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1.
BMC Cancer ; 17(1): 419, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28619014

RESUMO

BACKGROUND: Angiogenesis is essential for the progression and metastatic spread of solid tumours. Expression of vascular endothelial growth factor (VEGF) has been linked to poor survival among osteosarcoma patients but the clinical relevance of monitoring blood and urine angiogenic factors is uncertain. The aim of this study was to determine the prognostic significance of blood VEGF and blood and urinary basic fibroblast growth factor (bFGF) levels in osteosarcoma patients, both at diagnosis and during treatment. METHODS: Patients with localised or metastatic osteosarcoma enrolled in OS2005 and OS2006 studies between 2005 and 2011 were prospectively included in this study. VEGF and bFGF levels in serum and plasma and bFGF levels in urine were measured by ELISA at diagnosis, before surgery, and at the end of treatment. Endpoints considered for the prognostic analysis were histological response, progression-free and overall survival. Kruskal-Wallis tests were used to compare the distribution of baseline biomarker values across the different subgroups, and paired sample Wilcoxon rank tests were used to analyze changes over time. Association between biomarker levels and outcomes were assessed in multivariable models (logistic regression for histologic response, and Cox models for survival). RESULTS: Samples were available at diagnosis for 269 patients (54% males; age ≤ 18 years: 73%; localised disease in 68%, doubtful lung lesions in 17%, and metastases in 15%). High serum VEGF and bFGF levels were observed in respectively 61% and 51% of patients. Serum and plasma VEGF values were not strongly correlated with one another (r = 0.53). High serum and plasma VEGF levels were significantly more frequent in patients with large tumours (≥10 cm; p = 0.003 and p = 0.02, respectively). VEGF levels fell significantly during pre-operative chemotherapy (p < 0.0001). No significant correlation was found between this variation and either the histological response, progression-free survival or overall survival (p = 0.26, p = 0.67, and p = 0.87, respectively). No significant association was found between blood or urinary bFGF levels and clinical characteristics, histological response, or survival. CONCLUSIONS: Levels of VEGF and bFGF angiogenic factors are high in most osteosarcoma patients, but have no significant impact on response to chemotherapy or outcome in this large prospective series. OS 2006 TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT00470223; date of registration: May 3th 2007.


Assuntos
Indutores da Angiogênese/sangue , Indutores da Angiogênese/urina , Biomarcadores , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/mortalidade , Osteossarcoma/metabolismo , Osteossarcoma/mortalidade , Adolescente , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/terapia , Criança , Feminino , Fator 2 de Crescimento de Fibroblastos/sangue , Fator 2 de Crescimento de Fibroblastos/urina , Humanos , Masculino , Estadiamento de Neoplasias , Osteossarcoma/diagnóstico , Osteossarcoma/terapia , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Carga Tumoral , Fatores de Crescimento do Endotélio Vascular/sangue , Fatores de Crescimento do Endotélio Vascular/urina , Adulto Jovem
2.
J Neurosurg Pediatr ; 18(4): 396-407, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27314542

RESUMO

OBJECTIVE The authors report the use of urinary biomarkers as a novel, noninvasive technique to detect juvenile pilocytic astrocytomas (JPAs), capable of distinguishing JPAs from other CNS diseases, including other brain tumors. Preliminary screening of an array of tumors implicated proteases (including matrix metalloproteinases [MMPs]) and their inhibitors (tissue inhibitors of metalloproteinase [TIMPs]) as well as growth factors (including basic fibroblast growth factor [bFGF]) as candidate biomarkers. These data led the authors to hypothesize that tissue inhibitor of metalloproteinase 3 (TIMP3) and bFGF would represent high-probability candidates as JPA-specific biomarkers. METHODS Urine was collected from 107 patients, which included children with JPA (n = 21), medulloblastoma (n = 17), glioblastoma (n = 9), arteriovenous malformations (n = 25), moyamoya (n = 14), and age- and sex-matched controls (n = 21). Biomarker levels were quantified with enzyme-linked immunosorbent assay, tumor tissue expression was confirmed with immunohistochemical analysis, and longitudinal biomarker expression was correlated with imaging. Results were subjected to univariate and multivariate statistical analyses. RESULTS Using optimal urinary cutoff values of bFGF > 1.0 pg/µg and TIMP3 > 3.5 pg/µg, multiplexing bFGF and TIMP3 predicts JPA presence with 98% accuracy. Multiplexing bFGF and MMP13 distinguishes JPA from other brain tumor subtypes with up to 98% accuracy. Urinary biomarker expression correlated with both tumor immunohistochemistry and in vitro tumor levels. Urinary bFGF and TIMP3 decrease following successful tumor treatment and correlate with changes in tumor size. CONCLUSIONS This study identifies 2 urinary biomarkers-bFGF and TIMP3-that successfully detect one of the most common pediatric brain tumors with high accuracy. These data highlight potential benefits of urinary biomarkers and support their utility as diagnostic tools in the treatment of children with JPA.


Assuntos
Astrocitoma/urina , Neoplasias Encefálicas/urina , Fator 2 de Crescimento de Fibroblastos/urina , Inibidor Tecidual de Metaloproteinase-3/urina , Malformações Arteriovenosas/urina , Biomarcadores Tumorais/urina , Linhagem Celular Tumoral , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Metaloproteinase 13 da Matriz/urina , Meduloblastoma/urina , Doença de Moyamoya/urina , Análise Multivariada
3.
Am J Reprod Immunol ; 73(5): 437-44, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25521546

RESUMO

PROBLEM: Severe preeclampsia has been independently linked to complement dysregulation and angiogenic imbalance; however, the relationship between complement and angiogenic factors in human pregnancy is unclear. METHOD OF STUDY: Utilizing existing biomarkers, our study sought to better understand this relationship in active disease. We performed a case-control study, enrolling 25 cases with severe preeclampsia, 25 controls with chronic hypertension, and 25 healthy controls without hypertension. Levels of complement components (C3a, C5a, and C5b-9) and angiogenic markers [basic fibroblast growth factor (bFGF), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), and soluble fms-like tyrosine kinase-1 (sFlt-1)] were measured simultaneously. RESULTS: Compared to both hypertensive and non-hypertensive controls, severe preeclampsia was associated with increased plasma sFlt-1, decreased plasma VEGF and PlGF, decreased urinary PlGF, and increased urinary C5b-9. Urinary marker C5b-9 correlated strongly with the anti-angiogenic condition. In subjects with detectable urinary excretion of C5b-9, median plasma levels of sFlt-1 were significantly greater (32,029 versus 4556 pg/mL, P < 0.0001) and levels of PlGF (15.6 versus 226 pg/mL, P < 0.0001) and VEGF (119 versus 153 pg/mL, P = 0.001) were significantly lower. CONCLUSION: More so than plasma complement markers, urinary C5b-9 may a useful measure to link complement dysregulation with angiogenic imbalance in severe preeclampsia.


Assuntos
Complexo de Ataque à Membrana do Sistema Complemento/urina , Pré-Eclâmpsia/urina , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Fator 2 de Crescimento de Fibroblastos/urina , Seguimentos , Humanos , Fator de Crescimento Placentário , Gravidez , Proteínas da Gravidez/urina , Fator A de Crescimento do Endotélio Vascular/urina , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/urina
4.
Pediatr Nephrol ; 28(11): 2189-98, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23872928

RESUMO

BACKGROUND: Acute kidney injury (AKI) increases the morbidity of critically ill children. Thus, it is necessary to identify better renal biomarkers to follow the outcome of these patients. This prospective case-control study explored the clinical value of a urinary biomarker profile comprised of neutrophil gelatinase lipocalin (uNGAL), fibroblast growth factor-2 (uFGF-2), and epidermal growth factor (uEGF) to follow these patients. METHODS: Urine samples were collected from 21 healthy children, and 39 critically ill children (mean age 7.5 years ± 6.97 SD) admitted to a pediatric intensive care unit with sepsis or requiring extra corporeal membrane oxygenation (ECMO). uNGAL, uFGF-2, and uEGF levels were measured using ELISA kits during the first 24 h of admission to PICU, at peak of illness, and upon resolution of the critical illness. RESULTS: On admission, the uNGAL and uFGF-2 levels were increased, and the uEGF levels were decreased, in critically ill children with AKI (n = 19) compared to those without AKI (n = 20), and healthy controls. A biomarker score using the combined cut-off values of uNGAL, uFGF-2, and uEGF (AUC = 0.90) showed the highest specificity to identify children with AKI, relative to each biomarker alone. uNGAL and uFGF-2 on admission showed high sensitivity and specificity to predict mortality (AUC = 0.82). CONCLUSIONS: The biomarker profile comprised of uNGAL, uFGF-2, and uEGF increased the specificity to detect AKI in critically ill children, when compared to each biomarker used alone. uNGAL and uFGF-2 may also predict the risk of death. Further validation of these findings in a large sample size is warranted.


Assuntos
Injúria Renal Aguda/urina , Fator de Crescimento Epidérmico/urina , Fator 2 de Crescimento de Fibroblastos/urina , Injúria Renal Aguda/mortalidade , Biomarcadores , Estudos de Casos e Controles , Criança , Pré-Escolar , Creatinina/sangue , Cuidados Críticos , Estado Terminal , Oxigenação por Membrana Extracorpórea , Feminino , Gelatinases/sangue , Humanos , Lactente , Tempo de Internação , Lipocalinas/sangue , Masculino , Neutrófilos/enzimologia , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Sepse/complicações , Sepse/urina , Análise de Sobrevida
5.
Pediatr Nephrol ; 28(11): 2179-88, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23783654

RESUMO

BACKGROUND: The goal of this study was to assess the value of a urinary biomarker profile comprised of neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-2 (FGF-2), and epidermal growth factor (EGF), to detect acute kidney injury (AKI) in critically ill neonates. METHODS: We conducted a prospective cohort pilot study of at-risk neonates treated in a level IIIC neonatal intensive care unit (NICU) with therapeutic hypothermia (HT) (n = 25) or extracorporeal membrane oxygenation (ECMO) (n = 10). Urine was collected at baseline, 48 h of illness, and > 24 h post-recovery of their corresponding treatments. Control samples were collected from 27 healthy newborns. The data were expressed as urinary concentrations and values normalized for urinary creatinine. AKI was defined as the presence of oliguria >24 h and/or elevated serum creatinine (SCr), or the failure to improve the estimated creatinine clearance (eCCL) by >50% post-recovery. Non-parametric statistical tests and ROC analyses were used to interpret the data. RESULTS: Fifteen at-risk newborns had AKI. In the first 48 h of illness, the urinary levels of NGAL and FGF-2 had high sensitivity but poor specificity to identify neonates with AKI. At recovery, low urinary EGF levels identified neonates with AKI with a sensitivity of 74% and specificity of 84%. Overall, in the early stages of a critical illness, the urinary levels of NGAL and FGF-2 were sensitive, but not specific, to identify neonates at risk of AKI. Low EGF levels post-recovery identified critically ill neonates with AKI. CONCLUSIONS: These findings require validation in larger prospective studies.


Assuntos
Injúria Renal Aguda/urina , Biomarcadores/urina , Injúria Renal Aguda/terapia , Proteínas de Fase Aguda/urina , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Cuidados Críticos , Estado Terminal , Fator de Crescimento Epidérmico/urina , Oxigenação por Membrana Extracorpórea , Feminino , Fator 2 de Crescimento de Fibroblastos/urina , Humanos , Hipotermia Induzida , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Lipocalina-2 , Lipocalinas/urina , Masculino , Projetos Piloto , Estudos Prospectivos , Proteínas Proto-Oncogênicas/urina , Curva ROC , Equilíbrio Hidroeletrolítico/fisiologia
6.
Vasc Med ; 18(3): 122-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23720035

RESUMO

Sturge-Weber syndrome (SWS) consists of a capillary-venous vascular malformation of the brain, skin and eye. Urine vascular biomarkers have been demonstrated to be abnormal in other vascular anomalies and to correlate with clinical severity and progression. The current study investigated the use of urinary matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) levels to non-invasively monitor the progression of SWS. Fifty-four urine samples were collected from patients seen at the Hunter Nelson Sturge-Weber Center at Kennedy Krieger Institute. Urine was analyzed for MMP-2, MMP-9, VEGF and bFGF levels and correlated with clinical outcome at the time of urine collection (n = 48) and 1 year following urine collection (n = 22). Analysis revealed that MMP-2 (p = 0.033) and MMP-9 (p = 0.010) were significantly more likely to be present in the urine of SWS subjects compared to controls and that bFGF was significantly more likely to be present at abnormal levels (p = 0.005). MMP-2 correlated with a more severe clinical score at the time of urine collection, while both MMP-2 and MMP-9 levels correlated with greater disease severity at time of collection. bFGF levels correlated with improved clinical score 1 year after urine collection. These results suggest that MMP-2 and MMP-9 levels may be useful in assessing SWS progression, as well as indicating which patients might benefit from more aggressive treatment, while bFGF levels may be useful in judging the efficacy of neurologic treatment in SWS.


Assuntos
Fator 2 de Crescimento de Fibroblastos/urina , Metaloproteinase 2 da Matriz/urina , Metaloproteinase 9 da Matriz/urina , Síndrome de Sturge-Weber/urina , Fator A de Crescimento do Endotélio Vascular/urina , Adolescente , Adulto , Biomarcadores Tumorais/urina , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Medição de Risco , Síndrome de Sturge-Weber/diagnóstico , Adulto Jovem
7.
Ter Arkh ; 84(6): 36-40, 2012.
Artigo em Russo | MEDLINE | ID: mdl-22997916

RESUMO

AIM: To assess the relation between urinary excretion of profibrotic and antifibrotic growth factors, albuminuria and glomerular fibrosis in type 1 diabetic patients. MATERIALS AND METHODS: 64 patients with diabetes were examined, including 25 ones with normal albumin excretion rate (AER), 30 microalbuminuric and 9 macroalbuminuric patients. Urinary excretion of type IV collagen, transforming growth factor-beta 1] (TGF-beta 1), tumor necrosis factor-alpha (TNF-alpha), fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF) and bone morphogenetic protein-7 (BMP-7) was determined by ELISA and compared to control (10 healthy subjects). Renal biopsy specimens were assessed in 7 patients with normal AER and in 14 microalbuminuric patients. RESULTS: Type IV collagen, TGF-beta1 and TNF-alpha excretion was increased significantly in patients with micro- and macroalbuminuria as compared to control (all p<0.05). Excretion of FGF-2 was increased in macroalbuminuric patients only (p=0.003). No marked changes in excretion of antifibrotic growth factors (HGF and BMP-7) were observed. TNF-alpha and FGF-2 correlated positively with urinary type IV collagen (r=0.37 and r=0.31, respectively). The presence of glomerular fibrosis in renal biopsy specimens was associated with higher excretion of TGF-beta1, TNF-alpha and FGF-2 (all p<0.05). CONCLUSION: The results suggest that unbalance between profibrotic and antifibrotic growth factors in the kidneys plays an important role in pathogenesis of diabetic nephropathy. Urinary TGF-beta1, TNF-alpha and FGF-2 may offer new possibilities for detection of renal fibrosis in diabetic patients.


Assuntos
Colágeno Tipo IV/urina , Diabetes Mellitus Tipo 1/urina , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/urina , Fator 2 de Crescimento de Fibroblastos/urina , Fator de Crescimento Transformador beta1/urina , Fator de Necrose Tumoral alfa/urina , Adolescente , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/patologia , Nefropatias Diabéticas/etiologia , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Phlebology ; 26(5): 191-6, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21597045

RESUMO

OBJECTIVE: To investigate the role of serum basic fibroblast growth factor (bFGF), estradiol (E2) and urine bFGF in differentiating infantile haemangiomas from vascular malformations. METHOD: 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. RESULTS: 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). CONCLUSION: 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.


Assuntos
Estradiol/sangue , Fator 2 de Crescimento de Fibroblastos/sangue , Fator 2 de Crescimento de Fibroblastos/urina , Hemangioma/diagnóstico , Malformações Vasculares/diagnóstico , Estudos de Casos e Controles , Pré-Escolar , Fenda Labial/patologia , Fissura Palatina , Diagnóstico Diferencial , Feminino , Hemangioma/sangue , Humanos , Lactente , Masculino , Estudos Prospectivos , Radioimunoensaio , Malformações Vasculares/sangue
9.
Zhonghua Yi Xue Za Zhi ; 91(16): 1092-5, 2011 Apr 26.
Artigo em Chinês | MEDLINE | ID: mdl-21609589

RESUMO

OBJECTIVE: To evaluate the role of serum vascular endothelial growth factor (VEGF) and urine basic fibroblast growth factor (bFGF) in the differential diagnosis of vascular anomalies by receiver operating characteristic curve. METHODS: Using the method of enzyme linked immunosorbent assay (ELISA), 364 cases of various vascular anomalies (proliferating hemangiomas, n = 146; hemangiomas, n = 106; vascular malformations, n = 112) and 440 cases of various vascular anomalies (proliferating hemangiomas, n = 154; involuting hemangiomas, n = 148; vascular malformations, n = 138) subjects were examined for the serum levels of VEGF and the urine bFGF respectively. Nonparametric statistical tests were used for data analysis. The VEGF levels of proliferating hemangioma, involuting hemangioma, vascular malformation and control groups were analyzed by the Kruskal-Wallis test. When there was significance (P < 0.05), a subgroup analysis was performed by the Mann-Whitney U test. A receiver operator characteristic (ROC) curve was constructed for both the serum levels of VEGF and urine bFGF to determine the optimal diagnostic cut-off to differentiate proliferating hemangioma from involuting hemangioma, vascular malformation and controls. RESULTS: The serum level of VEGF and the urine bFGF in proliferating hemangiomas were significantly higher than those in involuting hemangiomas, vascular malformations and negative controls (P < 0.01). And the differences among the latter three groups were not statistically significant (P > 0.05). The optimal diagnostic cut-off point of serum VEGF and urine bFGF to differentiate proliferating hemangioma from involuting hemangioma, vascular malformation and controls was 99.6 pg/mg and 0.16 ng/mmol respectively. The area under ROC curve, the sensitivity and specificity were 99.7%, 99.3%, 99.7% and 91.9%, 98.7%, 71.1% respectively. The differences of the area under ROC curve of serum VEGF and urine bFGF showed no statistical significance (P > 0.05). CONCLUSION: Serum VEGF and urine bFGF are helpful for differentiating proliferating hemangioma from involuting hemangioma, vascular malformation and controls. Both parameters have higher values of clinical application.


Assuntos
Fator 2 de Crescimento de Fibroblastos/urina , Doenças Vasculares/diagnóstico , Fatores de Crescimento do Endotélio Vascular/sangue , Criança , Diagnóstico Diferencial , Feminino , Humanos , Masculino
11.
Clin Biochem ; 43(10-11): 863-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20362567

RESUMO

OBJECTIVES: Dysregulation of angiogenesis has been proposed to play a central role in hemangioma pathogenesis. The aim of the study was to determine the peripheral and local serum levels of bFGF in patients with hemangiomas and vascular malformations (VM). DESIGN AND METHODS: The study group consisted of 52 children with infantile hemangioma, 14 with VM and 36 healthy patients. bFGF serum levels were analyzed by an ELISA assay. Urinary bFGF was determined in 11 individuals with hemangioma. RESULTS: The serum peripheral bFGF concentrations in children with proliferating hemangiomas were lower than in healthy controls (p=0,03). There was no correlation between the measured cytokine level and hemangioma size, as well as patients' age. The serum local bFGF levels in 29 children with hemangiomas were higher than in the peripheral blood (p=0.022). Urinary bFGF in hemangioma patients did not differ statistically from healthy controls. CONCLUSIONS: (1) Determination of bFGF serum levels is not helpful in differentiating the phases of hemangioma growth and distinguishing hemangiomas from VM; (2) serum levels of bFGF cannot distinguish between extrinsic and intrinsic theories of endothelial cell proliferation in hemangiomas.


Assuntos
Células Endoteliais/patologia , Fator 2 de Crescimento de Fibroblastos/sangue , Hemangioma Cavernoso/sangue , Malformações Vasculares/sangue , Adolescente , Proliferação de Células , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Fator 2 de Crescimento de Fibroblastos/urina , Hemangioma Cavernoso/diagnóstico , Hemangioma Cavernoso/urina , Humanos , Lactente , Masculino , Malformações Vasculares/diagnóstico , Malformações Vasculares/urina
12.
Kidney Int ; 76(2): 133-4, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19564854

RESUMO

Soler-García and collaborators show that changing levels of urinary biomarkers associated with the pathology of HIV-associated nephropathy may identify HIV-infected children at greatest risk for this complication. These changes appear relatively early in disease progression and remain responsive to antiviral therapy. Will these trends be borne out in a multicenter study?


Assuntos
Nefropatia Associada a AIDS/diagnóstico , Biomarcadores/urina , Fator de Crescimento Epidérmico/urina , Fator 2 de Crescimento de Fibroblastos/urina , Humanos , Metaloproteinase 2 da Matriz/urina
13.
Kidney Int ; 76(2): 207-14, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19357719

RESUMO

Human immunodeficiency virus (HIV)-infected children are at risk of developing several types of renal diseases, including HIV-associated nephropathy (HIVAN), which is usually seen during late stages of infection in children with a high viral load. This disease is defined by the presence of proteinuria associated with mesangial hyperplasia and/or global-focal segmental glomerulosclerosis combined with microcystic transformation of the renal tubules. Because HIVAN can have an insidious clinical onset, renal biopsy is the only definitive way of establishing a diagnosis. Given the risk of performing this procedure in HIV-infected children with other AIDS-defining illness, we sought to identify informative biomarkers such as growth factors in the urine of 55 HIV-infected children that might be predictive of the extent and activity of the renal lesions characteristic of HIVAN. We found that the levels of epidermal growth factor were lower in the urine of children with renal disease, whereas levels of fibroblast growth factor-2 and metalloproteinase-2 were higher as compared with those levels in infected children without renal disease. Similar changes were observed in HIV-Tg26 mice correlating with the progression of renal disease in this model of HIVAN. Our findings suggest that this urinary growth factor profile may be useful in facilitating the diagnosis of HIV-infected children at risk of developing HIVAN when interpreted in the appropriate clinical setting.


Assuntos
Nefropatia Associada a AIDS/diagnóstico , Peptídeos e Proteínas de Sinalização Intercelular/urina , Nefropatia Associada a AIDS/urina , Adolescente , Animais , Biomarcadores/urina , Estudos de Casos e Controles , Criança , Pré-Escolar , Fator de Crescimento Epidérmico/urina , Fator 2 de Crescimento de Fibroblastos/urina , Infecções por HIV/complicações , Humanos , Lactente , Metaloproteinase 2 da Matriz/urina , Camundongos , Camundongos Transgênicos , Valor Preditivo dos Testes , Carga Viral
15.
Urol Int ; 82(1): 43-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19172096

RESUMO

OBJECTIVES: To investigate the alterations of urine transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) following bladder outlet obstruction (BOO) in rats and to determine their correlation with the impaired detrusor contractibility. METHODS: Wistar rats were divided into control, 2-week BOO 6-week and BOO groups. Impaired detrusor contractibility was quantified by measuring detrusor contraction force (DCF) of detrusor strip stimulated by carbachol. The enzyme-linked immunosorbent assay method was used to determine the urine levels of the 2 factors. Correlation analysis was conducted between DCF and urine levels of the 2 factors to see if there was an association between them after BOO. RESULTS: DCF was found to be significantly lower in the 6-week BOO group than in the 2-week BOO and control groups. There is no significant difference regarding urine TGF-beta1 between the 2-week BOO and control groups (p > 0.05). Urine TGF-beta1 level in the 6-week BOO group was significantly higher than in the 2-week BOO (p < 0.05) and control groups (p < 0.05). There existed a negative correlation between DCF and urine TGF-beta1 (p < 0.05). CONCLUSIONS: In an animal model, our results have suggested the potential role of urine TGF-beta1 as a noninvasive biomarker to predict detrusor contractibility after BOO.


Assuntos
Fator 2 de Crescimento de Fibroblastos/urina , Contração Muscular , Fator de Crescimento Transformador beta1/urina , Obstrução do Colo da Bexiga Urinária/urina , Bexiga Urinária/fisiopatologia , Animais , Biomarcadores/urina , Carbacol/farmacologia , Agonistas Colinérgicos/farmacologia , Modelos Animais de Doenças , Feminino , Contração Muscular/efeitos dos fármacos , Tamanho do Órgão , Ratos , Ratos Wistar , Fatores de Tempo , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Obstrução do Colo da Bexiga Urinária/patologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia
16.
Zhonghua Yi Xue Za Zhi ; 88(10): 697-700, 2008 Mar 11.
Artigo em Chinês | MEDLINE | ID: mdl-18642773

RESUMO

OBJECTIVE: To investigate the relationship of transforming growth factor beta1 (TGFbeta1) and basic fibroblast growth factor (bFGF) to detrusor underactivity following bladder outlet obstruction (BOO). METHODS: Female Wistar rats underwent ligation of the urethra to establish BOO models and were divided into BOO model 2-week group (11 rats) and BOO model 6-week group (10 rats). 8 rats underwent sham operation as control group. The detrusor urine was taken out and stimulated by carbachol to measure the detrusor contraction force (DCF). RT-PCR method was employed to measure the mRNA expression of TGFbeta1 and bFGF in the detrusor urine. Urine TGFbeta1 and bFGF were determined by ELISA. RESULTS: The maximum DCF levels of the BOO 2-week group under the 1 x 10(-4) mmol/L and 1 x 10(-3) mmol/L carbachol concentrations were 0.96 g +/- 0.11 g and 1.98 g +/- 0.21 g respectively, both significantly higher than those of the sham operation group (0.85 g +/- 0.18 g and 1.82 g +/- 0.19 g respectively, both P < 0.05). The maximum DCF levels of the BOO 6-week group under the 1 x 10(-5), 1 x 10(-4), 1 x 10(-3) and 1 x 10 (-2) mmol/L carbachol concentrations were 0.19 g +/- 0.02 g, 0.65 g +/- 0.06 g, 1.12 g +/- 0.08 g, and 1.40 g +/- 0.19 g respectively, all significantly lower than those of the BOO 2-week group (0.24 g +/- 0.03 g, 0.96 g +/- 0.11 g, 1.98 g +/- 0.21 g, and 2.16 g +/- 0.21 g respectively, all P < 0.05) and those of the sham operation group (0.23 g +/- 0.04 g, 0.85 g +/- 0.18 g, 1.82 g +/- 0.19 g, and 2.12 g +/- 0.26 g respectively, all P < 0.05). The mRNA expression of TGFbeta1 of the BOO 6-week group, BOO 2-week group, and sham operation group was 0.72 +/- 0.21, 0.34 +/- 0.10, and 0.32 +/- 0.01 respectively, there was a significant difference between the BOO 6-week group and the BOO 2-week group (P < 0.01). The mRNA expression level of bFGF of the BOO 6-week group was 0.38 +/- 0.13, significantly higher than those of the BOO 2-week group and sham operation group (0.21 +/- 0.07 and 0.10 +/- 0.05 respectively, both P <0.05). DCF was negatively correlated with the mNRA expression of TGFbeta1 and the mNRA expression bFGF in detrusor (both P < 0.05). The urine TGFbeta1 of the BOO 6-week group was (606 +/- 216) microg/mol Cr, significantly higher than that of the BOO 2-week group [(131 +/- 49) microg/mol Cr] and that of the sham operation group [(107 +/- 22) microg/mol Cr, both P <0.05]. CONCLUSION: With the progression of BOO, there is a sustained rise of bFGF mRNA expression in detrusor; however, the TGFbeta1 mRNA expression only increases during the decompensation stage. Urine TGFbeta1 level is very high 6 weeks after BOO, which may help predict the contraction function of bladder after BOO.


Assuntos
Fator 2 de Crescimento de Fibroblastos/genética , Fator de Crescimento Transformador beta1/genética , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Bexiga Urinária/metabolismo , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Fator 2 de Crescimento de Fibroblastos/urina , Expressão Gênica , Contração Muscular , Músculo Liso/metabolismo , Músculo Liso/patologia , Músculo Liso/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta1/urina , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Obstrução do Colo da Bexiga Urinária/urina
17.
J Pediatr Hematol Oncol ; 30(2): 179-81, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18376275

RESUMO

Infantile myofibromatosis is the most common fibrous tumor of infancy. Solitary or generalized myofibromas without visceral involvement usually regress within a few months. The multifocal disease infantile generalized myofibromatosis, with visceral involvement, is associated with a significant mortality due to the effect of tumors on vital organs. We report a case of infantile generalized myofibromatosis with visceral involvement, including 2 right atrium tumors. The infant expressed high circulating vascular endothelial growth factor and fibroblast growth factor-2 levels, and interferon alpha-2b was started as antiangiogenic treatment, aimed at triggering regression of the life-threatening cardiac lesions. The tumors regressed and vascular endothelial growth factor and fibroblast growth factor-2 levels were reduced after treatment discontinuation.


Assuntos
Interferon-alfa/uso terapêutico , Miofibromatose/tratamento farmacológico , Feminino , Fator 2 de Crescimento de Fibroblastos/sangue , Fator 2 de Crescimento de Fibroblastos/urina , Humanos , Lactente , Interferon alfa-2 , Proteínas Recombinantes , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/urina
18.
Cancer Chemother Pharmacol ; 63(1): 65-74, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18320191

RESUMO

PURPOSE: This study evaluated the safety, toxicity, pharmacological properties and biological activity of PI-88, a heparanase endoglycosidase enzyme inhibitor, with fixed weekly docetaxel in patients with advanced solid malignancies. EXPERIMENTAL DESIGN: This was a phase I study to determine the maximal-tolerated dose of escalating doses of PI-88 administered subcutaneously for 4 days per week, along with docetaxel 30 mg/m(2) given on days 1, 8, 15 of a 28-day schedule. RESULTS: Sixteen patients received a total of 42 courses of therapy. No dose-limiting toxicities were observed despite escalation to the highest planned dose level of PI-88 (250 mg/day). Frequent minor toxicities included fatigue (38%), dysgeusia (28.5%), thrombocytopenia (12%), diarrhea (14%), nausea (12%), and emesis (10%) in the 42 courses. No significant bleeding complications were observed. One patient developed a positive anti-heparin antibody test/serotonin releasing assay with positive anti-platelet factor 4/PI-88 antibodies and grade 1 thrombocytopenia in cycle 5, and was withdrawn from the study without any sequelae. PI-88 plasma concentrations (mirrored by APTT) and urinary elimination were linear and dose-proportional. Docetaxel did not alter the pharmacokinetic (PK) profile of PI-88, nor did PI-88 affect docetaxel PK. No significant relationship was determined between plasma or urine FGF-2, or plasma VEGF levels and PI-88 dose/response. Although no objective responses were observed; 9 of the 15 evaluable patients had stable disease for greater than two cycles of therapy. CONCLUSION: PI-88 administered at 250 mg/day for 4 days each week for 3 weeks with docetaxel 30 mg/m(2) on days 1, 8 and 15, every 28 days, was determined to be the recommended dose level for phase II evaluation. This combination was well tolerated without severe toxicities or PK interactions.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/imunologia , Inibidores da Angiogênese/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Docetaxel , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Fator 2 de Crescimento de Fibroblastos/urina , Gastroenteropatias/induzido quimicamente , Glucuronidase/antagonistas & inibidores , Heparina/imunologia , Humanos , Masculino , Concentração Máxima Permitida , Pessoa de Meia-Idade , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/terapia , Oligossacarídeos/administração & dosagem , Oligossacarídeos/efeitos adversos , Oligossacarídeos/imunologia , Oligossacarídeos/farmacocinética , Tempo de Tromboplastina Parcial , Fator Plaquetário 4/imunologia , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Taxoides/farmacocinética , Fator A de Crescimento do Endotélio Vascular/urina
19.
Zhonghua Wai Ke Za Zhi ; 44(3): 186-8, 2006 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-16635349

RESUMO

OBJECTIVE: To investigate a novel method to differentiate hemangioma from vascular malformation, to stage hemangiomas and to monitor the efficacy of management for hemangioma. METHODS: The urinary basic fibroblast growth factor (bFGF) concentration of 144 cases (including 69 cases of proliferating hemangiomas, 41 cases of involuting hemangiomas, 23 cases of vascular malformations and 11 negative controls) was examined using enzyme linked immunosorbent assay (ELISA). RESULTS: The differences of urinary bFGF concentration among proliferating hemangiomas, involuting hemangiomas, vascular malformations and negative control were all significant, while the differences between the latter three groups were not significant. CONCLUSIONS: Our findings suggest that examination of urinary bFGF concentration using ELISA technique is helpful in differentiating hemangioma from vascular malformation, staging hemangiomas and dynamically monitoring the efficacy of treatment for hemangiomas. Our results probably shed new light on the potential pathogenesis of hemangiomas and vascular malformation.


Assuntos
Malformações Arteriovenosas/diagnóstico , Fator 2 de Crescimento de Fibroblastos/urina , Hemangioma/diagnóstico , Malformações Arteriovenosas/urina , Pré-Escolar , Diagnóstico Diferencial , Hemangioma/urina , Humanos , Lactente , Recém-Nascido
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