Serum Levels Of Placental Growth Factor Research Articles

Chronic kidney disease may be differentially diagnosed from preeclampsia by serum biomarkers

Preeclampsia, affecting 5-8% of pregnancies, is the main cause of fetal-maternal mortality and morbidity. The differential diagnosis with chronic kidney disease (CKD) is a challenge owing to the overlapping clinical features. No biomarker has been found to discriminate between the two conditions. Here, we tested whether maternal serum levels of placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1), markers of preeclampsia, could be used to discriminate between 34 patients with preeclampsia, 23 patients with CKD during pregnancy, and 38 healthy pregnant women. Serum levels of PlGF and sFlt-1 were determined during the third trimester by commercially available immunoassays. In preeclampsia, sFlt-1 levels were significantly increased in comparison with that in CKD and in the control women. Serum levels of PlGF in preeclampsia were significantly decreased relative to both controls and patients with CKD. The sFlt-1 to PlGF ratio was significantly increased in preeclampsia (median 436) compared with controls (median 9.4) and CKD (median 4.0). No differences were found between controls and patients with CKD. Thus, our study suggests that it is possible to discriminate between preeclampsia and CKD during pregnancy by determining maternal serum levels of sFlt-1 and PlGF and their ratio.

Increased expression of placental growth factor in high-grade endometrial carcinoma

Placental growth factor (PlGF), a homolog of vascular endothelial growth factor (VEGF), exerts pleiotropic functions in cancer by affecting tumor cells as well as endothelial and inflammatory cells. Moreover, PlGF expression correlates with tumor stage, recurrence, metastasis and patient outcome in different types of cancer. Recently, administration of anti-PlGF therapy reduced tumor growth and metastasis in preclinical tumor models. In the present study, we evaluated the diagnostic and prognostic value of systemic and local expression of PlGF in primary endometrial carcinomas. PlGF levels in tumor lysates (n=128) and serum (n=88) of patients with primary endometrial cancer were determined using ELISA. PlGF mRNA expression in endometrial carcinoma tissues was quantified by quantitative qRT-PCR. Results were compared to endometrial cancer stage and grade. Systemic PlGF levels were not altered in patients with endometrial cancer (FIGO stage I-II-III) as compared to healthy controls. Only in FIGO stage IV patients, serum PlGF levels were slightly increased. Local PlGF mRNA and protein expression in endometrial tumors progressively increased with tumor grade. In endometrioid carcinomas, PlGF mRNA expression was significantly increased in endometrioid grade 3 tumors as compared to normal endometrial tissue. PlGF protein expression was significantly increased in endometrioid grade 2 and 3 carcinomas and in serous carcinomas as compared to normal endometrial tissue. Our study showed that systemic/serum PlGF levels cannot be used as a diagnostic or prognostic marker in endometrial cancer. However, the increased local expression of PlGF, primarily in high-grade carcinomas, underscores the possibility for preclinical assessment of anti-PlGF therapy in endometrial cancer.

PP122. Lack of correlation between placental weight and circulating soluble fms-like tyrosine kinase-1 and placental growth factor suggests trophoblastic activity as a major contributor to the serum pool

Serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are altered in preeclampsia and fetal growth restriction. Whether the alterations result from mere variation in trophoblastic mass or trophoblastic activity in these diseases is still elusive. Using placental weight as a surrogate for trophoblastic mass, we explored the relationship between placental weight at delivery and serum levels of sFlt-1 and PlGF at various gestational ages in normotensive pregnant Thai women. One hundred and forty two serum samples from healthy, normotensive, singleton Thai pregnant women were prospectively collected from 6 gestational age intervals; 10-14, 15-19, 20-24, 25-29, 30-34, and 35-40weeks'. Analysis for the levels of sFlt-1 and PlGF was made from fresh specimens, using a commercially available automated system. Placental weight at delivery was followed in participants who remained unaffected with preeclampsia or fetal growth restriction until the time of delivery. Statistical analyses were achieved from 140 participants. Quartiles for these markers were calculated for each gestational age interval. Serum sFlt-1 levels continuously increased through the pregnancy. Serum PlGF levels reached its peak levels at menstrual period of 25-29weeks', and then declined. Serum sFlt-1/PlGF ratios were consistently lower than that of the European population throughout the pregnancy. No significant correlation is found between placental weight at delivery, and serum levels of either sFlt-1 or PlGF at any gestational age interval. Ethnic variation of serum angiogenic markers is shown in this study. Lack of correlation between placental weight and serum angiogenic markers in normotensive individuals suggest that trophoblastic activity, and not number of the trophoblast, contribute to the alterations in circulating pool. This may facilitate a better understanding for its potential clinical applications of these biomarkers for other placental related diseases.

Prognostic relevance of circulating PIGF levels in patients with neuroendocrine tumors.

4128 Background: Placental growth factor (PlGF), a VEGF homolog implicated in tumor angiogenesis and adaptation to antiangiogenic therapy, is emerging as candidate target in malignancies. As antiangiogenic treatments are introduced in the management of neuroendocrine tumors (NETs), we addressed the expression and function of PlGF in NETs. Methods: Serum levels of PlGF were determined in two independent cohorts of NET patients collected retrospectively and prospectively (n=87 and n=84) using Roche Elecsys and correlated with clinical data. Expression of PlGF in tumors was evaluated by immunohistochemistry. PlGF effects on proliferation and migration were examined in vitro using NET cell lines. Results: Circulating and tumoral PlGF were found elevated in NET patients as compared to control sera and pancreatic tissues in a retrospective analysis restricted to patients with pancreatic NETs (pNETs). De novo expression of PlGF occurred primarily in the tumor stroma, suggesting paracrine stimulatory circuits. Indeed, PlGF enhanced proliferation and migration of NET cells, and elevated circulating PlGF levels correlated with advanced tumor grading, suggesting that PlGF supported a more aggressive phenotype. In line with this notion, circulating PlGF levels above median predicted reduced tumor related survival in pNET patients (p=0.012). Furthermore, pathologic PlGF levels were associated with poor prognosis within the subgroup of grade 2 tumors. Subsequent prospective PlGF determinations confirmed and extended our observation of elevated PlGF levels for both, pNETs (n=32, p<0.001) and midgut NETs (n=58, p<0.001). Since median follow up was too short to determine survival, time to progression (TTP) was analyzed instead. Most pNETs were progressive at the time of sample collection, precluding an informative evaluation of TTP in this subgroup. However, PlGF levels above median were correlated with shorter TTP in midgut NETs (p=0.0091; TTP 27 months versus undefined, HR 3.802). Conclusions: These data assign to PlGF a novel function in the pathobiology of NETs and propose PlGF as a prognostic parameter in patients with NETs.

Serum Concentrations of Soluble Flt-1 Are Decreased among Women with a Viable Fetus and No Symptoms of Miscarriage Destined for Pregnancy Loss

Miscarriage is the most common complication of pregnancy. Pre-clinical miscarriage has an estimated incidence of 30%, whilst clinical miscarriage has an incidence of 12-15%. Two thirds of pregnancies lost to miscarriage are believed to be attributable to defective placentation, thus a number of studies have sought to identify markers of defective placentation that could be used as clinical biomarkers of miscarriage. Decreased soluble FMS-like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF), and soluble endoglin (sEng) in the maternal circulation during the first trimester have recently been proposed as potential markers of pregnancy loss. However, in these studies clinical samples were only obtained once women had presented with symptoms of miscarriage. In this study we prospectively screened serum samples collected from asymptomatic women with a viable fetus. We assessed maternal serum levels of sFlt1, PlGF and sEng across the first trimester of normal pregnancy and compared levels between women who continued to a live birth, to those who subsequently miscarried. Both sFlt1 and PlGF significantly (p≤0.05) increased across gestation in normal pregnancy with serum levels rising from 0.65±0.12 ng/ml at 6 weeks to 1.85±0.24 ng/ml at 12 weeks for sFlt1, and 57.2±19.2 pg/ml to 106±22.7 pg/ml for PlGF. sEng remained unchanged throughout the the first trimester. Importantly we detected a significant (35%, p≤0.05) decrease in sFlt1 levels between our control and miscarriage cohort, however there was significant overlap between cases and controls, suggesting serum sFlt1 is unlikely to be useful as a clinical biomarker in asymptomatic women. Nevertheless, our data suggests a dysregulation of angiogenic factors may be involved in the pathophysiology of miscarriage.

Association between placental growth factor levels in early onset preeclampsia with the occurrence of postpartum hemorrhage: A prospective cohort study

ObjectivesTo determine the association between PlGF (placental growth factor) estimation in early second trimester (22–24weeks of gestation), with the occurrence of postpartum hemorrhage in pregnant women with early onset preeclampsia and whether the mode of delivery (cesarean or vaginal) has any association with increased risk of developing postpartum hemorrhage. Study designA prospective cohort study was conducted on 788 pregnant women with singleton pregnancies diagnosed with early onset preeclampsia between March 2009 and June 2011. Maternal serum PlGF level estimation was done between 22 and 24weeks of gestation and a cut-off value of <122pg/ml was determined by receiver operating characteristic (ROC) curve analysis for identifying those at risk of developing postpartum hemorrhage. Association between serum PlGF level <122pg/ml and cesarean deliveries with the risk of developing postpartum hemorrhage was analyzed by logistic regression analysis and Odds ratio, which were computed. The results were considered statistically significant when P-value <0.05. Main outcome measuresProportion of study population developing postpartum hemorrhage. ResultsLogistic regression analysis showed the association of serum PlGF <122pg/ml at 22–24weeks (Odds ratio 8.9516; 95% CI, 5.0728–15.7963) and that of cesarean delivery (Odds ratio 2.4252; 95% CI, 1.4573–4.0360) with the risk of developing postpartum hemorrhage. Both the associations were found to be statistically significant. ConclusionMaternal serum PlGF level <122pg/ml at 22–24weeks of gestation and cesarean delivery are both strongly associated with the risk of developing postpartum hemorrhage in pregnant women with early onset preeclampsia.

Angiogenic biomarkers predict the occurrence of digital ulcers in systemic sclerosis

ObjectiveTo evaluate the possible merit of endothelial markers for the prediction of ischaemic digital ulcers in patients with systemic sclerosis (SSc).MethodsCirculating endothelial progenitor cells (EPC), circulating endothelial cells and serum...

Longitudinal trends in fetoplacental biochemical markers, uterine artery pulsatility index and maternal blood pressure during the first trimester of pregnancy

To assess trends in levels of biochemical markers, uterine artery (UtA) pulsatility index (PI) and maternal blood pressure changes over time and study their relationships in uncomplicated first-trimester pregnancies. The study population comprised 86 women with singleton pregnancies. In each woman, a blood sample was collected at 6-7, 8-9, 10-11 and 12-13 weeks' gestation. At the same visit blood pressure was measured and ultrasound examination was performed to measure the crown-rump length and Doppler flow velocity waveform patterns of both UtAs. Serum concentrations of pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (β-hCG), A disintegrin and metalloprotease domain-containing protein-12 (ADAM-12), placental protein-13 (PP-13) and placental growth factor (PlGF) levels were measured in thawed specimens using an automated time-resolved fluorescence assay. Summary curves were created to describe normal ranges and trends over time. The data were analyzed with a linear mixed model with the log-transformed marker values as dependent variables. This allowed for flexible modeling of patterns over time. Sixty-eight pregnancies had an uneventful outcome, with the birth of an appropriate-for-gestational-age (AGA) infant. In these pregnancies serum PAPP-A, ADAM-12, PP-13 and PlGF levels increased with gestational age. The UtA-PI decreased and the mean arterial blood pressure remained constant. There were no significant correlations between maternal age, birth-weight percentile, gender and blood pressure and any of the biochemical markers. The serum markers were highly correlated with each other except for β-hCG. A negative correlation was found between most biomarkers and UtA-PI, especially from 10 weeks onwards. Serum concentrations of ADAM-12 and PP-13 were lower in a small-for-gestational-age (SGA) subgroup born at term (n = 6), the former statistically significantly (P = 0.031), the latter non-significantly (P = 0.054), whereas UtA-PI was significantly higher (P = 0.02). Biomarker concentrations in 12 women delivering a large-for-gestational age infant did not differ from those delivering AGA neonates. There is a relationship between biochemical markers of early placentation and downstream resistance to flow in the UtAs in low-risk uncomplicated pregnancies, indicating differences in placentation. In a small series of SGA infants born at term we could demonstrate differences as compared to normal pregnancies, with potential value for screening.

Homocysteine correlation with angiogenic factors and uterine blood flows in idiopathic recurrent spontaneous miscarriage

Homocysteine correlation with angiogenic factors and uterine blood flows in idiopathic recurrent spontaneous miscarriage

Serum placental growth factor and fms-like tyrosine kinase 1 during first trimester in Chinese women with pre-eclampsia – a case–control study

Objective. To investigate the association between first trimester maternal placental growth factor (PlGF) and fms-like tyrosine kinase 1 (sFlt-1) levels with subsequent development of pre-eclampsia (PE).Methods. This is a matched case–control study using stored serum samples collected from non-smoking Chinese women with singleton pregnancies who underwent first trimester screening for aneuploidy. Each case that developed PE was matched with a control whose maternal age, weight, gestational age and date of blood collection were within ±2 years, ±5 kg, ±1 day, and ±2 weeks of the index case, respectively. Non-parametric paired test was used to compare the PlGF and sFlt-1 levels. PlGF and sFlt-1 were transformed to their equivalent multiple of the median (MoM) using the matched control as the expected median value. The 95% confidence interval (CI) of the estimated median PlGF and sFlt-1 MoM in those with PE was determined.Results. The median PlGF level in the 27 study cases with PE was lower than that of the matched controls (42.9 pg/ml versus 59.8 pg/ml; p = 0.001). The median PIGF MoM was 0.71 (95% CI 0.63–0.92). There was no statistically significant difference in sFlt-1 levels between those with PE and their matched control (p = 0.648). The median sFlt-1 MoM was 1.01 (95% CI 0.65–1.3).Conclusions. Women who developed PE had lower serum PlGF levels but normal sFlt-1 levels in the first trimester.

Soluble Flt-1 and PlGF: New Markers of Early Pregnancy Loss?

Recent data have indicated a relationship between placental oxygen and angiogenic protein levels in the first trimester of normal pregnancies. Our objective was to investigate if maternal serum levels of angiogenic factors Soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1), soluble Endoglin and placental growth factor (PlGF) are altered in women with symptoms of threatened miscarriage (TM) and if they are predictive of a subsequent miscarriage. Blood samples were collected at 6–10 weeks from women presenting with TM (n = 40), from asymptomatic controls (n = 32) and from non- pregnant women in their luteal phase (n = 14). All samples were assayed for serum level of sFLT-1, PlGF, sEndoglin and HSP70 using commercial ELISAs. Samples were analysed retrospectively on the basis of pregnancy outcome. TM group included 21 women with a normal pregnancy outcome and 19 with subsequent complete miscarriage. The latter subgroup had significantly lower mean maternal serum (MS) sFlt-1 (83%, P<0.001) and PlGF (44%, P<0.001) compared to those with a normal pregnancy outcome. Asymptomatic control pregnant women had similar MS levels of sFlt-1 and PlGF compared to the TM patients with a normal outcome. The mean MS sFlt-1 (>10 fold) and MS PlGF (∼2 fold) levels were significantly (P<0.001) higher in control pregnant women compared to the non-pregnant group in the luteal phase of the menstrual cycle. Soluble Endoglin was not altered in the normal pregnant women compared to non pregnant women, although lower in the TM subgroup with a subsequent miscarriage (∼25%, P<0.001) compared to TM with a live birth. There was no significant difference in the mean MS HSP 70 levels between the different groups. This study shows that sFlt1 and PlGF MS levels are increased by several folds in early pregnancy and that MS sFlt-1 and MS PlGF are markedly decreased in threatened miscarriage patients who subsequently have a miscarriage suggesting these proteins are sensitive predictive markers of subsequent pregnancy loss.

Placental Growth Factor in Patients with Decreased Renal Function

Background: Patients with decreased renal function are characterized by high cardiovascular morbidity and mortality due to complications of premature atherosclerosis. Placental growth factor (PlGF) is a proatherogenic cytokine and new biomarker of cardiovascular events. The aim of this study was to determine PlGF levels and describe their relationship to renal function and risk factors of atherogenesis in patients with decreased renal function. Methods: The study group consisted of 114 subjects: 45 patients with various degrees of decreased renal function (CHRI), 31 long-term hemodialysis (HD) patients, and 38 age-matched healthy control subjects. PlGF was assessed immunochemically (enzyme-linked immunosorbent assay) and routine biochemical parameters were measured using standard laboratory methods. Results: PlGF levels were significantly increased in CHRI and HD patients compared to controls (10.5 ± 3.3 pg/mL in CHRI patients and 11.5 ± 3.4 pg/mL HD patients vs. 8.1 ± 1.8 pg/mL in controls, both p < 0.0001). In CHRI patients, PlGF was detectable in the urine, and its urine concentration correlated with its serum levels. In HD patients, PlGF correlated with low-density lipoproteins (r = 0.36, p < 0.05), but was not related to C-reactive protein levels. Higher levels of PlGF were found in CHRI patients with cardiovascular disease, compared with those free of such complication. Conclusions: PlGF levels are increased in patients with decreased kidney function. PlGF is detectable in the urine, and serum and urine levels of PlGF are significantly interrelated. It is higher in CHRI patients with cardiovascular disease. Further studies are required to demonstrate the usefulness and significance of PlGF in patients with chronic kidney disease.

Impact of soluble fms-like tyrosine kinase-1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction

Angiogenic factors play an important role in the development of atherosclerosis and show pronounced changes during acute myocardial infarction (AMI). We analysed the impact of placental growth factor (PlGF) and its endogen opponent, soluble fms-like tyrosine kinase-1 (sFlt-1), on clinical outcome and the early diagnosis of AMI. This multicentre study enrolled patients presenting with symptoms suggestive of AMI. The final diagnosis was adjudicated by two independent physicians. Levels of sFlt-1 and PlGF were compared with results of a standard troponin T and a novel high-sensitive troponin (hsTnT) assay. Of the 763 patients enrolled, 132 were diagnosed with AMI. Multivariable Cox regression analysis demonstrated sFlt-1 >84 ng/L [hazard ratios (HR) 2.6, 95% confidence intervals (CI) 1.2-5.4, P=0.01] and PlGF >20 ng/L (HR 3.6, 95% CI 1.3-10.4, P=0.02) as predictors for mortality during 1-year follow-up, independent from information provided by troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). However, only sFlt-1 persisted as independent predictor for mortality when analysed together with hsTnT and NT-proBNP, and after adjusting for significant clinical parameters. For the diagnosis of AMI, the combination of troponin T and sFlt-1 improved the performance of troponin T alone and led to a negative predictive value of 98.3% already at time of presentation. However, sFlt-1 and PlGF added only limited diagnostic information when used together with hsTnT. Only sFlt-1 but not PlGF provides overall independent prognostic information in patients presenting with symptoms suggestive of AMI. After the introduction of hsTnT in clinical routine, sFlt-1 and PlGF can only add limited diagnostic information for the detection or exclusion of AMI. ClinicalTrials.gov, NCT00470587.

Corticosteroids Modulate Angiogenic Soluble Factors in Ulcerative Colitis Patients

The aim of this study was to compare angiogenic factors in serum levels of active ulcerative colitis (UC) patients and in healthy controls, and to analyze these angiogenic levels depending on the achievement of remission after oral corticosteroid treatment throughout treatment, and according to the Truelove-Witts activity index. Blood samples were collected from 13 patients receiving oral corticosteroids for treatment of UC flares at three different intervals--baseline, during, and after treatment--and from 26 healthy controls. Vascular endothelial growth factor (VEGF), placental growth factor (PlGF), VEGF receptor 1 (VEGFR1), angiopoietins (Ang) 1 and 2, and its receptor Tie2 were assayed by ELISA. While VEGF and Ang2 levels in UC patients were higher than in healthy controls (P < 0.05), UC patients showed lower levels of Ang1 than healthy individuals (P < 0.05). In UC patients who achieved clinical remission after corticosteroid treatment, a statistically significant higher baseline serum level of PlGF was observed (22 ± 5 vs. 18 ± 2; P < 0.05). Angiogenic factor levels varied during treatment; however, they did not show a statistically significant correlation to the activity of the disease. VEGF, Ang1, and Ang2 levels showed statistically significant differences between UC patients and healthy controls. Although determination of PlGF serum levels before corticosteroid treatment might be helpful to anticipate the response by UC patients, no angiogenic pattern that could accurately predict "a priori" this response to corticosteroid treatment was observed. Corticosteroids altered temporarily circulating levels of VEGF, angiopoietins and Tie2. No correlation was found between systemic levels of angiogenic factors and the clinical activity of UC.

Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia

The purpose of this study was to determine whether increased serum soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF) levels in pre-eclampsia are related to the clinical features and laboratory parameters of the patients, including markers of inflammation, endothelial activation and injury, oxidative stress and trophoblast debris. A total of 54 pre-eclamptic patients, 58 healthy pregnant and 52 healthy non-pregnant women were involved in this case-control study. Serum sFlt-1 and PlGF levels were measured by electrochemiluminescence immunoassay. Serum levels of sFlt-1 and PlGF were significantly higher in pre-eclamptic patients and healthy pregnant women than in healthy non-pregnant women. In addition, pre-eclamptic patients had significantly higher sFlt-1 levels and significantly lower PlGF concentrations compared with healthy pregnant women. According to the subgroup analyses, sFlt-1 levels were significantly higher in severely pre-eclamptic patients than in those with mild pre-eclampsia, whereas pre-eclamptic patients with fetal growth restriction or preterm onset of the disease had significantly lower PlGF concentrations compared with those without intrauterine growth restriction or with a disease onset at term. In the pre-eclamptic group, there were significant positive correlations between serum sFlt-1 levels and systolic and diastolic blood pressure, serum levels of blood urea nitrogen and creatinine, as well as plasma levels of von Willebrand factor antigen, fibronectin and cell-free fetal DNA. Furthermore, serum PlGF concentrations of pre-eclamptic patients showed significant positive correlations with gestational age at disease onset and delivery, as well as with fetal birth weight, and significant inverse correlations with levels of blood urea nitrogen, creatinine and fibronectin. In conclusion, increased serum sFlt-1 and decreased PlGF levels are associated with blood pressure, renal and endothelial dysfunction, trophoblast deportation, as well as with a shorter duration of pregnancy, fetal growth restriction, the severity and preterm onset of the disease in pre-eclampsia. These findings indicate the central role of an angiogenic imbalance in the pathogenesis of this pregnancy-specific disorder.

Effect of long-term storage on placental growth factor and fms-like tyrosine kinase 1 measurements in samples from pregnant women

Objective. To assess the effect of storage time on the stability of placental growth factor (PlGF) and fms-like tyrosine kinase 1 (sFlt-1) levels in frozen serum samples from pregnant women.Methods. This is a matched case–control study using fresh and stored serum samples collected at 6, 12, 18, 24, 30 and 36 months prior to the collection of the fresh samples and frozen at –80°C. Forty-eight samples from each of the seven time-groups were matched for non-smoking Chinese, maternal weight, singleton-term pregnancy without major obstetric complications and extracted for PlGF and sFlt-1 assays. Multivariate analysis was performed to assess residual effects of the case-matching procedure. ANOVA was used to assess the effects of storage time.Results. Multivariate analysis of the 336 samples indicated that log10PlGF was positively correlated with parity (p = 0.014) and gestational age (p = 0.029), while log10sFlt-1 was inversely correlated with parity (p = 0.018). After correcting for the residual effect of gestation and parity, ANOVA showed no significant difference in PlGF and sFlt-1 levels between the fresh samples and all stored samples (p = 0.410 and p = 0.158, respectively).Conclusions. Serum PlGF and sFlt-1 levels are stable for at least 3 years when stored at –80°C. Parity is an independent factor of PlGF and sFlt-1 levels. PlGF levels are lower and sFlt-1 levels are higher in nulliparous women compared to multiparous.

Early-pregnancy soluble Fas levels in idiopathic small-for-gestational-age pregnancies

We sought to determine first- and second-trimester serum soluble Fas (sFas) and placental growth factor (PlGF) levels in idiopathic small-for-gestational-age (SGA) pregnancies. We measured sFas and PlGF levels in women who delivered SGA infants uncomplicated by preeclampsia and in control subjects. For sFas there were 34 cases and 318 control subjects in the first trimester and 9 cases and 11 control subjects in the second trimester. For PlGF there were 31 cases and 281 control subjects in the first trimester and 8 cases and 11 control subjects in the second trimester. SGA pregnancies had lower sFas levels than control subjects in the second trimester (3703 + or - 209 pg/mL vs 4562 + or - 241 pg/mL; P = .015), but not in the first trimester (4892 + or - 191 pg/mL vs 4971 + or - 177 pg/mL; P = .68). There was no difference in PlGF levels between SGA and normal pregnancies in both trimesters. Serum sFas levels were lower in idiopathic SGA pregnancies in the second trimester, but not in the first. There was no difference in serum PlGF levels in either trimester.

Maternal serum placental growth factor and soluble fms‐like tyrosine kinase 1 as early predictors of preeclampsia

Abstract The aim of this study was to identify pregnant women at risk of preeclampsia (PE) before clinical manifestations appeared using a panel of serum markers. We recruited 240 consecutive women who presented for antenatal care. We investigated whether serum levels of placental growth factor (PlGF), its inhibitor, soluble fms-like tyrosine kinase-1 (sFlt-1), measured at 13-16 weeks gestation and the expression of fms-like tyrosine kinase-1 (Flt-1) in the maternal neutrophils measured by flow cytometry could be predictive of the subsequent development of PE. Serum PlGF levels were found to be significantly lower among women who developed PE than patients with gestational hypertension or patients in the control group (p < 0.001). In contrast, serum sFlt1 levels were most elevated in patients who developed PE versus those with gestational hypertension or the control group (p < 0.001). Serum levels of neutrophil-Flt-1, however, were lower in women who developed PE than in those with gestational hypertension or those in the control group (p < 0.001). Increased serum levels of sFlt-1, decreased levels of neutrophil-Flt-1, and decreased levels of PlGF may predict women at risk of developing PE later in pregnancy.

Endostatin, Placental Growth Factor, and Fibroblast Growth Factors-1 and -2 in the Sera of Patients with Primary Osteosarcomas

Serum levels of endostatin, placental growth factor (PlGF), and fibroblast growth factors-1 and -2 (FGF-1 and FGF-2) were measured in 58 patients with primary osteosarcomas before therapy and in 21 healthy subjects. The incidence of serum FGF-1 in bone tumors was 2.5 times higher than in healthy individuals (p=0.004); significant levels of FGF-2, PlGF, and endostatin were detected in all examined subjects. The mean serum level of endostatin in healthy individuals was significantly lower than in the total group of patients with bone tumors (p=0.005). The level of FGF-1 in osteosarcomas was significantly higher than in chondrosarcomas (p<0.05). No appreciable differences in FGF-2 levels were detected in patients with tumors of different histological structure. The mean serum content of PlGF was virtually the same in healthy individuals and patients with bone tumors. A significant relationship between serum PlGF level and maximum tumor size (p=0.008) was detected in osteosarcoma. No relationships between the levels of FGF-1, FGF-2, PlGF, and endostatin were detected in healthy subjects and patients with primary tumors of the bones. Differences in 3-year overall survival values of patients with bone sarcomas with different initial serum levels of FGF-1 and endostatin were detected.

Serum Vascular Endothelial Growth Factor/Soluble Vascular Endothelial Growth Factor Receptor 1 Ratio Is an Independent Prognostic Marker in Pancreatic Cancer

Tumor angiogenesis is the consequence of an imbalance between positive and negative angiogenic regulatory factors. We sought to determine the role of pretreated serum angiogenic factors, including vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and soluble vascular endothelial growth factor receptor 1 (sVEGFR-1), in predicting clinical outcome in patients with pancreatic cancer. We assessed pretreated serum VEGF, PlGF, and sVEGFR-1 levels in 92 patients with pancreatic adenocarcinoma and 60 healthy control subjects using an enzyme-linked immunosorbent assay. The correlation between these angiogenesis-related factors and clinicopathologic factors, including staging and overall survival, was analyzed. Serum levels of VEGF, PlGF, and sVEGFR-1 were significantly higher in patients with pancreatic cancer compared with those in controls (583.8 +/- 559.5 vs 187.63 +/- 393.32, 17.65 +/- 7.34 vs 10.93 +/- 1.21, and 50.94 +/- 51.17 vs 15.55 +/- 1.98 pg/mL, respectively; P < 0.0001). A reverse correlation was observed between sVEGFR-1 level and the advance of tumor stage. Cox regression analysis showed that the VEGF/sVEGFR-1 ratio was an independent predictor for pancreatic cancer survival. Higher VEGF/sVEGFR-1 ratio was significantly correlated with poor outcome in patents with pancreatic cancer. Vascular endothelial growth factor/sVEGF-1 ratio is an independent prognostic factor for survival in pancreatic cancer. Its significance should be assessed when considering antiangiogenic therapy in treating pancreatic cancer patients.