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1.
Hematol Oncol ; 35(3): 365-373, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26999811

RESUMEN

The aim of this study was to evaluate the clinical significance of circulating tight junction (TJ) proteins as biomarkers reflecting of leukaemia central nervous system (CNS) metastasis. TJs [claudin5 (CLDN5), occludin (OCLN) and ZO-1] concentrations were measured in serum and cerebrospinal fluid (CSF) samples obtained from 45 leukaemia patients. Serum ZO-1 was significantly higher (p < 0.05), but CSF ZO-1 levels were not significantly higher in the CNS leukaemia (CNSL) compared to the non-CNSL. The CNSL patients also had a lower CLDN5/ZO1 ratio in both serum and CSF than in non-CNSL patients (p < 0.05). The TJ index was negatively associated with WBCCSF , ALBCSF and BBB values in leukaemia patients. Among all of the parameters studied, CLDN5CSF had the highest specificity in discriminating between CNSL and non-CNSL patients. Therefore, analysing serum and CSF levels of CLDN5, OCLN and the CLDN5/ZO1 ratio is valuable in evaluating the potential of leukaemia CNS metastasis. Copyright © 2016 John Wiley & Sons, Ltd.


Asunto(s)
Barrera Hematoencefálica/metabolismo , Neoplasias del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/secundario , Leucemia/patología , Proteínas de Uniones Estrechas/sangre , Adolescente , Adulto , Biomarcadores , Barrera Hematoencefálica/patología , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/mortalidad , Niño , Claudina-5/sangre , Claudina-5/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Ocludina/sangre , Ocludina/líquido cefalorraquídeo , Evaluación del Resultado de la Atención al Paciente , Pronóstico , Curva ROC , Proteínas de Uniones Estrechas/líquido cefalorraquídeo , Adulto Joven , Proteína de la Zonula Occludens-1/sangre , Proteína de la Zonula Occludens-1/líquido cefalorraquídeo
2.
J Neurooncol ; 122(2): 229-44, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25630624

RESUMEN

Metastasis to the central nervous system (CNS) is the primary obstacle in leukemia treatment. Matrix metalloproteinase-9 (MMP-9), chemokine ligand-2 (CCL2) and soluble vascular adhesion molecule-1 (sVCAM-1) play crucial roles in tumor cell adhesion, motivation and survival, but their roles in leukemia CNS metastasis remain to be elucidated. We investigated the prognostic significance of serum and cerebrospinal fluid (CSF) MMP-9, CCL2 and sVCAM-1 in leukemia patients to explore their potential as predictive biomarkers of the development of CNS leukemia (CNSL). MMP-9, CCL2 and sVCAM-1 were measured in paired CSF and serum samples collecting from 33 leukemia patients with or without CNS metastasis. Other risk factors related to CNSL prognosis were also analyzed. sVCAM-1Serum and CCL2Serum/CSF were significantly higher in the CNSL group than in the non-CNSL group and the controls (p < 0.05). MMP-9Serum was insignificantly lower in the CNSL group than in the non-CNSL group and the controls (p > 0.05). No differences were found for the sVCAM-1Serum, CCL2Serum, and MMP-9Serum levels between non-CNSL patients and controls (p > 0.05). MMP-9CSF was significantly higher in the CNSL group than both the non-CNSL and the control groups (p < 0.05). The indexes of sVCAM-1, CCL2, and MMP-9 in the CNSL group were lower than in the controls (p < 0.05). Positive correlations were determined between the MMP-9CSF and the ALBCSF/BBB value/WBCCSF, between sVCAM-1Serum and the WBCCSF/BBB value. Negative correlations existed between MMP-9Serum and the ALBCSF/BBB value/WBCCSF, and between the CCL2 index and ALBCSF. sVCAM-1Serum was positively associated with event-free survival (EFS), and patients with higher levels of ALBCSF, MMP-9CSF/Serum, CCL2CSF/Serum, and sVCAM-1CSF/Serum had shorter EFS. MMP-9CSF, CCL2CSF and sVCAM-1CSF are the first three principal components analyzed by cluster and principal component analysis. Our data suggest that MMP-9, CCL2 and sVCAM-1 in the CSF may be more potent than serum in predicting the possibility of leukemia metastatic CNS and the outcome of CNSL patients.


Asunto(s)
Neoplasias del Sistema Nervioso Central/sangre , Neoplasias del Sistema Nervioso Central/líquido cefalorraquídeo , Leucemia/patología , Adolescente , Adulto , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/líquido cefalorraquídeo , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/secundario , Quimiocina CCL2/sangre , Quimiocina CCL2/líquido cefalorraquídeo , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/líquido cefalorraquídeo , Análisis de Componente Principal , Pronóstico , Curva ROC , Factores de Riesgo , Sensibilidad y Especificidad , Molécula 1 de Adhesión Celular Vascular/sangre , Molécula 1 de Adhesión Celular Vascular/líquido cefalorraquídeo , Adulto Joven
3.
Diabetes Technol Ther ; 16(4): 224-34, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24279470

RESUMEN

BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in the pathogenesis of diabetic microvascular disease. Most diabetes patients have higher serum levels of ferritin that may participate in diabetic vascular complications through high oxidative stress induced by iron. However, the mechanistic link between ferritin and VEGF is obscure. The study investigated the association of VEGF and ferritin in patients with diabetic microvascular disease. PATIENTS AND METHODS: Sixty patients with type 2 diabetes mellitus (T2DM) and 26 healthy individuals were selected in this study. Serum ferritin, VEGF, hematological parameters, and clinical data were assessed in this cohort. The Spearman rank method was used to evaluate the associations among them. RESULTS: Serum levels of VEGF and ferritin were significantly higher in diabetes patients compared with the controls; levels of both were elevated with development of the disease. There were positive correlations between VEGF and glucose levels and between VEGF and ferritin in diabetes groups, especially in patients with diabetic retinopathy. Positive correlations were also found between VEGF level and the parameters of age, hemoglobin, and albumin in patients with diabetes hypertension. CONCLUSIONS: Our data suggest that high ferritin levels in T2DM are closely related to the development of diabetic vascular complications through interaction with VEGF.


Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Angiopatías Diabéticas/metabolismo , Ferritinas/metabolismo , Hiperglucemia/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Anciano , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Progresión de la Enfermedad , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hiperglucemia/fisiopatología , Hipertensión/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Microcirculación , Persona de Mediana Edad
4.
J Neurooncol ; 112(3): 329-38, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23400753

RESUMEN

Over-expression of vascular endothelial growth factor A (VEGF-A) is correlated with leukemia metastasis. VEGF-A acts by binding to its membrane receptors R1 and R2 present in soluble forms (sVEGFR1, sVEGFR2) with different functions. sVEGFR could inhibit VEGF-A bioactivities, associated with favorable prognosis in solid tumors. However, its role is obscure in central nervous system leukemia (CNSL). The aim of this study was to investigate sVEGFR1, R2 as biomarkers in CNSL. Paired cerebrospinal fluid (CSF) and serum samples were collected from 35 leukemia cases with or without CNS metastasis. Levels of sVEGFR1 and sVEGFR2 in both CSF (sVEGFR1CSF, sVEGFR2CSF) and serum (sVEGFR1Serum, sVEGFR2Serum) were detected by ELISA. Other risk factors related to CNSL prognosis were also analyzed. sVEGFRSerum levels were 2.54-fold (sVEGFR1) and 25.6-fold (sVEGFR2) higher than sVEGFRCSF in both leukemic groups. sVEGFR1CSF in CNSL were 33 % higher than in the non-CNSL, and the levels of sVEGFR2CSF and sVEGFR2Serum had the same trend. Elevated sVEGFR1CSF and sVEGFR2CSF is closely correlated with blood-brain barrier (BBB) values and WBCCSF that is an indicator of CNSL disease burden. Cox regression analysis showed that the sVEGFR2CSF had a positive effect on event-free survival. Our data suggest that sVEGFR2CSF may be more potent than sVEGFR1CSF in predicting the outcome of leukemia patients, the balance between sVEGFR2CSF and VEGF-ACSF levels might be crucial for the progression of CNSL.


Asunto(s)
Biomarcadores de Tumor/líquido cefalorraquídeo , Neoplasias del Sistema Nervioso Central/líquido cefalorraquídeo , Leucemia/líquido cefalorraquídeo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Adolescente , Adulto , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/patología , Niño , Preescolar , Supervivencia sin Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Estimación de Kaplan-Meier , Leucemia/mortalidad , Leucemia/patología , Masculino , Pronóstico , Adulto Joven
5.
Leuk Res ; 37(4): 359-66, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23137522

RESUMEN

Metastasis to the central nervous system (CNS) is an obstacle for leukemia treatment, the mechanisms of which remain to be elucidated. VEGF-A and VEGF-C are suspected to participate in this process. Paired of cerebrospinal fluid (CSF) and serum samples were collected from leukemia and control cases. Levels of VEGF-A and VEGF-C in both CSF (VEGF-ACSF, VEGF-CCSF) and serum (VEGF-ASerum, VEGF-CSerum) were detected by ELISA. Our data show that higher levels of VEGF-ACSF are closely related to CNS leukemia (CNSL), and VEGF-ACSF may be a better predictor than the other risk factors elucidating the pathogenesis and development of CNSL.


Asunto(s)
Neoplasias del Sistema Nervioso Central/secundario , Neoplasias/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor C de Crecimiento Endotelial Vascular/metabolismo , Adolescente , Adulto , Barrera Hematoencefálica , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Adulto Joven
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