***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Schnitzler syndrome is a rare plasma cell disorder the pathogenesis of which is still not fully understood . We evaluated the circulating levels of four major  angiogenic cytokines ( VEGF , angiogenin , angiopoietin-1 and  angiopoietin-2 ) and six  bone remodeling markers ( sRANKL , osteoprotegerin , dickkopf-1 , CTX , osteocalcin and bone-specific alkaline phosphatase-bALP )  in 13 patients with Schnitzler syndrome . At diagnosis , patients had elevated angiogenic cytokines . The mean VEGF levels were almost 3.5-fold higher in Schnitzler syndrome compared to controls , while 10 of 13 patients had higher VEGF than the upper control value . Successful treatment led to a significant reduction in VEGF . Patients with Schnitzler syndrome had increased bone formation ( high bALP , osteocalcin and osteoprotegerin ) which was not balanced by an increase in bone resorption ( normal CTX and sRANKL ) . These data support a role for VEGF as a new minor criterion in the diagnosis and follow up of Schnitzler syndrome , while the uncoupling of bone remodeling in favor of bone formation justifies the presence of bone densification More than half of all cases of preeclampsia occur in healthy first-time pregnant women . Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints ( SCOPE ) study of low-risk nulliparous women . Forty-seven biomarkers identified on the basis of ( 1 ) association with preeclampsia , ( 2 ) a biological role in placentation , or ( 3 ) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sample d at 14 to 16 weeks ’ gestation from 5623 women . The cohort was r and omly divided into training ( n=3747 ) and validation ( n=1876 ) cohorts . Preeclampsia developed in 278 ( 4.9 % ) women , of whom 28 ( 0.5 % ) developed early-onset preeclampsia . The final model for the prediction of preeclampsia included placental growth factor , mean arterial pressure , and body mass index at 14 to 16 weeks ’ gestation , the consumption of ≥3 pieces of fruit per day , and mean uterine artery resistance index . The area under the receiver operator curve ( 95 % confidence interval ) for this model in training and validation cohorts was 0.73 ( 0.70–0.77 ) and 0.68 ( 0.63–0.74 ) , respectively . A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio , mean arterial pressure , any pregnancy loss < 10 weeks , and mean uterine artery resistance index ( area under the receiver operator curve [ 95 % confidence interval ] in training and validation cohorts , 0.89 [ 0.78–1.0 ] and 0.78 [ 0.58–0.99 ] , respectively ) . Neither model included pregnancy-associated plasma protein A , previously reported to predict preeclampsia in population s of mixed parity and risk . In nulliparous women , combining multiple biomarkers and clinical data provided modest prediction of preeclampsia Aim /hypothesisLeptin has been shown to regulate angiogenesis in animal and in vitro studies by upregulating the production of several pro-angiogenic factors , but its role in regulating angiogenesis has never been studied in humans . Methods The potential angiogenic effect of two doses of metreleptin ( 50 and 100 ng/ml ) was evaluated in vitro , using a novel three-dimensional angiogenesis assay . Fifteen healthy , normoleptinaemic volunteers were administered both a physiological ( 0.1 mg/kg ) and a pharmacological ( 0.3 mg/kg ) single dose of metreleptin , in vivo , on two different inpatient admissions separated by 1–12 weeks . Serum was collected at 0 , 6 , 12 and 24 h after metreleptin administration . Twenty lean women , with leptin levels < 5 ng/ml , were r and omised in a 1:1 fashion to receive either physiological replacement doses of metreleptin ( 0.04–0.12 mg/kg q.d . ) or placebo for 32 weeks . Serum was collected at 0 , 8 , 20 and 32 weeks after r and omisation . Proteomic angiogenesis array analysis was performed to screen for angiogenic factors . Circulating concentrations of angiogenin , angiopoietin-1 , platelet derived endothelial factor (PDGF)-AA , matrix metalloproteinase ( MMP ) 8 and 9 , endothelial growth factor ( EGF ) and vascular EGF ( VEGF ) were also measured . Results Both metreleptin doses failed to induce angiogenesis in the in vitro model . Although leptin levels increased significantly in response to both short-term and long-term metreleptin administration , circulating concentrations of angiogenesis markers did not change significantly in vivo . Conclusions /interpretationsThis is the first study that examines the effect of metreleptin administration in angiogenesis in humans . Metreleptin administration does not regulate circulating angiogenesis related factors in humans . Clinical trial registration : Clinical Trials.gov NCT00140205 and NCT00130117 . Funding : This study was supported by National Institutes of Health-National Center for Research Re sources grant M01-RR-01032 ( Harvard Clinical and Translational Science Center ) and grant number UL1 RR025758 . Funding was also received from the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785 , 79929 and 81913 , and AG032030 PURPOSE Accurate urine assays for bladder cancer detection would benefit patients and health care systems . Through extensive genomic and proteomic profiling of urine components we previously identified a panel of 8 biomarkers that can facilitate the detection of bladder cancer in voided urine sample s. In this study we confirmed this diagnostic molecular signature in a diverse multicenter cohort . MATERIAL S AND METHODS We performed a case-control , phase II study in which we analyzed voided urine from 102 subjects with bladder cancer and 206 with varying urological disorders . The urinary concentration of 8 biomarkers ( IL-8 , MMP-9 and 10 , PAI-1 , VEGF , ANG , CA9 and APOE ) was assessed by enzyme-linked immunosorbent assay . Diagnostic performance of the panel of tested biomarkers was evaluated using ROCs and descriptive statistical values , eg sensitivity and specificity . RESULTS Seven of the 8 urine biomarkers were increased in subjects with bladder cancer relative to those without bladder cancer . The 7 biomarkers were assessed in a new model , which had an AUROC of 0.88 ( 95 % CI 0.84 - 0.93 ) , and 74 % sensitivity and 90 % specificity . In contrast , the sensitivity of voided urine cytology and the UroVysion ® cytogenetic test in this cohort was 39 % and 54 % , respectively . Study limitations include analysis performed on banked urine sample s and the lack of voided urine cytology and cytogenetic test data on controls . CONCLUSIONS The study provides further evidence that the reported panel of diagnostic biomarkers can reliably achieve the noninvasive detection of bladder cancer with higher sensitivity than currently available urine based assays OBJECTIVE To investigate whether elevated urinary levels of vascular endothelial growth factor ( VEGF ) , carbonic anhydrase 9 ( CA9 ) , and angiogenin are associated with bladder cancer ( BCa ) . METHODS This was a case-control study in which voided urine sample s from 127 patients ( 63 control subjects and 64 patients with BCa ) were analyzed . The urinary concentrations of VEGF , CA9 , angiogenin , and bladder tumor antigen ( BTA ) were assessed using enzyme-linked immunosorbent assays . We used the area under the curve of receiver operating characteristic curves to determine the ability of VEGF , CA9 , and angiogenin to detect BCa in voided urine sample s. Data were also compared with the findings from a commercial enzyme-linked immunosorbent assay-based BCa detection assay ( BTA-Trak ) . The sensitivity , specificity , and positive and negative predictive values were calculated . RESULTS The urinary concentrations of VEGF , CA9 , angiogenin , and BTA were significantly elevated in those with BCa . VEGF was the most accurate urinary biomarker ( area under the curve 0.886 , 95 % confidence interval 0.8301 - 0.9418 ) . Furthermore , multivariate regression analysis highlighted VEGF ( odds ratio 5.90 , 95 % confidence interval 2.60 - 13.40 , P < .0001 ) as an independent variable . The sensitivity and specificity for VEGF ( 83 % sensitivity and 87 % specificity ) outperformed those for BTA ( 80 % sensitivity and 84 % specificity ) . CONCLUSION VEGF could be a valuable addition to voided urine sample analysis for the detection of BCa . Larger , prospect i ve studies are needed to determine the clinical utility of urinary VEGF and angiogenin as biomarkers in the noninvasive evaluation of patients with BCa OBJECTIVE Angiogenin ( ANG ) , a potent inducer of neovascularization , is secreted by some types of human tumor cells and appears crucial for their growth . This study was design ed with the aim to investigate any correlation between the serum angiogenin and the clinicopathological variables and furthermore evaluate the prognostic value of serum angiogenin in patients with breast cancer . MATERIAL AND METHODS Sixty-four consecutive patients with invasive breast cancer undergoing surgery were prospect ively included and evaluated . Venous blood sample s were collected before surgery . Sera were obtained by centrifugation and stored at -70 degrees C until assayed . The control group consisted of 16 patients with benign breast tumor ( 8 with fibrocystic disease and 8 with fibroadenoma ) .  Serum concentration of angiogenin  was measured by the quantitative s and wich enzyme immunoassay technique . The data on primary tumor staging , age , estrogen receptor , lymph node status , distant metastases and TNM staging were review ed and recorded . RESULTS The mean value of serum angiogenin in patients with invasive breast cancer was 2123.95 + /- 324.34 pg/ml and that of control group were 2108.16 + /- 398.20 pg/ml ( fibrocystic disease ) and 2010.27 + /- 318.40 pg/ml ( fibroadenoma ) . The difference was not significant ( p = 0.66 ) . Furthermore , with univariate analysis , there were no significant differences in serum angiogenin levels between the subgroups of the above-mentioned clinicopathological variables . CONCLUSION Serum angiogenin levels did not appear as a meaningful prognostic parameter for invasive breast cancer OBJECTIVE Our purpose was to compare angiogenin , lactate dehydrogenase ( LDH ) and fibronectin levels in mid-trimester amniotic fluid of patients with preterm and term deliveries and to find out their predictive values for preterm birth . STUDY DESIGN A prospect i ve cohort study was conducted in 55 pregnancies with singleton gestations that underwent amniocentesis at 15 - 20 weeks for st and ard genetic indications .  Amniotic fluid angiogenin , lactate dehydrogenase and fibronectin levels  were measured by enzyme-linked immunosorbent assay ( ELISA ) , radial immundiffusion technic and automated analyzer , respectively . RESULTS Five patients delivered preterm , five developed signs or symptoms of threatened preterm labor and 45 had term delivery after an uneventful pregnancy . Demographic data were not significantly different . Amniotic fluid angiogenin and lactate dehydrogenase levels were significantly higher in patients with preterm than term deliveries ( P<0.001 and 0.02 , respectively ) . Receiver-operator characteristic curve analysis showed that the amniotic fluid angiogenin had the best screening efficiency in predicting preterm delivery . An angiogenin level of 35ng/ml was the optimal cut-off value for the prediction of preterm delivery , with a sensitivity of 100 % and specificity of 91 % . CONCLUSION Second-trimester angiogenin is found to be quite effective in the prediction of preterm delivery . Preexisting intrauterine ischemia may be an important risk factor for preterm delivery and already be present in the early mid-trimester OBJECTIVE To investigate the role of the angiogenic factors , vascular endothelial growth factor ( VEGF ) and angiogenin in the pathophysiology of preeclampsia and how their concentrations correlate with the severity of the disease and fetal outcome . PATIENTS AND METHODS A prospect i ve study was carried out on 71 pregnant patients with preeclampsia and 20 pregnant normotensive controls . Maternal serum levels of VEGF and angiogenin were determined in all cases by enzyme imm 
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We noted no significant differences in serum ANG levels between patients and healthy controls , except in cases in which patients suffered from cancer or cardiovascular diseases .
The serum ANG concentrations were significantly higher in patients who developed colorectal cancer , acute myeloid leukemia , multiple myeloma , myelodysplastic syndromes , and heart failure than those in healthy controls .
Conclusion ANG has the potential of being a serum biomarker for cancers and cardiovascular diseases