Serum Basic Fibroblast Growth Factor Research Articles

Serum basic fibroblast growth factor and interleukin-1β predict the effect of first-line chemotherapy in patients with advanced gastric cancer.

The incidence and mortality rates of gastric cancer in China are the second-highest in the world, and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis. To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1β levels for the effect of first-line chemotherapy in patients with advanced gastric cancer. From the gastric cancer patients admitted to our hospital from May 2019 to April 2023, 84 patients were selected and randomly and equally assigned to the experimental or control group. The FLOT group received the FLOT chemotherapy regimen (composed of oxaliplatin + calcium folinate + fluorouracil + paclitaxel), while the SOX group received the SOX chemotherapy regimen (composed of oxaliplatin + tiga capsules). The clinical efficacy, tumor marker levels, adverse reactions, and survival rates of the two groups were compared 7 days after the end of the relevant treatments. The target effective rate of the FLOT group was 54.76%, which was much higher than that of the SOX group (33.33%; P < 0.05). After treatment, both the groups demonstrated lower levels of cancer antigen (CEA), carbohydrate antigen 199 (CA199), and peptide tissue antigen (TPS). For several patients before treatment (P < 0.05). Third and fourth grades. In terms of adverse reactions, the level of white blood cells in both the groups was lower. Moreover, the incidence of hand-foot skin reactions in these two study groups was lower (P < 0.05), while those of peripheral neuritis, vomiting, diarrhea, and abnormal liver function were significant (P < 0.05). No statistically significant difference was noted between the two groups (P < 0.05). The 1-year survival rate was higher in the FLOT group (P < 0.05). The FLOT regimen was effective in reducing the serum CEA, CA199, and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability, making it worthy of clinical promotion and application.

Changes in serum basic fibroblast growth factor concentration following intracordal injection.

Although many studies have reported improvements in voice outcomes with intracordal trafermin injection, there is a lack of data documenting its changes in serum basic fibroblast growth factor (bFGF) blood concentration. This study examined whether serum bFGF concentrations change after intracordal trafermin injection. This retrospective study was conducted at Tokyo Voice Center. We investigated serum bFGF concentrations before and after injection in 40 patients who underwent intracordal trafermin injection. There were 26 males and 14 females, with an age ranging from 13 to 88 years (average 53.25 years). They were diagnosed with paralysis (15 patients), atrophy (15 patients), sulcus (8 patients), and others (2 patients: scar and functional), presenting with severe hoarseness that interfered with daily life. The mean pre- and post-injective serum bFGF concentration of the 40 patients was 6.689 and 4.658 pg/mL, respectively. The difference in mean serum bFGF concentration between pre- and post-injective was -2.031 pg/mL. The Pearson correlation coefficient was calculated to evaluate the correlation between dosage of trafermin and post-injective serum bFGF concentration, and a moderate correlation was found at r = 0.52. Generalized linear model regression analysis was performed for the purpose of adjusting for confounding among variables. The only variable that showed a statistically predominant association with post-injective serum bFGF concentrations was the dosage of trafermin, with an estimated regression coefficient of 0.048. In this study, the dosage of trafermin we injected and post-injective serum bFGF concentrations were dose-dependent but the amount of changes in the serum bFGF concentration was negligible within the physiological range. Therefore, as with subcutaneous and wound administration, intracordal trafermin injections may be safe. Level IV.

Efficacy of lenvatinib combined with sequential transarterial chemoembolization for primary hepatocellular carcinoma and the effects on serum basic fibroblast growth factor and vascular endothelial growth factor.

Objective: The aim of this research was to investigate the therapeutic efficacy of lenvatinib combined with sequential transarterial chemoembolization (TACE) on primary hepatocellular carcinoma (HCC) and the effects on serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Method: A total of 104 patients with primary HCC, admitted to People's Hospital of Leshan from April 2018 to January 2021, were selected as the study subjects and were divided into the TACE-LEN group (n = 53) who were treated with lenvatinib combined with sequential TACE and the TACE group (n = 51) who were treated with TACE alone, according to the appropriate treatment modalities. The clinical efficacy 8weeks after treatment; the serum levels of total bilirubin, conjugated bilirubin, and alanine aminotransferase (ALT); the prothrombin time (PT); the indocyanine green retention rate at 15min (ICGR15); and the serum bFGF and VEGF levels before treatment and at 8weeks after treatment were compared between the two groups. The incidence of adverse events and the survival rates at 18 months were also recorded for both groups. COX regression analysis was used to analyze the risk factors affecting the survival of patients. Results: Eight weeks after treatment, the objective response rate was higher in the TACE-LEN group than in the TACE group (77.36% vs. 56.36%, p < 0.05), but there were no statistically significant differences in the bilirubin and ALT levels, the PT, and the ICGR15 between the two groups (p > 0.05). The serum bFGF and VEGF levels post-therapeutic were lower in the TACE-LEN group than in the TACE group (p < 0.05). The differences in the incidence of postoperative adverse events and the survival rate within 6months were not statistically significant between the two groups (p > 0.05). In addition, the survival rates within 12 and 18months after treatment were higher in the TACE-LEN group than in the TACE group than in the TACE group (81.1% vs. 64.7%, 69.8% vs. 49.1%, p < 0.05). ICG-R15 and treatment regimen are risk factors for survival. Conclusion: The worse the liver reserve is, the worse the prognosis is. The combination of TACE and lenvatinib showed better efficacy and longer survival than TACE monotherapy for HCC patients and reduced the levels of bFGF and VEGF.

Elevated Angiogenic Factor Levels After Transarterial Radioembolization for Colorectal Cancer Liver Metastases May Predict a Poor Prognosis.

Objectives:To analyze the change in circulating angiogenic factor levels after transarterial radioembolization (TARE) for colorectal cancer liver metastases (CRCLMs) and its prognostic significanceMethods:Blood samples immediately before TARE and on 1 day, 1 week and 6 weeks after were collected for angiogenic factor analysis in 23 patients.Results:Patients with elevated serum basic fibroblast growth factor and platelet-derived growth factor levels in the 1st week and vascular endothelial growth factor (VEGF) levels in the 6th week after TARE had significantly shorter median overall survival (OS) times.Conclusion:Some early increases in serum angiogenic factor levels and in serum VEGF in the 6th week after TARE for CRCLMs are related to short OS and progression-free survival.

Correlation of CT Perfusion Parameters and Vascular Endothelial Growth Factor (VEGF) and Basic Fibroblast Growth Factor (BFGF) in Patients with Primary Liver Cancer.

Objective To investigate the correlation of CT perfusion-related parameters with serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (BFGF) in patients with primary liver cancer. Methods A total of 100 patients with primary liver cancer who were treated in our hospital from June 2019 to June 2021 were selected as the observation group, and 90 patients with benign liver lesions during the same period were selected as the control group. The CT perfusion-related parameters (perfusion volume and perfusion index) and serum VEGF and BFGF levels were compared between the two groups. Pearson correlation was used to analyze the correlation between CT perfusion-related parameters and serum VEGF and BFGF levels. Results Compared to the control group, significantly higher HAP and lower HPP and TLP were observed in the observation group. The perfusion volume indexes of patients with different stages of liver cancer in the observation group were statistically different (P < 0.05). Compared to the control group, the observation group witnessed significantly higher HAPI and lower HPPI. There were statistically significant differences in the perfusion index of patients with different stages of primary liver cancer in the observation group (P < 0.05). The serum VEGF and BFGF levels in the observation group were significantly higher than those in the control group, and the serum VEGF and BFGF levels in patients with different stages of primary liver cancer in the observation group were statistically different (P < 0.05). Pearson correlation analysis showed that HAP and HAPI were positively correlated with VEGF and BFGF (r = 0.986, P ≤ 0.001; r = 0.983, P ≤ 0.001), and HPP, TLP, and HPPI were negatively correlated with VEGF and BFGF (r = −0.992, P ≤ 0.001; r = -0.993, P ≤ 0.001; r = −0.995, P ≤ 0.001). Conclusion CT perfusion-related parameters and serum VEGF and BFGF levels in patients with primary liver cancer are abnormally expressed, and there is a strong correlation between the two, which might aid clinical diagnosis and treatment.

Role of basic fibroblast growth factor in human immunodeficiency virus associated pre-eclampsia.

Cell signaling is vital to ensure successful trophoblast invasion. This study assessed the level of serum basic fibroblast growth factor (FGF-2) in human immunodeficiency virus (HIV) associated pre-eclampsia (PE). Using a Bio-plex Multiplex Immunoassay, FGF-2 (pg/mL) was analyzed in blood sera collected from 80 pregnant women attending a large regional hospital in Durban, South Africa. Study groups consisted of normotensive and pre-eclamptic pregnant women stratified according to their HIV status. Data analysis was performed using graphpad prism statistics software, version 5.00. In this study, we report a significant decrease of FGF-2 serum level in pre-eclamptic compared to normotensive pregnant women groups (25.38 ± 6.69 pg/mL vs 61.79 ± 11.25 pg/mL), irrespective of their HIV status. Similarly, there was a significant decrease in FGF-2 serum level in HIV positive compared to HIV negative group (33.80 ± 9.62 pg/mL vs 52.15 ± 9.49 pg/mL), irrespective of their pregnancy type. This study demonstrates a downregulation of serum FGF-2 expression in pre-eclamptic compared to normotensive pregnant women. This decline may be responsible for the defective trophoblast invasion and/or to PE severity. The decline in FGF-2 expression in HIV infection is probably due to the effect of HIV Tat protein on angiogenesis.

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.

Effects of lumbar plexus-sciatic nerve block combined with sevoflurane on cognitive function in elderly patients after hip arthroplasty: study protocol for a prospective, single-center, open-label, randomized, controlled clinical trial

Background: Elderly patients often suffer from postoperative cognitive dysfunction after total hip arthroplasty, but the precise mechanism remains unclear. Sevoflurane regulates the concentration of basic fibroblast growth factor in the brain, but it is not known whether sevoflurane can decrease cognitive dysfunction after hip arthroplasty. We hypothesized that lumbar plexus-sciatic nerve block combined with sevoflurane could reduce the incidence of cognitive dysfunction in elderly patients after hip arthroplasty. Methods/Design: We conducted a prospective, single-center, open-label, randomized, controlled clinical trial at the Affiliated Hospital, Qinghai University, China. Seventy elderly patients undergoing unilateral total hip arthroplasty were randomized into two groups. All patients underwent endotracheal intubation and mechanical ventilation. In the experimental group, a lumbar plexus-sciatic nerve block was performed and general anesthesia was maintained with sevoflurane. In the control group, general anesthesia was maintained with intravenous propofol. Outcomes were measured preoperatively and on the first and third postoperative days. The primary outcome measure was the Mini-Mental State Examination, and the secondary outcomes were the Montreal Cognitive Assessment, serum basic fibroblast growth factor concentration, intraoperative blood loss, and operation time. The other outcome was the incidence of intraoperative and postoperative adverse events. Discussion: This trial examined whether lumbar plexus-sciatic nerve block combined with sevoflurane reduced the incidence of cognitive dysfunction in elderly patients after hip arthroplasty, documented the changes in serum basic fibroblast growth factor concentration, and further explored the therapeutic mechanism of sevoflurane. Trial registration: ClinicalTrials.gov identifier: NCT03162861. Ethics: The study protocol has been approved by the Ethics Committee of Affiliated Hospital of Qinghai University of China. All protocols will be in accordance with Declaration of Helsinki, formulated by the World Medical Association. Informed consent: Written informed consent was provided by participants prior to enrollment in the trial.

Clinical significance of fibroblast growth factor (FGF) expression in colorectal cancer.

In this study, we serologically and pathologically examined the clinical significance of fibroblast growth factor (FGF) expression in patients with colorectal cancer. Serum basic FGF (bFGF) levels in 92 surgical colorectal cancer patients and 31 controls were measured, and the relationship between those levels and clinicopathological factors were examined. Immunohistochemical study was also conducted on specimens from 51 cancer patients, and the association between bFGF staining and serum levels were investigated. An examination of clinicopathological factors revealed significant differences in bFGF levels between stage 0-IIIb and stage IV cancers (P = 0.013). Lymphatic invasion was one factor that differed significantly. Patients with a tumor 30 mm or smaller had a bFGF level of 7.65 ± 1.11 pg/ml while patients with a tumor 31 mm or larger had a bFGF level of 8.53 ± 3.22 pg/ml; significant differences in these bFGF levels were noted (P < 0.05). Patients with a tumor that had no lymphatic invasion (ly0) had a bFGF level of 7.25 ± 0.66 pg/ml, those with a tumor that had minimal lymphatic invasion (ly1) had a bFGF level of 7.99 ± 1.68 pg/ml, and those with a tumor that had moderate lymphatic invasion (ly2) had a bFGF level of 9.17 ± 4.23 pg/ml. bFGF levels differed significantly for tumors with no/minimal lymphatic invasion (ly0-ly1) and those with moderate lymphatic invasion (ly2) (P < 0.0001). Serological examination of bFGF levels during the proliferation of colorectal cancer revealed that moderate lymphatic invasion can be readily distinguished.

Culture of Pig Induced Pluripotent Stem Cells without Direct Feeder Contact in Serum Free Media

Background: Reprogramming pig somatic cells into induced pluripotent stem cells (iPSCs) have promising applications in basic biology, disease model development and xenotransplantation. In the mouse, embryonic stem cell (ESC) technology has revolutionized the field enabling gene targeting, complex screening strategies and the creation of animals that show unique characteristics of interest. Recent breakthroughs utilizing induced pluripotent stem cell technology in the pig have made it possible to produce pig pluripotent stem cells that resemble germline chimeric competent mouse ESCs. However, an optimal culture system for piPSC expansion has yet to be developed. Most reports have maintained piPSCs in undefined systems that use xenoproducts and feeder layers, which are potential sources of contamination. Methods: In this study, new lines of pig iPSCs (piPSC) were generated from pig fibroblast cells by overexpressing six reprogramming genes: POU5F1, SOX2, NANOG, LIN28, KLF4 and C-MYC. These new lines were tested for their ability to be maintained on a Matrigel substrate in the established mouse 2i+LIF system, the human mTeSR1 system and variations of a feeder conditioned media system. Analysis and identification of piPSCs were performed using immunocytochemistry, flow cytometry and by examining embryoid body formation and differentiation. Results: The newly generated piPSCs showed morphological features, immunoreactivity and reactivation of endogenous pluripotency networks consistent with iPSCs. Similar to cells cultured on feeders, piPSCs maintained under all 7 feeder-free conditions expressed POU5F1 and NANOG, SSEA-1, SSEA-4 and TRA1-81. However, flow cytometry demonstrated that piPSCs cultured in feeder conditioned media with KnockOut Serum Replacement and basic fibroblast growth factor (FGF2) showed significantly higher levels of SSEA1 and SSEA4 expression than cells cultured in a 2i+LIF or mTeSR1 system. Conclusion: These findings demonstrate that piPSCs can be maintained in defined systems without serum and direct feeder contact, increasing their potential use in both agricultural and biomedical fields.

A phase 1 open‐label trial shows that smad7 antisense oligonucleotide (GED0301) does not increase the risk of small bowel strictures in Crohn's disease

In Crohn's disease (CD), knockdown of Smad7, an inhibitor of Transforming Growth Factor (TGF)-β1 activity, with a specific antisense oligonucleotide (GED0301) seems to be safe and tolerable and associates with TGF-β1-mediated suppression of inflammatory pathways. Since TGF-β1 has pro-fibrogenic effects in many organs, we evaluated whether GED0301 treatment associates with the formation of small bowel strictures. Fifteen patients with active, inflammatory CD, receiving oral GED0301 once daily for 7 days, were monitored for the formation of small bowel strictures by Small Intestine Contrast Ultrasonography (SICUS). Serum basic fibroblast growth factor (bFGF) and human chitinase 3-like 1 (also known as YKL-40), two markers of CD-related intestinal strictures, and matrix metalloproteinases (MMP) and tissue inhibitor 1 of MMPs (TIMP1) were analysed at day 0 and day 180 by ELISA. Crohn's disease activity index (CDAI) changes were also monitored. Fourteen patients completed the 6-month study; the remaining underwent intestinal resection for a severe relapse not responsive to medical treatment. No patient developed small bowel stricture and none experienced obstructive symptoms during the study period. GED0301 treatment induced no significant change in the circulating levels of bFGF, YKL-40, MMPs and TIMP1. Seven of 12 patients who reached clinical remission following GED0301 treatment maintained a CDAI < 150 at day 180. Short-term treatment of patients with Crohn's disease using GED0301 is not associated with the development of small bowel stricture, thus reinforcing the concept that this drug is safe at least at early time points.

Heparan Sulfate Chains of Syndecan-1 Regulate Ectodomain Shedding

Matrix metalloproteinases release intact syndecan-1 ectodomains from the cell surface giving rise to a soluble, shed form of the proteoglycan. Although it is known that shed syndecan-1 controls diverse pathophysiological responses in cancer, wound healing, inflammation, infection, and immunity, the mechanisms regulating shedding remain unclear. We have discovered that the heparan sulfate chains present on syndecan core proteins suppress shedding of the proteoglycan. Syndecan shedding is dramatically enhanced when the heparan sulfate chains are enzymatically degraded or absent from the core protein. Exogenous heparan sulfate or heparin does not inhibit shedding, indicating that heparan sulfate must be attached to the core protein to suppress shedding. Regulation of shedding by heparan sulfate occurs in multiple cell types, for both syndecan-1 and syndecan-4 and in murine and human syndecans. Mechanistically, the loss of heparan sulfate enhances the susceptibility of the core protein to proteolytic cleavage by matrix metalloproteinases. Enhanced shedding of syndecan-1 following loss of heparan sulfate is accompanied by a dramatic increase in core protein synthesis. This suggests that in response to an increase in the rate of shedding, cells attempt to maintain a significant level of syndecan-1 on the cell surface. Together these data indicate that the amount of heparan sulfate present on syndecan core proteins regulates both the rate of syndecan shedding and core protein synthesis. These findings assign new functions to heparan sulfate chains, thereby broadening our understanding of their physiological importance and implying that therapeutic inhibition of heparan sulfate degradation could impact the progression of some diseases.

Diagnostic value of serum basic Fibroblast Growth Factor in gastric ulcers patients for assessment of wound severity

Diagnostic value of serum basic Fibroblast Growth Factor in gastric ulcers patients for assessment of wound severity

The role of serum basic fibroblast growth factor, estradiol and urine basic fibroblast growth factor in differentiating infantile haemangiomas from vascular malformations

To investigate the role of serum basic fibroblast growth factor (bFGF), estradiol (E2) and urine bFGF in differentiating infantile haemangiomas from vascular malformations. Between October 2007 and January 2009, 97 patients with haemangiomas and 25 patients with vascular malformations who had not been treated previously were included in this prospective study. Forty-eight patients with cleft lip and/or palate were selected as controls. The age of all subjects ranged from 1 to 30 months. The serum and urine levels of bFGF were determined by enzyme-linked immunosorbent assay (ELISA). The serum levels of E2 were examined via radioimmunoassay. All data were analysed with SPSS 11.5 software package. The concentration of serum and urine bFGF was significantly different among the three groups (haemangiomas, vascular malformations and controls) (P = 0.027, P = 0.001). Significantly different urine bFGF levels were found in patients with proliferating and involuting haemangiomas (P = 0.04). The serum E2 levels were significantly higher in patients with haemangiomas than vascular malformations (P = 0.001) and controls (P = 0.001). Serum bFGF and E2 as well as urine bFGF can be used to supplement the clinical diagnosis of congenital vascular anomalies. Urine bFGF combined with serum E2 may be the most potential markers for diagnosing haemangiomas and determining the proliferating stage of haemangiomas.

Phase II Study of Concomitant Thalidomide During Radiotherapy for Hepatocellular Carcinoma

Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients. A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samples were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only. No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 ± 48.9 vs. 148 ± 6.2 days, p = .15), or median overall survival (258 ± 45.6 vs. 241 ± 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-α levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1 month after RT completion was a significant predictor of the overall survival of HCC patients receiving RT. Despite the acceptable toxicity, thalidomide provided no additional benefit for HCC patients undergoing RT.

Serum YKL‐40 and bone marrow angiogenesis in multiple myeloma

Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayDear Sir,In a recently published study, Saidi et al. showed that elevatedlevels of CHI3L1 mRNA, encoding the secreted glycoproteinYKL-40, are associated with poor survival in glioblastoma,probably by promoting angiogenesis.

Thalidomide in advanced hepatocellular carcinoma as antiangiogenic treatment approach: a phase I/II trial

The high vascularity of hepatocellular carcinoma (HCC) seems to be a potential therapeutic target. We evaluated the efficacy, toxicity, and histologic response to thalidomide in advanced HCC in a single center phase I/II pilot trial. Between September 2000 and August 2004 patients with HCC uneligible for any established therapy were enrolled in the study. The initial thalidomide dosage of 100 mg/day was escalated in 100 mg steps weekly up to 300 mg/day based on tolerability. Discontinuation and dose reduction were based on toxicity. Tumor biopsies were scheduled to assess tumor microvessel density and serum levels of angiogenic factors, vascular endothelial growth factor, basic fibroblast growth factor, and endostatin were determined. Twenty-eight patients with histologically proven HCC were entered into this study. The median maximum-tolerated dose of thalidomide was 300 mg/day. Most common toxicities were fatigue (75%), dizziness (64%), nausea (43%), and constipation (39%). Two patients had stable disease for 2.6 and 5.4 months, the remaining 26 patients had disease progression. The median overall survival was 5.1 months. Well preserved liver function was associated with longer overall survival on univariate analysis (P=0.0279). The serum concentrations of vascular endothelial growth factor and endostatin increased significantly (P=0.039 and P=0.024, respectively) after 3 months of thalidomide treatment. No clear differences were observed between the serum basic fibroblast growth factor concentrations at study entry and after 3 months (P=0.983). Microvessel density did not decrease significantly during thalidomide therapy (P=0.109). Thalidomide is moderately tolerated and minimally effective in large HCC.

Serum proangiogenic factors in patients with testicular germ cell tumors

16050 Background: Angiogenesis has an established role in the initiation and maintenance of carcinogenesis, as well as a certain role in the establishment of metastatic foci. The role of angiogenesis in testicular germ cell tumors, although obvious, is not fully elucidated. The present study aims to clarify the role of serum proangiogenic factors in patients with testicular germ cell tumors. Methods: We measured serum basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), platelet derived growth factor BB (PDGF-BB) and angiopoietin-2 (Ang-2), using solid phase Elisa in 50 patients (mean age 32,3±9,1 years) with testicular cancer who underwent chemotherapy and in 16 healthy male, age-matched (mean age 31,8±7,12 years) controls. Three serum samples were obtained from patients with testicular cancer: prior to chemotherapy (baseline), before cycle 3, and 9–14 months after the completion of chemotherapy. One serum sample was obtained from controls. Informed consent was taken before the obtainment of the samples. Results: Baseline mean serum bFGF, VEGF, PDGF-BB, and Ang-2 were 666,5 ±550pg/ml, 228,3±181pg/ml, 10623,8pg/ml, 4089,82±3312pg/ml in patients and 1153,6±967pg/ml, 158,9±137pg/ml, 8726,1±4318pg/ml, 2647,2±1186pg/ml in controls (p=0,1, p=0,8, p=0,3 and p=0,013). Mean serum values 1 year after the completion of chemotherapy were 310,8±298pg/ml, 139±127pg/ml, 7500±3726pg/ml and 6275±5600pg/ml (p=0,044, p=0,198, p<0,001, p=0,008). As we can see, there was a trend toward normalization of proangiogenic factors values, especially for PDGF-BB and Ang-2, and there was a difference between patients and controls for Ang-2. Ang-2 was also statistically significant different between good (n=8) and intermediate-bad prognostic groups (n=42) (mean values 3413±2100 and 5291±3200, p=0,03). Conclusions: These results support the notion about the role of proangiogenic factors in germ cell carcinogenesis. Especially angiopoietin-2 seems to play a significant role, as it was the only factor with statistically significant difference between patients and controls and the only factor with difference between the various prognostic groups. Further study of angiopoietin-2 and its role in germ cell tumors is warranted. No significant financial relationships to disclose.

Pharmacokinetic and pharmacodynamic study of intratumoral injection of an adenovirus encoding endostatin in patients with advanced tumors

Angiogenesis plays a pivotal role in tumor growth, tissue invasion and metastasis. Endostatin is an angiogenesis inhibitor and has been shown to reduce tumor growth in animal models. However, therapy with recombinant endostatin protein was hampered by its short half-life and very-low yield of bioactive protein. We performed a phase I dose-escalation clinical trial using intratumoral injection of an adenovirus containing human endostatin gene (Ad-rhE; E10A; 10(10)-10(12) virus particles (vp)) in 15 patients with advanced solid tumors. We observed intratumoral injections of E10A without dose-limiting toxicity. Most frequently reported E10A-related adverse events were transient fever and local response. Distribution studies revealed that the vector was detected in the blood, throat and injection site, but rarely in the urine and stool. An increased endostatin expression was detected using enzyme immunoassay in serum in 13 of 14 treated patients throughout the period of treatment despite the presence of neutralizing antiadenovirus antibody. Median serum basic fibroblast growth factor levels decreased from 32.4 pg ml(-1) at baseline to 24.9 pg ml(-1) after 28 days of first treatment. Thus, direct intratumoral injection of up to 10(12) vp of E10A to patients is well tolerated and further studies are necessary to define and increase clinical efficacy.

Elevated vascular endothelial growth factor levels are associated with aortopulmonary collateral vessels in patients before and after the Fontan procedure

Aortopulmonary collaterals (APCs) are frequently observed before and after the Fontan procedure. However, the mechanism of the development of APCs is unknown. We hypothesized that one or several antiangiogenic and/or angiogenic growth factors might play a role in the development of APCs. Eighty-five patients were enrolled and divided into 3 groups (Fontan group: 30 patients after the Fontan procedure, cyanotic group: 29 patients with cyanotic heart disease, and control group: 26 patients with cyanotic heart disease after biventricular repair). We measured basic fibroblast growth factor, vascular endothelial growth factor (VEGF), hepatocyte growth factor, and endostatin at catheterization. Angiographic evaluation for the presence of APCs using a 4-point scale (grade 1: absent APCs, > or = grade 2: significantly present APCs) was performed, and the relation of the serum levels of these factors to the presence of APCs was assessed. The grade of APCs significantly increased in the Fontan group, but it decreased in the control group. The serum VEGF levels were higher in the Fontan group (280 +/- 174 pg/mL) and the cyanotic group (302 +/- 245 pg/mL) than in the control group (111 +/- 91 pg/mL) (P = .0004), and they were higher in patients with APCs (383 +/- 204 pg/mL) than in those without APCs (115 +/- 65 pg/mL) (P < .0001). There was no significant difference in the serum basic fibroblast growth factor, hepatocyte growth factor, and endostatin levels between the 3 groups. Aortopulmonary collaterals increase after the Fontan procedure. Serum VEGF levels are associated with the presence of APCs. Vascular endothelial growth factor may play a role in the development of APCs in patients with cyanotic heart disease and after the Fontan procedure.