic artery. Vascular endothelial growth factor and basic fibroblast growth factor levels were measured in the serum from each of these sites by enzyme–linked immunosorbent assay. Results: Vascular endothelial growth factor was significantly elevated in the superior vena cava (P = .04) and systemic artery (P = .02) but not in the inferior vena cava (P = .2) of children with cyanotic congenital heart disease compared to children with acyanotic heart disease. The mean vascular endothelial growth factor level, determined by averaging the means of all 3 sites, was also significantly elevated (P = .03). Basic fibroblast growth factor was only significantly elevated in the systemic artery (P = .02). Conclusion: Children with cyanotic congenital heart disease have elevated systemic levels of vascular endothelial growth factor. These findings suggest that the widespread formation of collateral vessels in these children may be mediated by vascular endothelial growth factor. (J Thorac Cardiovasc Surg 2000;119:534-9)

Plasma vascular endothelial but not fibroblast growth factor levels correlate with colorectal liver mestastasis vascularity and volume.

The extent to which plasma levels of angiogenic factors in healthy individuals and tumour volume-related variations in colorectal cancer affect the accuracy of circulating angiogenic factors as predictors of colorectal cancer vascularity is unknown. We used enzyme-linked immunosorbant assay to measure plasma vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels in colorectal liver metastasis (CLM) patients, and ‘no cancer’ controls. CLM volume was determined from computerized tomography scans, and tumour vessel count and vessel volume from anti-endothelial antibody-stained biopsies. There was a significant (P = 0.03) increase in plasma VEGF level in 29 CLM patients (median 180.3 pg ml−1, iqr 132.5–284.8 pg ml−1) compared with 19 controls (median 125.8 pg ml−1, iqr 58.2–235.9 pg ml−1). There were significant correlations between plasma VEGF and tumour vessel count (r = 0.66, P = 0.03), tumour vessel volume (r = 0.59, P = 0.03), and CLM volume (r = 0.53, P = 0.03). A VEGF level in the upper quartile of the plasma VEGF distribution had a 70% sensitivity and 75% specificity in predicting an upper quartile liver metastasis tumour vessel count. No relation was identified between CLM and plasma bFGF levels. Plasma VEGF level predicted CLM vascularity, despite an overlap with normal levels and tumour volume-related variations. © 2000 Cancer Research Campaign

Basic fibroblast growth factor stimulates repair of wounded hepatocyte monolayer: Modulatory role of protein kinase A and extracellular matrix

The two important repair mechanisms after hepatocyte injury are proliferation and migration of the nearby healthy hepatocytes. Although previous studies have shown that basic fibroblast growth factor (bFGF) levels are markedly elevated after liver injury, the role of bFGF in the repair of the wounded hepatocytes is not well understood. The aim of this study was to delineate the role of bFGF in the repair of the wounded hepatocyte monolayers. Specifically, we examined the role of bFGF in cellular proliferation and migration of hepatocytes with an in vitro wound model. Standardized excisional wounds were created in clone 9 rat hepatocyte monolayers by a razor blade, and the extent of epithelial proliferation and migration was measured. After wound formation, bFGF (30 ng/mL) significantly stimulated proliferation of hepatocytes at the wound margin. bFGF also stimulated the migration of hepatocytes at the wound front. bFGF stimulation of hepatocyte migration correlated with increased formation of actin stress fibers and bFGF-receptor protein level. The bFGF stimulation of hepatocyte migration was abolished by various protein kinase A activating agents including 3-isobutyl-1-methylxanthine, 8-bromoadenosine-3′,5′-cyclic monophosphate, forskolin, and cholera toxin. In addition, protein kinase A activating agents almost completely prevented bFGF-induced actin stress fiber formation in the cells at the wound front. Varying the basement membrane composition of the extracellular matrix had a selective enhancing effect on the basal rates of hepatocyte migration (collagen IV ≥ laminin > collagen I > fibronectin > control (plastic). bFGF treatment resulted in a similar additive increase in hepatocyte migration across all coated surfaces studies. We conclude that bFGF promotes hepatocyte wound repair by stimulating both proliferation and migration of the hepatocyte at the margin of the wound.

Basic FGF decreases clearance receptor of natriuretic peptides in fetoplacental artery endothelium.

Atrial natriuretic peptide (ANP) is present in the fetoplacental circulation of humans and sheep. The ANP-A receptor is the specific membrane receptor for ANP, which produces cGMP. The clearance receptor of natriuretic peptide (CR) is postulated to modulate local concentrations of ANP, thereby modulating cGMP production through the ANP-A receptor. Recently we reported that fetoplacental basic fibroblast growth factor (bFGF) and cGMP levels are increased dramatically during the third trimester of ovine gestation. Therefore we hypothesized that bFGF will downregulate CR expression in cultured ovine fetoplacental artery endothelial (OFPAE) cells via the mitogen-activated protein kinase (MAPK) signal cascade mechanism, thereby causing augmentation of ANP-mediated cGMP production. Western analysis and/or RT-PCR of CR expression were performed after treatment of OFPAE cells with bFGF (10 pg/ml-1 microgram/ml) with or without 50 microM PD-98059, a selective inhibitor of MAPK kinase. To investigate the possible effects of CR downregulation on the functional modulation of ANP-A receptor activation, cGMP production (20 min) by OFPAE cells was measured in response to ANP (10 pM-1 microM) with or without pretreatment (24 h) of 10 ng/ml bFGF. CR expression in OFPAE cells was dose dependently downregulated by 1-10 ng/ml bFGF treatment (maximum -69%), which was completely reversed by pretreatment with PD-98059. Treatment of OFPAE cells with 10 ng/ml bFGF (24 h) did not alter maximum ANP-A activity (cGMP production/20 min), but decreased the apparent ED(50) of ANP to stimulate cGMP production from 2.5 to 0.83 nM, suggesting the possibility that bFGF-mediated downregulation of CR may elevate ANP-mediated cGMP production responses. Thus bFGF downregulates CR mRNA and protein expressions via the MAPK cascade in OFPAE cells.

Angiogenic growth factors and endostatin in non-Hodgkin's lymphoma.

A number of clinical studies have demonstrated the prognostic significance of angiogenesis and angiogenic growth factors in solid tumours; however, very little is known about the relevance of these parameters in haematological malignancies. We evaluated circulating levels of angiogenic growth factors and endostatin in 36 non-Hodgkin's lymphoma (NHL) patients. Baseline vascular endothelial growth factor (VEGF) levels of patients in complete remission (CR) after a median follow-up of 21 months were significantly lower than those of patients with progressive disease (P = 0.016). Event-free survival (EFS) rate was significantly higher in patients who had baseline VEGF and basic-fibroblast growth factor (b.FGF) levels below the median values of 147 and 19.5 pg/ml (P = 0.018 and 0.039 by log-rank test, respectively). Conversely, the levels of endostatin, angiogenin and leptin were not different in CR patients compared to relapsed patients and did not correlate with EFS. Our data suggest that b-FGF and, particularly, VEGF might be considered prognostic factors in NHL staging and management.

Expression of basic fibroblast growth factor and its receptor in angiosarcoma

Angiosarcoma, a rare aggressive malignant tumor thought to be of vascular origin with high potential for metastasis, frequently occurs on the scalp of elderly people. Recent findings have shown that overexpression of basic fibroblast growth factor and its receptor is associated with neoplasia, which suggests that basic fibroblast growth factor promotes tumor vascularization and subsequent growth. In this study, we examined the immunohistologic localization of basic fibroblast growth factor and its receptor in angiosarcoma. Our results suggest that basic fibroblast growth factor synthesized in the tumor endothelial cells plays an important role in the growth and progression in angiosarcoma and that serum basic fibroblast growth factor levels are elevated in patients with nodular type angiosarcoma. (J Am Acad Dermatol 1999;41:127-9.)

Ocular Neovascularization: Clarifying Complex Interactions

Neovascularization within the eye contributes to visual loss in several ocular diseases, the most common of which are proliferative diabetic retinopathy, neovascular age-related macular degeneration, and retinopathy of prematurity. Together, these three diseases afflict persons in all stages of life from birth through late adulthood and account for most instances of legal blindness. Retinopathy of prematurity (ROP) occurs in premature neonates. Normally, the retina becomes completely vascularized at full term. In the premature baby, the retina remains incompletely vascularized at the time of birth. Rather than continuing in a normal fashion, vasculogenesis in the premature neonatal retina becomes disrupted. Abnormal new proliferating vessels develop at the juncture of vascularized and avascular retina. These abnormal new vessels grow from the retina into the vitreous, resulting in hemorrhage and tractional detachment of the retina. Although laser ablation of avascular peripheral retina may halt the neovascular process if delivered in a timely and sufficient manner, some premature babies nevertheless go on to develop retinal detachment. Surgical methods for treating ROP-related retinal detachments in neonates have limited success at this time because of unique problems associated with this surgery, such as the small size of the eyes and the extremely firm vitreoretinal attachments in neonates. Diabetic retinopathy is the leading cause of blindness in adults of working age. In persons with diabetes mellitus, retinal capillary occlusions develop, creating areas of ischemic retina. Retinal ischemia serves as a stimulus for neovascular proliferations that originate from pre-existing retinal venules at the optic disk or elsewhere in the retina posterior to the equator. Severe visual loss in proliferative diabetic retinopathy (PDR) results from vitreous hemorrhage and tractional retinal detachment. Again, laser treatment (panretinal photocoagulation to ischemic retina) may arrest the progression of neovascular proliferations in this disease but only if delivered in a timely and sufficiently intense manner. Some diabetic patients, either from lack of ophthalmic care or despite adequate laser treatment, go on to sustain severe visual loss secondary to PDR. Vitrectomy surgery can reduce but not eliminate severe visual loss in this disease. Age-related macular degeneration is the leading cause of severe visual loss in persons over 65 years old. In contrast to ROP and PDR, in which neovascularization emanates from the retinal vasculature and extends into the vitreous cavity, AMD is associated with neovascularization originating from the choroidal vasculature and extending into the subretinal space. Choroidal neovascularization causes severe visual loss in AMD patients because it occurs in the macula, the area of retina responsible for central vision. The stimuli which lead to choroidal neovascularization are not understood. Laser ablation of the choroidal neovascularization may stabilize vision in selected patients. However, only 10% to 15% of patients with neovascular AMD have lesions judged to be appropriate for laser photocoagulation according to current criteria. Retinopathy of prematurity, proliferative diabetic retinopathy, and neovascular age-related macular degeneration are but three of the ocular diseases which can produce visual loss secondary to neovascularization. Others include sickle cell retinopathy, retinal vein occlusion, and certain inflammatory diseases of the eye. These, however, account for a much smaller proportion of visual loss caused by ocular neovascularization. Additional treatments beyond laser photocoagulation and vitrectomy surgery are needed to improve outcomes in these patients. Pharmacological antiangiogenic therapy can potentially assist in prevention of the onset or progression of ocular neovascularization and is a current goal of many research laboratories and pharmaceutical companies.

ANGIOGENESIS IN TWO HUMAN PROSTATE CANCER CELL LINES WITH DIFFERING METASTATIC POTENTIAL WHEN GROWING AS SOLID TUMORS IN NUDE MICE

Purpose Angiogenesis, typically a feature of aggressive tumors, is frequently associated with increased vascular endothelial growth factor (VEGF) production. Here, angiogenesis and angiogenic growth factor expression were assessed in two human prostate cancer cell models with differing metastatic potential. Method Prostatic tumors were obtained by injecting either highly metastatic PC-3M cells or poorly metastatic DU145 cells into the surgically exposed prostate glands of nude mice. Angiogenesis was evaluated by immunohistochemical staining, and tumor VEGF, transforming growth factors-beta (TGF-beta 1 and TGF-beta 2), and basic fibroblast growth factor (bFGF) levels were determined by immunoassays (ELISAs). VEGF isoforms were detected by Western blotting in both solid tumor extracts, and in culture medium conditioned by the same cell lines (CM). Results Angiogenesis was much more evident in PC-3M tumors (vessel counts: PC-3M tumors 360 +/- 42, DU145 tumors 156 +/- 25; p = 0.003), but ELISA-determined VEGF levels were approximately 3-fold higher in both DU145 cell tumors, and in DU145 cell CM. However, Western blotting showed that PC-3M tumors, but not CM, contained VEGF isoforms with molecular weights of 43 and 57 kDa. TGF-beta 2, but not TGF-beta 1 concentrations were higher in DU145 cell tumors (p <0.001); bFGF levels were higher in the PC-3M cell tumors (p <0.05). Conclusions When growing in nude mouse prostate glands, the PC-3M cell line provides a model for the angiogenic activity associated with aggressive prostate cancer. This is accompanied by the expression of immunoreactive VEGF which is not detected by an ELISA antibody raised against the conventional VEGF 165, but appears on Western blots as what may prove to be novel high molecular weight species. Observed differences in TGF-beta 1 and -beta 2, and bFGF expression, may also be associated with an angiogenic phenotype.

Influence of pregnancy on gene expression in rabbit articular cartilage

Objective: Articular cartilage is known to be influenced by estrogen and the pregnancy-associated hormone, relaxin,in vitro. Such observations have raised the possibility that articular cartilage in females may be subjected to unique regulatory influences by such hormonesin vivo. The purpose of this study was to evaluate mRNA levels for several relevant molecules in the articular cartilage of pregnant and non-pregnant rabbits.Design: Total RNA was extracted from New Zealand White rabbit knee articular cartilage using the TRIspin method. The total RNA was reverse transcribed and analysed by the sensitive molecular technique of semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) using rabbit specific primer sets.Results: Total RNA yield from articular cartilage from primigravida rabbits was reduced to 65% of age-matched control values (P=0.0003); however the yield from multiparous animals was not significantly depressed. In both cases, DNA yields were not affected by pregnancy. There was a general tendency for depressed mRNA levels for most genes investigated in cartilage from pregnant animals. Articular cartilage from multiparous rabbits showed a significant decrease in mRNA levels for relevant molecules such as type II collagen, biglycan, collagenase and tissue inhibitors of metalloproteinases (TIMP)-1, as well as necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and cyclo-oxygenase 2 (COX-2). Transcripts for collagenase and lumican were significantly lower in cartilage from primigravida rabbits. Transforming growth factor β1 (TGF-β1) transcript levels were significantly decreased in both pregnant groups. In contrast, basic fibroblast growth factor (bFGF) and insulin-like growth factor-2 (IGF-2) mRNA levels were significantly decreased in cartilage from primigravida rabbits, whereas transcripts for these molecules were upregulated in the cartilage of multiparous rabbits.Conclusions: The present study demonstrates that regulation of RNA levels in articular cartilage during pregnancy is complex and is influenced by the parity and/or the skeletal maturity of the animals.

Induction of Interleukin-1 Associated with Compensatory Dopaminergic Sprouting in the Denervated Striatum of Young Mice: Model of Aging and Neurodegenerative Disease

Young mice challenged with the neurotoxin 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), which selectively destroys the substantia nigra dopaminergic neurons in the midbrain, exhibit spontaneous recovery of dopaminergic nerve terminals. However, such recovery becomes attenuated with age. Here we report that newly sprouted fibers originate from spared dopaminergic neurons in the ventral tegmental area. We found that interleukin-1 (IL-1), an immune response-generated cytokine that can enhance dopaminergic sprouting when exogenously applied, increased dramatically in the denervated striatum of young mice (2 months) compared with middle-aged mice (8 months) after MPTP treatment. Young mice displayed a maximal 500% induction of IL-1alpha synthesis that remained elevated for several weeks in the dorsal and ventral striatum, whereas middle-aged mice exhibited a modest 135% induction exclusively in the dorsal striatum for a week. IL-1alpha immunoreactivity was localized in GFAP-immunoreactive hypertrophied astrocytes and neurons within the denervated striatum of young mice. However, no induction of IL-1alpha mRNA was seen in the midbrain in either age group despite glial activation. Because we have reported that IL-1 can regulate astroglia-derived dopaminergic neurotrophic factors, it was surprising that no changes were observed in acidic and basic fibroblast growth factor or glial cell line-derived neurotrophic factor mRNA levels associated with MPTP-induced plasticity of dopaminergic neurons in the striatum of young mice. Interestingly, we found that dopaminergic neurons express IL-1 receptors, thus suggesting that IL-1alpha could directly act as a target-derived dopaminergic neurotrophic factor to initiate or enhance the sprouting of dopaminergic axonal terminals. These findings strongly suggest that IL-1alpha could play an important role in MPTP-induced plasticity of dopaminergic neurons.

Basic Fibroblast Growth Factor: Peritoneal and Follicular Fluid Levels and its Effect on Early Embryonic Development

Objective: To investigate the effect of basic fibroblast growth factor (FGF) on preimplantation embryos and to evaluate the levels of basic FGF in follicular and peritoneal fluid.Design: Prospective study.Setting: University-based laboratory.Patient(s): Follicular fluids (FFs) were obtained from women undergoing ovulation induction (n = 62) and peritoneal fluids were obtained from women with (n = 49) or without (n = 12) endometriosis.Intervention(s): The effect of basic FGF on mouse embryos was assessed. Basic FGF concentrations were measured in pre-hCG and post-hCG FFs and in peritoneal fluids.Main Outcome Measure(s): Two-cell murine embryos were treated with basic FGF and followed for the rate of blastocyst formation and embryo hatching. Follicular and peritoneal fluid basic FGF levels were measured by ELISA.Result(s): Basic FGF (10 ng/mL) decreased the rate of blastocyst formation and embryo hatching. The level of basic FGF did not change in the FF around ovulation, and there was no correlation between FF basic FGF levels and reproductive parameters, with the exception of age. The levels of basic FGF in the peritoneal fluid of women with or without endometriosis were not different.Conclusion(s): Basic FGF is present in follicular and peritoneal fluids, but its concentration in these fluids does not change during the menstrual cycle or in the presence of endometriosis. Basic FGF inhibits murine preimplantation embryonic development at concentrations 10–100 times higher than the levels detected in follicular and peritoneal fluids.

CYTOKINE LEVELS IN CYSTIC RENAL MASSES ASSOCIATED WITH RENAL CELL CARCINOMA

Purpose We compared cytokine levels in fluid from renal cysts with and without renal cell carcinoma. Materials and Methods Fluid was aspirated from 18 renal cysts without (benign) and 21 with renal cell carcinoma (malignant). Serum from patients with renal cell carcinoma and healthy controls was collected and cytokines were measured by enzyme-linked immunosorbent assay. Results Interleukin-6 (IL-6) and basic fibroblast growth factor concentrations were higher in malignant than benign cysts or serum (p <0.006). Epidermal growth factor levels were significantly higher in malignant cysts and serum than in benign cysts (p <0.01). IL-6 levels in malignant cysts positively correlated with the erythrocyte sedimentation rate (R = 0.80) and C-reactive protein (R = 0.86), and they were higher in grade 3 than in grade 2 tumors. Basic fibroblast growth factor levels were significantly higher in malignant cysts associated with hypervascular than hypovascular tumors (p = 0.029). Conclusions Cytokine levels in aspirated fluid may help to identify malignant renal cysts and indicate the characteristics of coexisting tumors.

Urinary Basic Fibroblast Growth Factor

Angiogenesis is a prominent histopathologic feature of preosseous fibroproliferative lesions in patients who have fibrodysplasia ossificans progressiva. Basic fibroblast growth factor is an extremely potent in vivo stimulator of angiogenesis, and has been implicated in the growth of solid tumors. An enzyme linked immunosorbent assay for basic fibroblast growth factor was performed on urine samples from patients who had active (n = 28) and inactive (n = 39) fibrodysplasia ossificans progressiva, and compared with urine samples from normal age and gender matched control subjects (n = 54). Median basic fibroblast growth factor levels were 2705 pg/g of creatinine in the normal control group, 5058 pg/g of creatinine in patients with inactive fibrodysplasia ossificans progressiva (no significant difference), and 8793 pg/g of creatinine in patients with active fibrodysplasia ossificans progressiva. Female subjects, both normal and with fibrodysplasia ossificans progressiva, had higher levels of urinary basic fibroblast growth factor than did male subjects. There was no correlation of urinary basic fibroblast growth factor levels with age or severity of preexisting disability. These data document an elevation of urinary basic fibroblast growth factor during acute flareups of fibrodysplasia ossificans progressiva and provide a biochemical basis for considering antiangiogenic therapy for inhibiting endochondral osteogenesis in this disorder.

Marked elevation of vascular endothelial growth factor and basic fibroblast growth factor in pericardial fluid of patients with angina pectoris.

Although we reported that basic fibroblast growth factor (bFGF) levels in pericardial fluid of patients with unstable angina are apparently increased, it was unclear whether vascular endothelial growth factor (VEGF) is also increased in patients with myocardial ischemia. Using an enzyme-linked immunosorbent assay, we measured the concentrations of VEGF and bFGF in pericardial fluid of 51 patients with open heart surgery. Patients were divided into group A (n=10) with class III unstable angina (Braunwald's classification), group B (n=24) with class I or II unstable angina or stable angina and group C (n=17) with non-ischemic heart disease. The VEGF level in pericardial fluid in group A was 83+/-7 pg/ml, being significantly (p<0.001) higher than the 27+/-3 pg/ml in group B and the 28+/-5 pg/ml in group C. The concentrations of bFGF in pericardial fluid in groups A and B were 1461+/-579 and 1224+/-161 pg/ml, respectively, significantly (p<0.05) higher than the 292+/-97 pg/ml in group C. The level of VEGF in pericardial fluid was increased only in patients with severe rest angina within 2 days before emergency coronary artery bypass graft surgery (CABG), while bFGF was increased in all patients undergoing CABG for coronary artery disease. Thus VEGF and bFGF may play important roles in mediating collateral growth in humans.

Basic Fibroblast Growth Factor in the Urine of Children with Voiding Pathology

Purpose Basic fibroblast growth factor is a mediator of tissue response to injury. Voiding pathology often results in bladder abnormalities. We prospectively determined whether basic fibroblast growth factor is elevated in the urine of children with bladder dysfunction compared to that of normal controls. Materials and Methods A total of 97 consecutive children with myelomeningocele and 32 with voiding pathology due to other etiologies underwent urodynamic testing, and 11 children with no bladder symptoms and sterile urine served as controls. Urinary basic fibroblast growth factor levels were assayed by enzyme-linked immunosorbent assay and normalized to urinary creatinine. Results Mean urinary basic fibroblast growth factor was higher in bladder dysfunction from myelomeningocele (6,673 pg./gm. creatinine, p = 0.0015) and other etiologies (5,665 pg./gm. creatinine, p = 0.0025) compared with urine from normal bladders (2,995 pg./gm. creatinine). In the myelomeningocele group urinary tract infection was associated with higher urinary basic fibroblast growth factor than in sterile urine (9,214 versus 5,642 pg./gm. creatinine, p = 0.018). Patient age, gender, remote bladder surgery, clean intermittent catheterization, detrusor hyperreflexia, detrusor compliance, age adjusted pressure specific bladder volume, low grade reflux and degree of trabeculation did not correlate with levels of basic fibroblast growth factor (p >0.05). Conclusions Urinary elevation of basic fibroblast growth factor, a critical mediator of wound repair, in children with voiding pathology and clinically abnormal bladders supports the paradigm that bladder dysfunction may result from generalized response-to-injury mechanisms. The role of fibrogenic cytokines, such as basic fibroblast growth factor, merits further directed investigation in bladder pathology.