Serum Levels Of Growth Factors Research Articles

Serum levels of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs), -1, -2, -3, in oral cancer

Introduction Insulin-like growth factor (IGF) possesses mitogenic properties promoting cellular proliferation and inhibiting cellular apoptosis. Reported evidence suggests that cancer (non-oral) is associated with high circulating levels of IGF-1 and low levels of IGFBP-3. Aims This study measured circulating levels of IFG-1 and IGFBPs -1, -2 and -3 in oral cancer patients. Methodology Blood was collected from surgical patients and controls. Samples were assayed for IGF-1 and IGFBPs -1, -2, -3, using commercially available enzyme-linked immunosorbant assays (ELISA; R&D Systems Europe, Oxon, UK). Results Twenty-seven oral cancer and 31 age- and sex-matched patients were recruited. Mean IGF-1 and IGFBP-3 levels were significantly lower in cancer patients than controls (85.3 ng/ml and 2008 ng/ml versus 191 ng/ml and 2935 ng/ml, P < 0.001). In contrast, levels of IGFBPs 1 and 2 were significantly higher in cancer patients than in controls. No significant association was demonstrated with tumour size or nodal metastases. Discussion This study has shown that in contrast to other cancers, circulating levels of IGF-1 and IGFBP-3 may both be lowered in patients with head and neck cancer.

Vascular endothelial growth factor levels in serum and plasma from patients undergoing controlled ovarian hyperstimulation for IVF

Vascular endothelial growth factor (VEGF) has been investigated as a marker of ovarian response to controlled ovarian hyperstimulation and as a predictor of ovarian hyperstimulation syndrome (OHSS) in IVF cycles. In most studies, serum has been used for circulating VEGF concentration measurement, but it has been suggested that plasma is the preferred medium to measure VEGF levels because of the potential contribution of VEGF released from platelets during blood clotting. This study investigated VEGF concentrations in paired serum and plasma samples from patients undergoing controlled ovarian hyperstimulation for IVF. Serum and plasma VEGF levels, as well as the number of platelets, were measured in 30 IVF patients who comprised three study groups delineated according to the estradiol (E(2)) serum concentration reached on the day of HCG administration: 10 patients having low E(2) serum levels (<1500 pg/ml, group L), 10 patients having intermediate E(2) serum levels (1500-3000 pg/ml, group I) and 10 patients having high E(2) serum levels (>3000 pg/ml, group H). There was a statistically significant correlation between plasma and serum VEGF levels (rho = 0.61; P < 0.005) for the entire population studied, although serum values were higher by a factor of approximately 6-fold. No significant correlation was found between peripheral blood VEGF concentrations and serum E(2) or follicle number on HCG day or the number of oocytes collected. Similarly, paired serum and plasma VEGF measurements did not correlate with platelet count. Serum and plasma VEGF concentrations are strongly correlated in paired samples from infertile patients undergoing controlled ovarian hyperstimulation. However, neither serum nor plasma VEGF levels were correlated with parameters associated with ovarian follicular activity. Peripheral blood VEGF levels were not correlated with platelet count.

Nerve growth factor serum concentrations rise after successful cognitive–behavioural therapy of generalized anxiety disorder

Generalized anxiety disorder (GAD) is a chronic stress disease with permanent physical tension and cognitive strain. Raised nerve growth factor (NGF) serum levels were reported as an acute stress reaction in soldiers before their first parachute jump even before the rise in cortisol. Taking GAD as a clinical model of chronic stress, we measured NGF in the serum of 22 patients with GAD before and after cognitive–behavioural therapy (CBT) and compared them to those of healthy normal controls. Treatment response was tested by the values of the State and Trait of Anxiety Inventory (STAI) and the Hamilton Anxiety Scale (HAM-A) as treatment outcome variables. The NGF values of patients and controls were similar at baseline ( p = 0.8941); however, with successful treatment, corresponding to a mean reduction in the HAM-A by more than 50% and a reduction in the clinical global impression scale (CGI) median from 4 to 1, the patients' NGF serum concentrations rose significantly ( p = 0.0006) which might correspond to an altered stress reaction, possibly contributing to good therapeutic response with CBT. There were 3 patients with a HAM-A decrease of less than 15%. In those patients NGF rose only marginally. Hence, the increase in serum NGF seems to indicate good treatment response.

Do Serum Angiogenic Growth Factors Provide Additional Information to That of Conventional Markers in Monitoring the Course of Metastatic Breast Cancer?

Objective:Our work evaluated the potential role of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) serum levels with respect to that of conventional serum tumour markers, CEA and CA 15-3, in monitoring the course of metastatic breast cancer in 56 female patients treated with cytotoxic chemotherapy. Methods: VEGF and bFGF concentrations were determined using a quantitative sandwich enzyme immunoassay technique. The positive predictive value (PPV) of each marker and of marker combinations for different types of clinical response was calculated. Results: The highest PPV for overall disease control was shown by bFGF (70%), which also showed the highest PPV for both partial response (36.4%) and stable disease (63.2%). CEA showed the highest predictive value for progression (69.2%). A combined increase in CEA and bFGF or VEGF was associated with disease progression in all patients. Conclusions:Information provided by angiogenic factor levels seems to be independent of and is possibly complementary to that provided by conventional serum markers. bFGF showed the maximum predictive value for disease control and provided additional information to that obtained from CEA or CA 15-3 evaluation. It could therefore be a promising candidate for monitoring response to chemotherapy in advanced breast cancer.

Vascular Endothelial Growth Factor-D Is Increased in Serum of Patients with Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare destructive lung disease characterized by an abnormal proliferation of smooth muscle-like cells (LAM cells) in the lung and along the axial lymphatics. LAM demonstrates a heterogeneous clinical course, but there is no serum surrogate marker available for assessing the disease severity or predicting the disease progression. Since the authors have recently demonstrated the extensive LAM-associated lymphangiogenesis and its potential role in progression and metastasis of LAM cells, they hypothesized that serum levels of lymphangiogenic growth factors might be increased in LAM and become a surrogate marker for disease severity. VEGF-A, VEGF-C, and VEGF-D in serum of 44 patients with LAM were measured by enzyme-linked immunosorbant assay. Only VEGF-D was significantly increased in LAM patients as compared with age- and gender-matched healthy volunteers (n=24) (LAM vs. control, geometric mean 95% CI; 1069.3 pg/mL (809.4 approximately 1412.6) vs. 295.9 pg/mL (262.6 approximately 333.5), p<0.0001). Serum VEGF-D levels negatively correlated with variables of pulmonary function tests, FEV1/FVC (forced expiratory volume in one second/forced vital capacity) (r=-0.365, p<0.05) and %DLco/VA (the percentage of diffusing capacity for carbon monoxide/alveolar volume to the predicted value) (r=-0.560, p<0.001). As expected, the group who received hormone therapy showed more deteriorated pulmonary function with higher serum VEGF-D levels than the group who was just observed without hormone therapy. Immunohistochemical examination of lung specimens demonstrated the positive immunoreactivity of LAM cells for VEGF-D. Serum VEGF-D levels may be a valuable surrogate marker for evaluating the disease severity in LAM.

Postnatal decreases in cardiac muscle fractional protein synthesis rates in fed pigs measured by an intraperitoneal flooding dose of L‐[ring‐2H5]Phe

This study was conducted to quantify postnatal changes in cardiac muscle protein fractional synthesis rates (FSR) and their correlations with serum levels of hormones (nsulin, growth hormone, and cortisol), growth factors (IGF-I and GLP-2) and free amino acids (AA) in fed pigs. Thirty six purebred Yorkshire gilts were used for sampling at d 1, 4, 6, 12, 20 and 28 (1 wk post-weaning) d of age. Piglets received ip injection of a flooding dose of Phe containing L-[ring-2H5] (40 molar%) in saline. Serum samples before the injection and plasma and heart samples at 30 min post-injection were obtained for the determinations of tracer Phe enrichment by GC-MS, free AA by HPLC, and hormones and growth factors by RIA. Tracer Phe enrichments in the plasma and cardiac muscle free AA pools were 25–27 molar%. Cardiac muscle FSR was 29.5, 28.5, 27.6, 28.9, 21.8, and 11.7 %/d at d 1, 4, 6, 12, 20, and 28 of age, respectively, with a linear decrease (P<0.05). Postnatal changes in FSR were negatively correlated (P<0.05, r=−0.41) with serum GLP-2 levels. Postnatal changes in cardiac FSR were positively correlated (P<0.05) with the plasma concentrations of Asn, citrulline, His, Leu, ornithine, Ser, taurine, Tyr and Val (r=0.33–0.57) but negatively correlated (P<0.05) with Glu and Gly (r=−0.41 or −0.36). These results indicate dramatic postnatal decreases in cardiac muscle FSR from birth to the post-weaning transition in fed pigs, which correlated well with changes in serum GLP-2 and plasma several AA levels.

A Prospective Study of Serum Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-3 in 942 Healthy Infants: Associations with Birth Weight, Gender, Growth Velocity, and Breastfeeding

Many aspects of hormonal regulation and mechanisms of normal infancy growth are poorly understood. The objective of this study was to establish the determinants of serum growth factor levels in infancy and their association with growth. A prospective, longitudinal, population-based birth cohort between 1997-2001 was studied. Study participants were 942 healthy appropriate weight for gestational age (AGA) infants (538 boys and 404 girls) and 49 small for gestational age (SGA) children (29 boys and 20 girls). INTERVENTIONS were anthropometrical measurements (0, 3, 18, and 36 months) and serum samples (3 months). Height, weight, and serum IGF-I and IGF-binding protein-3 (IGFBP-3) were the main outcome measures. IGF-I levels showed no gender difference [boys, 92 ng/ml (confidence interval, 49, 162); girls, 91 ng/ml (47, 149); P = 0.50]. IGFBP-3 levels were significantly higher in females [2174 ng/ml (1295, 3330)] than in males [2103 ng/ml (1266, 3143); P = 0.04]. Infants receiving breast milk had lower IGF-I levels [90 ng/ml (48, 154)] than infants receiving formula [n = 62; 97 ng/ml (58, 165)] or both [n = 123; 94 ng/ml (48, 169); P < 0.001]. IGF-I and IGFBP-3 levels were positively associated with weight gain and height gain from birth to 3 months of age in AGA, but not in SGA, children. SGA children had significantly lower IGF-I [88.0 ng/ml (28, 145); P = 0.05] and IGFBP-3 [1835 ng/ml (1180, 2793); P < 0.001] levels than AGA children. We found a significant, but weak, association between IGF-I and IGFBP-3 levels at 3 months and postnatal growth in AGA, but not SGA, children. Factors other than IGF-I must contribute to the regulation of normal postnatal growth, and these may differ between AGA and SGA children. IGFBP-3, but not IGF-I, showed a gender difference, which may reflect an influence of the postnatal activation of the pituitary-gonadal axis on binding protein levels.

Serum Levels of IGF-I and IGFBP-3 in Patients With Lung Cancer During Chemotherapy

The aim of this study was to assess serum levels of insulin-like growth factors (IGF-I and IGFBP-3) in patients with lung cancer during chemotherapy. The study included 38 patients (33 males and 5 females; mean age 59.8) diagnosed histologically with lung cancer. Twenty-five patients (65%) had non-small cell lung cancer (NSCLC) and 13 patients (35%) had small cell lung cancer (SCLC). Squamous cell carcinoma was established in 30% (11 patients) of all patients with NSCLC, adenocarcinoma in 13% (5 patients), and non-small cell cancer in 36% (9 patients). The control group consisted of 10 healthy volunteers. Peripheral blood samples were taken before and after four cycles of chemotherapy. IGF-I and IGFBP-3 levels were assessed by ELISA method. Serum levels of IGF-I measured before chemotherapy were significantly higher in both NSCLC and SCLC groups in comparison with controls. No significant differences were observed in serum IGF-I levels before and after four cycles of chemotherapy. The levels were still high after chemotherapy in patients with NSCLC and SCLC. Serum levels of IGFBP-3 were markedly lower in patients with NSCLC both before and after treatment compared to controls. No significant differences were found in patients with NSCLC before and after cytoreduction treatment. Prior to treatment, serum IGFBP-3 levels were significantly lower in patients with SCLC in comparison with controls. After cytoreduction treatment, the levels were decreased when compared to controls but without statistical significance. In conclusion, both before and after chemotherapy serum levels of IGF-I were significantly higher, whereas IGFBP-3 levels were lower in patients with NSCLC and SCLC compared to controls. Chemotherapy had no influence on the serum levels of IGF-I and IGFBP-3. Neither a histological type of NSCLC nor clinical staging had any effect on the serum levels of IGF-I and IGFBP-3.

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.

A Pilot Study To Evaluate the Safety, Efficacy and Effects on Liver Function of Granulocyte Colony-Stimulating Factor To Mobilize Hematopoietic Stem Cells in Patients with Liver Cirrhosis.

In animal models hematopoietic stem cells (HSCs) and the hematopoietic cytokine granulocyte colony-stimulating factor (G-CSF) contribute to tissue regeneration after acute or chronic liver damage. In this study, we assessed whether: 1) G-CSF can be safely administered to patients with liver cirrhosis to expand and mobilize HSCs into peripheral blood; 2) G-CSF treatment affects residual liver function. Eighteen patients with a Child-Turcotte-Pugh (CTP) score < 10 and a Mayo Model for End Stage Liver Disease (MELD) score < 20 were considered eligible for the study. Increasing doses of G-CSF were administered subcutaneously for 7 consecutive days to 5 cohorts of 3 patients each, starting from 2.2 μg/kg/daily, until the achievement of the maximum-tolerated dose and/or the successful mobilization of ≥10 CD34+ cells/μl in at least 2/3 patients. G-CSF mobilizing dose was found at 15 μg/kg/day. Four additional patients were treated with the mobilizing G-CSF dose. All of them showed a successful mobilization of HSCs with a median peak value of CD34+ and CD133+ cells of 27.1(±15.5) and 15.2 (±5.1)/μl, respectively. Circulating HSCs were then collected by single volume leukapheresis and a median of 1.4(±0.73)x106 CD34+ HSCs/kg body weight were cryopreserved. G-CSF treatment induced a significant increase of hepatocyte growth factor serum level. When we analyzed stem cell subsets, we found significant mobilization of early hematopoietic (CD34+/CD38−) and endothelial (CD34+/KDR+, CD133+/KDR+) progenitors as well as CD34+/CXCR4+ cells. No severe adverse events were observed at any dosage or during leukapheresis. According to CTP and MELD score, no significant modification of liver function was observed during the treatment period and follow up (median=198 days) in both mobilizing and non-mobilizing patients. Nevertheless, in all treated patients a significant reduction of alpha-fetoprotein values was observed (p<0.001). In conclusion, the administration of G-CSF to patients with liver cirrhosis is safe, feasible and capable of mobilizing HSCs at the dosage of 15 μg/kg/day. Our study represents the first step for evaluating the role of G-CSF and mobilized HSCs to improve liver function in patients with liver cirrhosis.

Enhanced Detection of Hepatocellular Carcinoma

Tumor markers in the early detection of tumors are promising tools that could improve the control and treatment of tumors. While alpha-fetoprotein (AFP) is a commonly used tumor marker in the detection of hepatocellular carcinoma (HCC), its sensitivity and specificity are insufficient to detect HCC in all patient samples. We compared AFP with serum levels of vascular endothelial growth factors (VEGF and VEGF-A), insulin-like growth factor-2 (IGF-II), and the activity of the lysosomal enzyme alpha-L-fucosidase (AFU) in the sensitivity of detection of HCC and cirrhosis in Egyptian patients. The sensitivity of tumor detection using AFP was 68.2%. This level of detection was increased to 88.6% when AFP was evaluated in conjunction with AFU. The combined use of AFP and VEGF increased the sensitivity of detection to 95.5% in patients with HCC. The combination of the three markers yielded 100% detection sensitivity. VEGF-A showed a low specificity (20%), and IGF-II showed extremely low sensitivity (4.5%). We suggest that AFU or VEGF or both be measured with AFP to improve the detection sensitivity of HCC.

Serum levels of growth factors in patients with non-unions: influence of BMP-7

Serum levels of growth factors in patients with non-unions: influence of BMP-7

IGF-1, IGFBP-3, and Nutritional Factors in Young Black and White Men: The CARDIA Male Hormone Study

: Nutritional factors might play a role in regulating serum levels of insulin-like growth factors (IGFs), which are associated with some cancers. We examined the associations of nutritional factors with IGF-1 and IGF binding protein-3 (IGFBP-3). Serum IGF-1 and IGFBP-3 levels and dietary intake were measured in 459 black and 682 white male subjects of the Coronary Artery Risk Development in Young Adults study at the Year 7 (1992-1993) exam. Analysis of covariance and multivariable linear regression were used to assess associations of IGFs with dietary factors by race. IGF-1 was positively associated with magnesium in both black and white men (P = 0.008 and 0.05, respectively). Calcium was positively significantly related to IGF-1 in black men (P = 0.04) and marginally so in white men (P = 0.09). In black men, IGFBP-3 was positively associated with magnesium (P = 0.02), and one serving of milk per day was associated with an 8.23-ng/ml higher IGF-1 concentration (P = 0.05). Tests for interaction, however, revealed no differences between blacks and whites in the associations of nutrients with IGF-1 or IGFBP-3. In conclusion, the associations of dietary factors with serum IGF-1 and IGFBP-3 observed in our study corroborate those from other studies and generally do not differ between black and white men.

Serum hepatocyte growth factor levels predict long-term clinical outcome after percutaneous coronary revascularization

To evaluate, in patients referred for elective percutaneous coronary revascularization (PCR) without heparin pre-treatment, the relationship between baseline serum levels of the angiogenic growth factors, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and clinical outcome. In 488 consecutive patients undergoing elective coronary angioplasty, hsC-reactive protein, HGF, and VEGF levels were measured before heparin administration. The primary endpoint, a composite of death and myocardial infarction, occurred in 44 patients at a median follow-up of 14.9 months. At baseline, VEGF levels were related to C-reactive protein levels and inversely related to age; HGF levels were related to C-reactive protein levels, diabetes, and recent clinical instability. In the univariate analysis, HGF had a significant positive relationship (P=0.003) with the primary endpoint. A similar trend was observed for VEGF (P=0.11). The only three variables significantly associated with the primary endpoint in the multivariable Cox model were HGF (P=0.004), C-reactive protein (P=0.007), and diabetes (P=0.04). Our results demonstrate that in patients, without heparin pre-treatment, referred for PCR, a high serum level of HGF is an independent predictor of clinical events during follow-up and is correlated with other surrogate measures of the activity of atherosclerosis.

Pretreatment vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) serum levels in patients with metastatic non-small cell lung cancer (NSCLC)

In the present study, we investigated the prognostic value of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 serum levels in patients with metastatic non-small cell lung cancer (NSCLC). From September 1999 to June 2001, pretreatment serum levels of VEGF and MMP-9 were analysed in 194 patients of a randomized phase III trial with enzyme-linked immunoassays. Patients with a VEGF serum level higher than the median serum level (10,995 pg/ml) had a significantly shorter overall survival than those with a lower serum level (P=0.04). The MMP-9 serum level did not correlate with survival. In a multivariate Cox regression analysis, only the pretreatment serum level of VEGF, the Karnofsky performance status, and the presence of bone metastases were identified as independent prognostic factors. The pretreatment VEGF serum level was identified as independent prognostic factor in this study and may help to assess individual risk and treatment profiles in patients with metastatic NSCLC.

Serum vascular endothelial growth factor C (VEGF-C) as a specific biomarker for advanced cervical cancer: Relationship to insulin-like growth factor II (IGF-II), IGF binding protein 3 (IGF-BP3) and VEGF-B

An early non-invasive diagnosis of cervical cancer and its metastasis can save lives. We have shown that serum IGF-II levels can be effectively used for a specific early diagnosis of cervical cancer. Here, we shall determine if serum levels of vascular endothelial growth factors B and C (VEGF-A [corrected] VEGF-C) associated with vasculogenic and lymphogenic metastasis may be used for an early diagnosis of advanced metastatic cervical cancer and compare these levels with those of the serum IGF-II and IGF-binding protein 3 (IGF-BP3). (a) Serum levels of IGF-II, IGF-BP3, VEGF-A [corrected] (VEGF(165)) and VEGF-C (ELISA kits) were determined in: 82 controls with normal Pap smears; 29 women with atypical squamous cells of undetermined significance (ASCUS) and normal cervical biopsy; 46 ASCUS and cervical intraepithelial neoplasia (CIN) on biopsy; 8 pre-therapy CIN-I; 23 successfully treated CIN-I; 75 persistent CIN-I; 14 CIN-II/III pre-therapy; 14 successfully treated CIN-II/III; 70 persistent CIN-II/III; 86 pre-therapy cervical cancer; 26 in early grades of cervical cancer; 21 in late grades of cervical cancer; 22 cervical cancer patients in remission; 50 persistent cervical cancer; 18 with ovarian cancer; and 57 with endometrial cancer. (b) Serial serum samples collected over 5 years in 5 women with progressing cervical cancer were also tested. (c) Serum and tissue VEGF-C were enumerated in 20 matched serum (ELISA) and tissue (semi-quantitative immunofluorescent antibody assay) samples from controls, early cervical cancer, late cervical cancer, ovarian cancer and endometrial cancer patients. Student's t test, chi-square analysis and linear regression analysis were used. (a) As anticipated, serum IGF-II levels were elevated as early as ASCUS with CIN on biopsy and continued to be elevated in CIN (all grades; pre-therapy and persistent) and cervical cancer (pre-therapy, early, late and persistent). Serum IGF-II levels were normal in ASCUS with normal biopsy, successfully treated CIN-I, II/III, cervical cancer as well as pre-therapy ovarian and endometrial cancers (therapy efficacy: P < 0.0001 by chi-square analysis). Serum IGF-BP3 showed a significant decrease with advancing disease. Serum VEGF-A [corrected] levels were the highest in pre-therapy, early, advanced and persistent cervical cancer, as well as in ovarian and endometrial cancers. Serum VEGF-C levels, on the other hand, were the highest in late and persistent cervical cancers, but not in ovarian or endometrial cancers. (b) In the 5 women with serial samples, the serum levels of the growth factors showed similar trends. (c) VEGF-C levels in serum and tissue were elevated in cervical cancers especially in advanced grades, while they were normal in serum and tissue from the controls and women with ovarian and endometrial cancers. There was a highly significant positive correlation between VEGF-C and IGF-II and a negative correlation between IGF-BP3 and VEGF-C (P < 0.0001). Serum IGF-II up-regulation is specific to cervical cancer and helps in the early diagnosis of malignant proliferation, while serum VEGF-C up-regulation appears to be a unique marker for an early diagnosis of cervical cancer metastasis. VEGF-C and IGF-II systems appear to be interrelated in cervical cancer, contributing to the early malignant cell proliferation and lympho-vascular metastasis. Serum IGF-BP3 and VEGF-A [corrected] appear to be common markers for all gynecological cancers.

TGF-β1 as a marker of delayed fracture healing

Mitogens of the TGF-β superfamily have been shown to be crucial local and systemic regulatory molecules involved in fracture healing. However, there exists only little information about systemic regulation of bone regeneration by growth factors and no reports comparing serum levels of bone growth factors between normal and failed fracture healing have been published so far. We hypothesized that quality of fracture healing might be reflected by systemic alterations of key regulatory growth factors involved in bone formation and remodeling. Therefore, the aim of this study was to evaluate possible differences in serum levels of BMP-2, BMP-4, and TGF-β1 in patients with normal and delayed fracture healing. 103 patients with diaphyseal fractures of long bones were recruited prospectively. Peripheral blood samples were collected over a period of 6 months following a standardized time schedule. At the end of the individual investigation period, growth factor serum levels were measured using commercially available enzyme immunoassays. For the elimination of disturbing influences, patients in both groups were matched by gender, age, fracture type, and localization as well as applied technique of osteosynthesis. During a study period of 1 year, 10 patients with an atrophic type of delayed union could be retrieved and matched to 10 patients with normal fracture healing. The diagnosis of delayed union was assumed in case of failed consolidation 4 months after trauma. We found an increase of TGF-β1 serum levels up to 2 weeks after fracture in both groups with a following return to the reference value within 6 weeks after trauma. However, decline of serum concentration occurred earlier in patients with delayed fracture healing. At 4 weeks after trauma, serum levels of TGF-β1 were significantly lower in patients of the delayed union group. Serum levels of BMP-2 and BMP-4 were below detection level in all patients, respectively. These findings support the critical role of TGF-β1 in fracture healing. Events during the consolidation phase seem to be dependent on sufficient availability of TGF-β1.

Changes in Serum Levels of Growth Factors in Healthy Individuals After Living Related Liver Donation

Introduction To obtain better insight into the kinetics of hepatic growth factors following partial hepatectomy for living related liver donation, we investigated the postoperative changes in serum levels of hepatocyte growth factor (HGF), epidermal growth factor (EGF), vascular epidermal growth factor (VEGF), and transforming growth factor-alpha (TGF-alpha). Patients and Methods Eighteen healthy donors undergoing right hepatectomy for living related donation were enrolled in this study. Serum levels of HGF, EGF, VEGF, and TGF-alpha were measured using enzyme-linked immunosorbent assay kits before surgery, at 2 hours after resection, and daily during 5 days postoperatively. Results Mean preoperative HGF serum levels in healthy adults were 778 ± 64 pg/mL. Within 2 hours after operation, they significantly increased to 9608 ± 3111 pg/mL afterward decreasing to 2726 ± 241 at day 1 and 2283 ± 250 pg/mL at day 2. Hereafter HGF serum levels stabilized at increased levels until day 5 (2109 ± 138, 2047 ± 219, 2283 ± 336 pg/mL, respectively). At all time points, the differences between pre- and postoperative HGF levels were significant ( P < .01). In contrast, VEGF and EGF serum levels showed no significant differences between pre- and postoperative levels at all time points. TGF-alpha was not detected using a commercially available test with a detection limit of 10 ng/mL, suggesting only low TGF-alpha serum levels following liver resection. Conclusion Significantly increased HGF serum levels after hepatectomy demonstrate its crucial role among the other investigated growth factors in regeneration of the remnant liver tissue during the early period after the operation.

Circulating and synovial levels of IGF-I, cytokines, physical function and anthropometry differ in women awaiting total knee arthroplasty when compared to men

Purpose: Determine if gender differences in osteoarthritis relate to cytokine and growth factor levels. Methods: Cross-sectional comparison of serum and synovial concentrations of cytokines (IL-1αβ, TNF-α, IL-6), growth factors (IGF-I, TGF-β, IRAP), physical performance and perceived function in total knee arthroplasty candidates (TKAC) ( n = 17) and healthy controls ( n = 21) was done. Results: Serum IGF-I values were reduced in female (TKAC 137.6 ± 7.2; Controls 160.2 ± 26.2) but not male TKAC (TKAC 182.6 ± 18.4; Controls 184.0 ± 18.4) ( p < 0.05).). Serum and synovial levels of cytokines and growth factors did not differ significantly by group or gender. Physical performance testing (SPW, TUG) revealed significant group and gender differences ( p = 0.001) with women demonstrating greater functional impairment. Discussion: A systemic, not local component to OA pathophysiology may exist for female TKAC. Male TKAC were less impaired, and their IGF-I levels differ little from Control values.

Angiogenic Cytokines: Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor Levels in Serum of Children with Hematopoietic Malignancies and Solid Tumors.

Angiogenesis is a process of blood vessel formation from the preexisting capillaries. It plays an essential role of growth and development of cancer. The most important angiogenic stimulators are Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF). The aim of the study was to evaluate the serum levels of VEGF and bFGF in children with solid tumors, hematological malignancies and in healthy controls. Patients: 110 children (33 with solid tumors and 77 with hematological malignancies, including 46 with acute lymphoblastic leukemia and 17 with acute myeloblastic leukemia) (56 male and 54 female) aged 2–18 years (median 8.5 years) and 70 healthy controls (31 male and 39 female) aged 3–18 years (median 13 years). For the quantitative determination the Quantikine VEGF and bFGF immunoassay, a solid-phase enzyme-linked immunosorbent assay method was used. Elevated VEGF and bFGF were defined as being higher than the 95 percentile value in control group. Results: At the time of diagnosis the range of VEGF serum levels in all cancer patiens was 0–2691.3 pg/ml, and in remission 6.08–967.67 pg/ml; while the range of bFGF at diagnosis was 0–64.48 pg/ml, and in remission 0–32.52 pg/ml. In all children with cancer, serum levels of VEGF and bFGF were significantly more often elevated than in healthy controls (p<0.004; p<0.0005). At diagnosis, almost 12% patients had simultaneously elevated serum levels of VEGF and bFGF. Among patients with solid tumors at the time of diagnosis, elevated levels of VEGF and bFGF was observed in 42% and 60%, respectively. There were no differences between serum levels of these factors in patients in remission and in control group. In patients with progression, serum levels of VEGF and bFGF were higher, when compared to levels of these factors at diagnosis. The range of serum levels of VEGF in children with solid tumors at the time of diagnosis was 85.96–2691.3 pg/ml (median 365.48 pg/ml), and in remission 6.08–787.16 pg/ml (median 204.1 pg/ml). The median level of VEGF at diagnosis in children with hematopoietic malignancies (range 0–1869.6 pg/ml, median 111.6 pg/ml) was lower than in children with solid tumors (p<0.0005). In children with acute leukemias at diagnosis, serum levels of VEGF were significantly lower than in children with lymphomas (p<0.0003) and in controls (p<0.05). These results suggest that evaluation of serum levels of VEGF and bFGF can be helpful for monitoring activity of cancer, particularly in solid tumors and in the future can be a target of anti-angiogenic therapy.