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1.
Klin Lab Diagn ; 64(10): 588-593, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31742950

RESUMO

At some works, it has been shown there are signs of damage and endothelium dysfunction in patients with chronic viral hepatitis (CVH) and liver cirrhosis of viral etiology the severity of these conditions depends on the severity of the pathological process. Evaluation of the role of angiogenic factors and endothelial dysfunction in persistent of CVH in children and adolescents. 35 patients were examined: of which 11 with chronic hepatitis B (CHB) and 24 with chronic hepatitis C (CHC). The reference group consisted of 120 practically healthy persons of the corresponding age and sex. VEGF-A, angiotensin (ANG), soluble receptors of VEGF-A (sVEGF-R1 и sVEGF-R2) and trombomodulin (TM) have been investigated in serum by enzyme immunoassay using special kits (BCM Diagnostics, USA). Other endothelial dysfunction markers as von Willebrand factor (vWf) was determined in blood plasma by immunoturbidimetry (Siemens, Germany), plasminogen (PLG) was investigated due to extended coagulation. In children with CVH, regardless of etiology, the concentration of VEGF-A was significantly lower, and sVEGF-R2, sVEGF-R1 and TM was higher than in children without liver disease (p <0.001, p <0.05, p <0.01, p <0.001, respectively). The concentration of TM and the level of PLG activity in patients with CHC were slightly higher than in CHB. Decreased level of VEGF-A and increased expression of its soluble receptors indicate enhanced inhibition of angiogenesis in CVH, which may indicate the pathogenetic role of this phenomenon in the development of liver damage in CHC.


Assuntos
Hepatite B Crônica/sangue , Hepatite C Crônica/sangue , Cirrose Hepática/virologia , Neovascularização Patológica/sangue , Adolescente , Angiotensinas/sangue , Biomarcadores/sangue , Criança , Humanos , Plasminogênio/análise , Trombomodulina/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue , Fator de von Willebrand/análise
2.
Anticancer Res ; 39(11): 6403-6412, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704874

RESUMO

BACKGROUND: Cytokines, metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) take part in many processes involved in tumor progression and invasion such as degradation of the extracellular matrix, influence on immune cells associated with tumor tissue, and angiogenesis. Thus, the aim of this study was to compare the concentration of plasma levels and tissue expression of macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2 and MMP9, and their tissue inhibitors TIMP1 and TIMP2 in patients with cervical cancer, patients with high-grade cervical intraepithelial dysplasia (CIN3) and patients with ectropion. PATIENTS AND METHODS: Concentration and expression of all tested parameters was measured in serum with enzyme-linked immunosorbent assay (ELISA) and in tissue with immunohistochemistry method. RESULTS: The epithelial expression of M-CSF and TIMP1 in cancer tissue was much stronger as compared to that in ectropion and CIN3. In the case of MMP2, lack of or weak expression in epithelial cells was observed in all tested groups. Our studies showed statistical differences of tested parameters in tissue expression and in plasma concentrations in patients with cervical cancer, patients with CIN3 and patients with ectropion. Moreover, data revealed positive correlation between plasma level and cervical cancer cell expression of VEGF. CONCLUSION: Our findings indicate a potential role of all the proteins tested here in cervical cancer diagnosis, especially VEGF. However, further studies will show whether they play a role in the progression of cancerous changes in epithelial tissue of the cervix.


Assuntos
Fator Estimulador de Colônias de Macrófagos/análise , Metaloproteases/análise , Inibidores Teciduais de Metaloproteinases/análise , Displasia do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/química , Fator A de Crescimento do Endotélio Vascular/análise , Adenocarcinoma/sangue , Adenocarcinoma/química , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/química , Citocinas/análise , Citocinas/sangue , Feminino , Humanos , Fator Estimulador de Colônias de Macrófagos/sangue , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/sangue , Metaloproteases/sangue , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/sangue , Inibidores Teciduais de Metaloproteinases/sangue , Displasia do Colo do Útero/sangue , Neoplasias do Colo do Útero/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
3.
Zhonghua Fu Chan Ke Za Zhi ; 54(9): 601-607, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31550776

RESUMO

Objective: To explore the pathways of preeclampsia by investigating different effects of pravastatin (Pra) on and soluble FMS tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) in different preeclampsia (PE)-like mouse models. Methods: C57BL/6J mice were randomly subcutaneously injected with N-nitro-L-arginine methyl ester (L-NAME) or intraperitoneally injected with lipopolysaccharide (LPS) as PE-like mouse model, saline as normal pregnancy control (Con) respectively, daily at gestational 7-18 days. Pra was given daily at gestational 8-18 days in each model group and the mice were divided into Pra (L-NAME+Pra, LPS+Pra, Con+Pra) and saline (L-NAME+NS, LPS+NS, Con+NS) groups. Liver,placental tissue and blood of pregnant mice were collected on the 18th day of pregnancy. The levels of VEGF, PlGF and sFlt-1 in the liver, placenta and serum of mice in each group were compared by western blot, ELISA and real-time fluorescence quantitative PCR (RT-PCR). Results: (1) ELISA: Serum VEGF (205.70±3.43, 154.60±2.31) and PlGF (131.5±3.75, 101.50±4.31) levels were significantly increased in L-NAME+Pra group compared with L-NAME+NS group (all P<0.05). Serum VEGF (202.30±4.90, 144.50±6.71) and PlGF (121.50±3.86, 95.41±4.08) levels were significantly higher in LPS+Pra group than those in LPS+NS group (all P<0.05). Serum sFlt-1 level in LPS+Pra group was significantly lower than that in LPS+NS group (3.01±0.50, 776.60±80.06), serum sFlt-1 level in L-NAME+Pra group was significantly lower than that in L-NAME+NS group (2.60±0.06, 583.70±9.83; all P<0.05). (2) Western blot: the expression levels of PlGF (1.344±0.118, 0.664±0.143) and VEGF (1.34±0.12, 0.66±0.14) in the liver of mice in the L-NAME+Pra group were significantly higher than those in the L-NAME+NS group (all P<0.05), but the expression levels of PlGF and VEGF in the placenta of L-NAME+Pra group were not significantly different from those of L-NAME+NS group (all P>0.05). The expression levels of PlGF and VEGF in placenta and liver of pregnant mice in LPS+Pra group were not significantly different from those in LPS+N group (all P>0.05). (3) RT-PCR: the mRNA expression of PlGF and VEGF in placenta and liver of L-NAME+Pra group were not significantly different from those in L-NAME+NS group (all P>0.05). The mRNA expression levels of PlGF and VEGF in placenta and liver of LPS+Pra group were not significantly different from those of LPS+NS group (all P>0.05). Conclusions: Pra has different regulatory effects on vascular endothelial function in different PE-like models. It reveals that different pathogenesis and pathways exist in different PE-like changes.


Assuntos
Fator de Crescimento Placentário/efeitos dos fármacos , Pravastatina/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Proteínas Recombinantes de Fusão/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Animais , Anticolesterolemiantes/farmacologia , Biomarcadores/sangue , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Placenta , Fator de Crescimento Placentário/sangue , Reação em Cadeia da Polimerase , Pravastatina/farmacologia , Pré-Eclâmpsia/sangue , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes de Fusão/sangue , Fator A de Crescimento do Endotélio Vascular/sangue
4.
Georgian Med News ; (291): 13-19, 2019 Jun.
Artigo em Russo | MEDLINE | ID: mdl-31418723

RESUMO

The aim of the study was the analysis of serum VEGF level in patients with varicose veins before and after the endovenous laser ablation (EVLA) and to study the role of VEGF in recurrence of the disease. The research involved 216 persons. The study group included 136 patients with varicose veins. Control group included 80 healthy persons. All 136 persons were treated by endovenous laser ablation. To establish the presence of recurrent veins we conducted several observations of patients in period of 1/2-1-3-6-12 months after the treatment and then every 6 month during 3 years. Serum samples were collected from patients' before the operation and 3-6 month after the operation. Serum VEGF level were significantly higher in study group (86,63 pg/ml) comparing to control group 24.10 pg/ml (р 0,01). Mean level of VEGF before the operation were 86.83 pg/ml and in 3 month after the operation decreased to 24.98 pg/ml (р=0,01). In recurrent cases VEGF level were 3 times higher than in non-recurrent cases (р=0,01). There is a direct correlation of VEGF level and recurrence r=0,40, also direct correlation established between the СЕАР clinical class and VEGF level r=0,64.


Assuntos
Terapia a Laser , Varizes/sangue , Varizes/terapia , Fator A de Crescimento do Endotélio Vascular/sangue , Humanos , Recidiva , Resultado do Tratamento
5.
Adv Clin Exp Med ; 28(10): 1301-1309, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31430066

RESUMO

BACKGROUND: Non-healing wounds are becoming a growing concern for public health as a result of their increasing prevalence in progressively aging societies. OBJECTIVES: The aim of this article is to evaluate the effects of wound etiology on a panel of circulating cytokines in patients with non-healing wounds of the lower extremities. MATERIAL AND METHODS: This prospective case-control study involved 104 individuals: healthy elderly people (n = 46) and patients with diabetes and/or cardiovascular disease (n = 58; among them 38 with chronic wounds of venous, ischemic or neurotrophic etiology). Selected serum cytokines - i.e. IL-1ß, IL-4, IL-6, IL-8, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α, TNF-α, VEGF-A, and PDGF-BB - were measured using the Luminex platform. RESULTS: Compared to healthy elderly people, presence of diabetes and/or cardiovascular disease was associated with elevated IL-6, IL-8, MCP-1 and G-CSF while non-healing wounds coexisted with the increase in the levels of all examined cytokines/growth factors except for G-CSF and GM-CSF. Among diseased elderly people, having wounds was associated with increased levels of IL-1ß, IL-4, IL-6, IL-8, FGF-2, MIP-1α, PDGF-BB, and VEGF-A. Interleukin 1ß elevation was a sole independent predictor of chronic wounds with an odds ratio (OR) of 6.3. Cytokines in healthy seniors were loosely interrelated, while the levels of cytokines in diseased patients with wounds displayed a tight pattern of association. When stratified by their etiology, the association pattern for IL-6, IL-8, MCP-1, and VEGF-A was disrupted in neurotrophic wounds. CONCLUSIONS: The results presented herein may improve our understanding of the pathomechanisms which lead to chronic wounds and of the effects they exert on a systemic level, as well as providing potential targets for more effective therapies.


Assuntos
Biomarcadores/análise , Quimiocinas/sangue , Citocinas/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Cicatrização/fisiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Crônica , Citocinas/metabolismo , Feminino , Humanos , Inflamação/sangue , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
An Bras Dermatol ; 94(3): 320-326, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365661

RESUMO

BACKGROUND: Behçet's disease is a multisystemic vasculitis, associated with vascular endothelial dysfunction. Currently, the prognosis is unpredictable, because there is still no valid laboratory marker indicating the disease activity in Behçet's disease. Endothelial progenitor cells and circulating endothelial cells are newly introduced hematological markers which are presumed to take part in the pathogenesis of vasculitis. OBJECTIVES: To evaluate the levels of endothelial progenitor cells and subtypes and circulating endothelial cells in patients with Behçet's disease and to describe their relationship with the disease activity. METHODS: A total of 45 patients with Behçet's disease and 28 healthy controls were included in the study. Endothelial progenitor cells (CD34+CD133+KDR+ as early endothelial progenitor cells and CD34+KDR+ as late endothelial progenitor cells), and circulating endothelial cells (CD34+CD133+) were measured by flow cytometry. RESULTS: The mean plasma level of endothelial progenitor cells and circulating endothelial cells, vascular endothelial growth factor, matrix metalloproteinase-9, C-reactive protein, and erythrocyte sedimentation rate were significantly higher in patients with Behçet's disease. All of these parameters except circulating endothelial cells were also found to be higher in patients with active disease than in patients with inactive disease. Early endothelial progenitor cells showed significant correlations with C-reactive protein and circulating endothelial cells. STUDY LIMITATIONS: The cross-sectional nature of the study and patient characteristics such as being under treatment, which can affect endothelial progenitor cells numbers. CONCLUSION: The increase in endothelial progenitor cells may play an essential role in the repair of endothelial injury in Behçet's disease, especially in the active period of the disease. Thus, endothelial progenitor cells can indicate the disease activity. In addition, endothelial progenitor cells and circulating endothelial cells can be used as endothelial repair and injury markers for Behçet's disease, respectively.


Assuntos
Síndrome de Behçet/sangue , Biomarcadores/sangue , Células Progenitoras Endoteliais/metabolismo , Adulto , Síndrome de Behçet/complicações , Proteína C-Reativa/análise , Estudos de Casos e Controles , Contagem de Células , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/sangue , Vasculite
7.
Nord J Psychiatry ; 73(4-5): 302-307, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31170860

RESUMO

Background and aim: Recent evidence suggests that growth factors might be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The aim of this study was to determine whether serum levels of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), nerve growth factor (NGF), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) were altered in children with ADHD. Methods: Serum levels of BDNF, GDNF, NT-3, NGF, VEGF and FGF-2 were analyzed in 49 treatment- naive children with ADHD and age, gender matched 36 healthy controls using enzyme-linked immunosorbent assay. ADHD symptoms were scored by Du Paul ADHD Rating Scale and Strengths and Difficulties Questionnaire. Results: We found that serum VEGF levels were significantly lower (p < 0.001) and GDNF levels were significantly higher in ADHD group compared to control group (p = 0.003). However, we found no correlations between ADHD symptoms and serum VEGF or GDNF levels. Furthermore, we observed no significant alterations in serum BDNF, NT-3, NGF, FGF-2 levels in children with ADHD. Conclusion: To our knowledge, the present study is the first to examine serum VEGF and FGF-2 levels in children with ADHD. Our results indicate that VEGF and GDNF might be involved in the etiology of ADHD. Further studies are required to determine the role of growth factors in the etiology and consequently in the treatment of ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/sangue , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Fator 2 de Crescimento de Fibroblastos/sangue , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Biomarcadores/sangue , Criança , Feminino , Humanos , Masculino
8.
J Biol Regul Homeost Agents ; 33(2 Suppl. 1): 39-43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31169001

RESUMO

With the advent of the molecularly targeted therapies, identifying molecular therapeutic targets and molecolar marker is increasingly important, especially in neoplastic diseases. Several studies show VEGF is involved in neo-angiogenesis in many solid cancers, as breast, lung, renal, gastric carcinomas, through promoting endothelial cell growth and migration. Conversely the relationship between VEFG and tumours of the musculoskeletal system is yet unclear, in particular the role of VEGF has not yet been completely understood in these tumours. Chondrosarcoma, Ewing's Sarcoma and Osteosarcoma are the tumours of the musculoskeletal system in which the activity of VEGF has been closely studied. The present study aims to give an overview focused on the relationship between VEGF and these three cancers.


Assuntos
Neoplasias Ósseas/diagnóstico , Condrossarcoma/diagnóstico , Osteossarcoma/diagnóstico , Sarcoma de Ewing/diagnóstico , Fator A de Crescimento do Endotélio Vascular/sangue , Biomarcadores Tumorais/sangue , Humanos , Prognóstico
9.
Int J Sports Med ; 40(7): 440-446, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31189189

RESUMO

This study aimed to evaluate the influence of physical activity on incidence of acute mountain sickness (AMS) by continuous activity monitoring in a free-living sample of South Pole workers over the initial 72 h at altitude exposure of 2,840 m (9,318 ft). Body Media activity monitors were worn by 47 healthy participants. AMS was defined by the Lake Louise symptom questionnaire. Venous blood samples were taken at sea level and approximately 48 h after high altitude exposure. AMS incidence was 34% (n=16/47) over the first 48 h and 40% (n=19/47) over 72 h. On day 2 at high altitude, individuals with AMS demonstrated a significantly greater increase in the percent change in physical activity metrics from baseline: total energy expenditure 19±13 vs. 5±7%, total steps 65±51 vs. 10±18%, metabolic equivalent of tasks 21±13 vs. 7±13%, and time spent performing moderate to vigorous physical activity 114±79 vs. 26±27% for individuals with AMS vs. no AMS, respectively, p<0.05. In addition, erythropoietin and vascular endothelial growth factor were 1.69 and 1.75 times higher, respectively, in those with AMS. In conclusion, workers who engaged in increased physical activity and activity intensity during initial exposure to the South Pole were more susceptible to developing AMS.


Assuntos
Doença da Altitude/fisiopatologia , Exercício , Esforço Físico , Doença da Altitude/sangue , Doença da Altitude/epidemiologia , Regiões Antárticas/epidemiologia , Metabolismo Energético , Eritropoetina/sangue , Monitores de Aptidão Física , Humanos , Incidência , Fatores de Risco , Fator A de Crescimento do Endotélio Vascular/sangue
10.
BMC Cancer ; 19(1): 427, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068179

RESUMO

BACKGROUND: Several studies have documented that blood biomarkers can improve basic prognostic models in radiotherapy and radio-chemotherapy for non-small cell lung cancer. The current study evaluated the prognostic impact of six markers focusing on their utility in homogenous subsets, compared to the significance in a large heterogeneous group. METHODS: Blood samples of 337 patients who were referred for curative or palliative external beam thoracic radiotherapy for non-small cell lung cancer were collected. The concentration of osteopontin (OPN), vascular endothelial growth factor (VEGF), erythropoetin (EPO), high mobility group box 1 protein (HMGB1), insulin-like growth factor 1 (IGF-1) and platelet-derived growth factor (PDGF) in serum were measured by ELISA assay and the prognostic potential was assessed using univariable and multivariable survival models. RESULTS: Multivariable analysis revealed that out of several variables studied six dichotomized features: namely: cigarette smoking, lack of chemotherapy, palliative doses of radiotherapy, high OPN concentration, advanced T stage and high VEGF concentration had a highly significant (p < 0.005) and independent influence on overall survival in the group of 337 patients. In a subset of patients treated with curative radio-chemotherapy or radiotherapy (N = 148) tumor pathology, EPO concentration and VEGF concentration, significantly and independently influenced overall survival. In a subset of patients with squamous cell cancer (N = 206) OPN had a highly significant impact on overall survival. In contrast, in a subset of patients with nonsquamous histology (N = 131) only VEGF had a significant influence on survival. CONCLUSIONS: Blood serum proteins appear to be clinically useful prognosticators of overall survival in radio-chemotherapy and radiotherapy for non-small cell lung cancer. In unselected heterogeneous groups, dichotomized concentrations of OPN and VEGF emerged among the strongest independent prognosticators of overall survival. VEGF and EPO concentration (dichotomized) were found to be independent prognostic factors among the patients treated with curative doses of radiotherapy. The utility of OPN as a prognostic marker appeared restricted to the patients with squamous histology.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Eritropoetina/sangue , Feminino , Seguimentos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Osteopontina/sangue , Prognóstico , Estudos Prospectivos , Medição de Risco/métodos , Análise de Sobrevida , Fator A de Crescimento do Endotélio Vascular/sangue
11.
Zhongguo Zhong Yao Za Zhi ; 44(8): 1696-1703, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31090337

RESUMO

To study the effect of modified Buyang Huanwu Decoction on the hemorrhagic transformation after intravenous thrombolysis of recombinant tissue type plasminogen activator(rt-PA) in patients with super early(onset time<4. 5 h) cerebral infarction. From March 2016 to July 2018,at the brain disease zone of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,212 cases of super early cerebral infarction were selected and divided into two group according to the randomized complete blocks designs: control group(106 cases) and traditional Chinese medicine group(106 cases). The control group was treated with rt-PA intravenous thrombolysis,while the traditional Chinese medicine group was treated with modified Buyang Huanwu Decoction in addition to the therapy of the control group. Both groups were treated for 14 days. Neurological deficit score,serum matrix metalloproteinase-9(MMP-9),neuron specific enolase(NSE),vascular endothelial growth factor(VEGF) and plasma cellular fibronectin(c-FN) levels,the incidence of hemorrhagic transformation,clinical efficacy and adverse drug reactions before and after treatment were compared between the two groups. According to the findings,at the 14 thday after treatment,the rank sum test of the grade data showed that the clinical efficacy of the traditional Chinese medicine group was better than that of the control group(Z =-2. 033,P = 0. 042); on the basis of χ2 test,the total efficiency of the traditional Chinese medicine group was higher than that of the control group(χ2= 4. 895,P =0. 027); the hemorrhagic transformation rate of the traditional Chinese medicine group was lower than that of the control group within14 days of treatment(χ2= 3. 962,P = 0. 047). MMP-9 levels in the traditional Chinese medicine group were lower than those in the control group at the 3 rd,5 th,7 th,10 th,14 thd after treatment(t =-2. 474,-3. 022,-5. 163,-6. 998,-9. 821; P = 0. 014,0. 003,0,0,0). The improvement of c-FN,NSE,VEGF and NIHSS scores in the traditional Chinese medicine group was superior to that of the control group after 14 days of treatment(t =-2. 343,-3. 187,-2. 129,-3. 105; P = 0. 020,0. 002,0. 034,0. 002). No obvious adverse reactions of modified Buyang Huanwu Decoction were observed during 14 days of treatment. Modified Buyang Huanwu Decoction could reduce the expressions of MMP-9,c-FN,NSE and VEGF after rt-PA intravenous thrombolysis in patients with super early cerebral infarction,and decrease the hemorrhagic transformation rate after thrombolysis,with high safety.


Assuntos
Infarto Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Ativador de Plasminogênio Tecidual/uso terapêutico , Fibronectinas/sangue , Humanos , Metaloproteinase 9 da Matriz/sangue , Medicina Tradicional Chinesa , Fosfopiruvato Hidratase/sangue , Proteínas Recombinantes/uso terapêutico , Terapia Trombolítica , Fator A de Crescimento do Endotélio Vascular/sangue
12.
BMC Cancer ; 19(1): 398, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035945

RESUMO

BACKGROUND: The search of useful serum biomarkers for the early detection of cervical cancers has been of a high priority. The activation of Macrophage-Colony Stimulating Factor (M-CSF) and Vascular Endothelial Growth Factor (VEGF) is likely involved in the pathogenesis and spread of cancer. We compared the plasma levels of M-CSF and VEGF to the ones of commonly accepted tumor markers CA 125and SCC-Ag in three groups of patients: 1. the cervical cancer group (patients with either squamous cell carcinoma or adenocarcinoma); 2. the cervical dysplasia group; 3. the control group. METHODS: This cohort study included 100 patients with cervical cancer and 55 patients with cervical dysplasia. The control group consisted of 50 healthy volunteers. The plasma levels of VEGF and M-CSF were determined using ELISA, while CA 125 and SCC-Ag concentrations were obtained by the chemiluminescent microparticle immunoassay (CMIA). RESULTS: The median levels of M-CSF and VEGF as well as CA 125 and SCC-Ag in the entire group of cervical cancer patients, were significantly different compared to the healthy women group. In case of both the squamous cell carcinoma and the adenocarcinoma groups, plasma levels of M-CSF and VEGF were higher compared to the control group. No significant differences in the studied parameters between the squamous cell carcinoma and the adenocarcinoma group were observed. The highest sensitivity and specificity were obtained for VEGF (81.18 and 76.00%, respectively) and SCC-Ag (81.18%; 74.00%) in the squamous cell carcinoma group and for VEGF (86.67%; 76.00%) in the adenocarcinoma group. The area under the ROC curve for VEGF was the largest in the adenocarcinoma group followed by the squamous cell carcinoma group (0.9082 and 0.8566 respectively). CONCLUSIONS: Obtained results indicate a possible clinical applicability and a high diagnostic power for the combination of MSC-F, VEGF, CA 125 and SCC-Ag in the diagnosis of both studied types of cervical cancer.


Assuntos
Biomarcadores Tumorais/sangue , Fator Estimulador de Colônias de Macrófagos/sangue , Neoplasias do Colo do Útero/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico , Adulto , Antígenos de Neoplasias/sangue , Antígeno Ca-125/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Curva ROC , Serpinas/sangue , Displasia do Colo do Útero/sangue , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto Jovem
13.
Rinsho Ketsueki ; 60(4): 308-313, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31068561

RESUMO

We report three cases of POEMS syndrome treated with lenalidomide and dexamethasone who presented with peripheral neuropathy. All of them had markedly elevated serum vascular endothelial growth factor (VEGF) levels treated with lenalidomide and dexamethasone for severe peripheral neuropathy, which normalized serum VEGF levels and improved peripheral neuropathy. The standard treatment of POEMS syndrome has not been established, but has been effectively treated with high-dose chemotherapy with autologous stem cell transplantation. Newer agents currently used for plasma cell dyscrasias include bortezomib and immunomodulatory drugs, such as thalidomide and lenalidomide. A randomized controlled trial on thalidomide plus dexamethasone for POEMS syndrome showed reduced serum VEGF levels after therapy; however, the incidence of peripheral neuropathy, a well-known side effect of both thalidomide and bortezomib, increased. Lenalidomide is associated with lower incidence of peripheral neuropathy compared to thalidomide and bortezomib, making it a reasonable treatment option for POEMS syndrome.


Assuntos
Dexametasona/uso terapêutico , Lenalidomida/uso terapêutico , Síndrome POEMS/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante Autólogo , Fator A de Crescimento do Endotélio Vascular/sangue
14.
Ann Hematol ; 98(7): 1721-1732, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055613

RESUMO

The CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has been widely proved effective on relapsed and refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL). Meanwhile, CAR-T therapy-related toxicities, including cytokine release syndrome (CRS) and neurological toxicities, are drawing researchers' attention. In addition, our research team notices that coagulopathy and even disseminated intravascular coagulation (DIC) are common problems during CAR-T therapy. In our phase 1/2 clinical trial (NCT02965092), 53 r/r B-ALL patients underwent leukapheresis on day - 11 and received lymphodepleting chemotherapy on day - 7 to day - 5. Finally, they received split infusions of anti-CD19 CAR-T cells on day 0 to day 2. Plasma concentrations of tissue factor (TF) and platelet endothelial cell adhesion molecular-1 (PECAM-1) were also measured to identify the mechanism of coagulation disorders. The overall 1-month remission rate of the 53 patients was 88.7%. During the treatment course, 19 patients experienced grade 3-4 CRS, 8 patients developed grade 2-3 neurological toxicities. Beyond that, 30 patients (30/53, 56.6%) suffered from coagulation disorders, and half of them should be diagnosed as DIC. Benefiting from replacement and anticoagulant therapy, 14 patients successfully got out of the conditions of DIC. Remarkably, the severity of coagulopathy was positively correlated with CRS grade. What is more, plasma TF and PECAM-1 levels indicated that vascular endothelial factors played key roles in the process of CRS-related coagulopathy. To conclude, coagulation disorders frequently happen during CAR-T therapy. TF and PECAM-1 are of great importance in the etiology and pathogenesis of coagulation problems. Early and proper interventions targeted at CRS-related coagulopathy contribute a lot to the control of side effects in CAR-T therapy.


Assuntos
Coagulação Intravascular Disseminada , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Segurança , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Intervalo Livre de Doença , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/mortalidade , Coagulação Intravascular Disseminada/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Molécula-1 de Adesão Celular Endotelial a Plaquetas/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras B/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Taxa de Sobrevida , Tromboplastina/metabolismo , Fator A de Crescimento do Endotélio Vascular/sangue
15.
Dis Markers ; 2019: 9401628, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019585

RESUMO

Background: Investigations regarding serum and plasma vascular endothelial growth factor (VEGF) levels in patients with diabetic retinopathy (DR) are conflicting. This meta-analysis is aimed at determining whether serum and plasma VEGF levels are associated with DR and its severity in diabetic patients. Methods: PubMed and EMBASE were used to search for published studies, and serum and plasma VEGF levels were compared among DR, nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and nondiabetic retinopathy (NDR) patients. Standardized mean differences (SMD) and 95% confidence interval (CI) were pooled using a random effects model. Results: A total of 29 studies comprising 1805 DR (or NPDR or PDR) patients and 1699 NDR patients were included. ELISA was used to evaluate serum or plasma VEGF levels in all except for two studies included in this meta-analysis. Overall, serum VEGF levels were significantly higher in DR patients (SMD: 0.74, 95% CI: 0.44-1.03) than those in NDR patients, while plasma VEGF levels were not in the comparison (SMD: 0.40, 95% CI: -0.13-0.92). Similarly, NPDR (SMD: 0.51, 95% CI: 0.22-0.80) and PDR (SMD: 1.32, 95% CI: 0.79-1.85) patients had higher serum VEGF levels compared with NDR patients, but the difference was not significant in plasma samples (SMD: 0.24, 95% CI: -0.47-0.95; SMD: 0.37, 95% CI: -0.30-1.05). In addition, serum VEGF levels were higher in PDR patients than those in NPDR patients (SMD: 0.87, 95% CI: 0.41-1.33), but plasma VEGF levels were not (SMD: -0.00, 95% CI: -0.31-0.31). The subgroup and metaregression analysis revealed that the study location, study design, and publication year of a study have certain influence on heterogeneity between studies in serum or plasma samples. Conclusions: VEGF levels in the serum instead of those in the plasma correlate to the presence and severity of DR in diabetic patients. Further large-scale studies are required to confirm these findings.


Assuntos
Retinopatia Diabética/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Pak J Biol Sci ; 22(3): 148-153, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30972985

RESUMO

BACKGROUND AND OBJECTIVE: Preeclampsia(PE) is adisordercharacterized byhypertensionandproteinuria. There is accumulating evidence that this is a disease of the endothelium. Angiogenic factors may be responsible for the regulation of placental vascular development. Clinicians cannot predict pre-eclampsia prior to the onset symptoms. An ideal bio-marker for pre-eclampsia prediction is during the first trimester. This study investigated the serum levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and the gene expressions of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) and p53 in PE trying to find out potential bio-markers for prediction and diagnosis of PE. MATERIAL AND METHODS: A total of 100 female volunteers were involved in this study and their ages were ranged from 25-35 years. They were divided into three groups: Group (1) was 20 healthy non-pregnant women, group (2) was 20 pregnant women normal pregnancies and group (3) was 60 preeclamptic patients. The study participants were enrolled at the Department of Obstetrics and Gynaecology at Mansoura University Hospital, Mansoura, Egypt. The study was approved by the Research Ethics Committee (Faculty of Science, Al Azhar University, Egypt) approved on the March 15, 2014) all women gave written informed consent. Serum levels of CRP, IL-10 and TNF-α were evaluated, in addition to the gene expression of VEGF, eNOS and p53. RESULTS: Significant elevations in the serum levels of blood pressure, TNF-α and CRP were observed in PE patients. Additionally, the gene expression of VEGF, eNOS and P53 were down-regulated in preeclampsia. CONCLUSION: Elevated serum levels of TNFα and CRP, in addition to the down-regulation of eNOS may be used as good predictors for preeclampsia. The TNF-α and VEGF gene were recommended used as markers for PE to be added to routine testes of pregnant women.


Assuntos
Citocinas/sangue , Perfilação da Expressão Gênica , Pré-Eclâmpsia/sangue , Complicações na Gravidez/sangue , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Egito , Feminino , Humanos , Interleucina-10/sangue , Óxido Nítrico Sintase Tipo III/sangue , Pré-Eclâmpsia/diagnóstico , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/sangue , Proteína Supressora de Tumor p53/sangue , Fator A de Crescimento do Endotélio Vascular/sangue
17.
Ophthalmic Res ; 62(2): 80-92, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31018207

RESUMO

This study aimed to evaluate the therapeutic effect of folic acid (FA) on diabetic retinopathy (DR) in a genetic mouse model of obese type 2 diabetes mellitus (T2D). C57BL/KsJ-db/db (db/db) T2D mice were divided into control, FA, metformin (MET), and FA plus MET groups (n = 10/group). Serum levels of glucose, glycated hemoglobin, and insulin were determined weekly. The retinal thickness was measured using optical coherence tomography (OCT) at 4 weeks after treatments. The retinal expression and serum levels of vascular formation, inflammation, and oxidative stress-associated molecules were examined. Our results demonstrated that FA, but not MET, played a protective role against retinal thinning in the early stage of DR in db/db mice, although FA did not exhibit antihyperglycemic effect. In addition, retinal expression and serum levels of a panel of molecules associated with angiogenesis (CD31 and VEGFR), inflammation (IL-1ß and NLRP3), and oxidative stress (3-NT, 4-HNE, Vav2, and NOX4) were significantly downregulated in FA-treated diabetic mice compared with those in saline-treated controls. Furthermore, the serum level of homocysteine was also markedly decreased following FA treatments. These findings suggest that through potential suppressions on angiogenesis, inflammation, and oxidative stress, FA may serve as a potential therapeutic agent against DR.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Ácido Fólico , Inflamação/metabolismo , Neovascularização Patológica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Retina , Análise de Variância , Animais , Biomarcadores/metabolismo , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Modelos Animais de Doenças , Feminino , Ácido Fólico/farmacologia , Ácido Fólico/uso terapêutico , Hemoglobina A Glicada/análise , Insulina/sangue , Interleucina-1beta/sangue , Camundongos , Camundongos Endogâmicos C57BL , Retina/metabolismo , Retina/patologia , Fator A de Crescimento do Endotélio Vascular/sangue
18.
BMC Cancer ; 19(1): 292, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935424

RESUMO

BACKGROUND: Although sorafenib is the global standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC), it does not have reliable predictive or prognostic biomarkers. Circulating cell-free DNA (cfDNA) has shown promise as a biomarker for various cancers. We investigated the use of cfDNA to predict clinical outcomes in HCC patients treated with sorafenib. METHODS: This prospective biomarker study analyzed plasma cfDNA from 151 HCC patients who received first-line sorafenib and 14 healthy controls. The concentration and VEGFA-to-EIF2C1 ratios (the VEGFA ratio) of cfDNA were measured. Low depth whole-genome sequencing of cfDNA was used to identify genome-wide copy number alteration (CNA), and the I-score was developed to express genomic instability. The I-score was defined as the sum of absolute Z-scores of sequenced reads on each chromosome. The primary aim of this study was to develop cfDNA biomarkers predicting treatment outcomes of sorafenib, and the primary study outcome was the association between biomarkers with treatment efficacy including disease control rate (DCR), time to progression (TTP) and overall survival (OS) in these patients. RESULTS: The cfDNA concentrations were significantly higher in HCC patients than in healthy controls (0.71 vs. 0.34 ng/µL; P < 0.0001). Patients who did not achieve disease control with sorafenib had significantly higher cfDNA levels (0.82 vs. 0.63 ng/µL; P = 0.006) and I-scores (3405 vs. 1024; P = 0.0017) than those achieving disease control. The cfDNA-high group had significantly worse TTP (2.2 vs. 4.1 months; HR = 1.71; P = 0.002) and OS (4.1 vs. 14.8 months; HR = 3.50; P < 0.0001) than the cfDNA-low group. The I-score-high group had poorer TTP (2.2 vs. 4.1 months; HR = 2.09; P < 0.0001) and OS (4.6 vs. 14.8 months; HR = 3.35; P < 0.0001). In the multivariable analyses, the cfDNA remained an independent prognostic factor for OS (P < 0.0001), and the I-score for both TTP (P = 0.011) and OS (P = 0.010). The VEGFA ratio was not significantly associated with treatment outcomes. CONCLUSION: Pretreatment cfDNA concentration and genome-wide CNA in cfDNA are potential biomarkers predicting outcomes in advanced HCC patients receiving first-line sorafenib.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Variações do Número de Cópias de DNA , Amplificação de Genes , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ácidos Nucleicos Livres/sangue , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Sorafenibe/farmacologia , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/sangue
19.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(4): 268-274, 2019 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-30955284

RESUMO

Objective: CD(4)(+)T cells, cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and vascular endothelial growth factor (VEGF) are associated with cancer development. The aim of the present study was to investigate the expression of CTLA-4, PD-1 and VEGF in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: From January 2017 to January 2018, a total of 47 first-visit outpatients were recruited in the Sleep and Respiratory Disorder Center of Guangdong Provincial People's Hospital, and were divided into control group (N=17, mean age 54±12 years), mild-to-moderate OSAHS group (N=15, mean age 54±12 years) and severe OSAHS group (N=15, mean age 56±13 years). Venous blood was collected, plasma and cells were isolated, the expressions of PD-1 and CTLA-4 on the surface of CD(4)(+)T cells were detected by flow cytometry, and plasma VEGF was measured by enzyme linked immunosorbent assay. Results: The proportion of CD(4)(+)T cells in control group, mild-to-moderate OSAHS group and severe OSAHS group were respectively(38±8)%, (35±8)% and (38±6)% (F=1.228, P>0.05). The expression of CTLA-4 on CD(4)(+)T cells were respectively [1.13 (0.59~1.78)]%, [0.45 (0.16~1.43)]% and [0.87(0.47~1.46)]% (H=2.205, P>0.05). The expression of PD-1 on CD(4)(+)T cells were respectively [4.24 (2.12~6.03)]%, [3.54(2.69~5.09)]% and [3.31(1.67~8.25)]% (H=0.541, P>0.05). The concentrations of VEGF in control group, mild-to-moderate OSAHS group and severe OSAHS group were statistically different [(395.16±87.78) ng/L vs (452.85±107.97) ng/L vs (546.42±199.27) ng/L, F=4.827, P=0.013]. Compared with the control group, VEGF concentration was significantly increased in the severe OSAHS group(P<0.01). VEGF concentration was correlated negatively with the lowest SpO(2) (r (s)=-0.480,P=0.001), but positively with apnea-hypopnea index(r (s)=0.403, P=0.005), oxygen desaturation index (r (s)=0.378, P=0.010) and proportion of SpO(2) less than or equal to 90% of total sleep time(r (s)=0.547, P=0.000 3). Conclusion: There was no significant difference of PD-1 and CTLA-4 expression on CD(4)(+)T cells in patients with and without OSAHS. The expression of VEGF was elevated in OSAHS patients, and increased with the severity of OSAHS and hypoxia.


Assuntos
Antígeno CTLA-4/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Apneia Obstrutiva do Sono/sangue , Linfócitos T/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Antígeno CTLA-4/sangue , Estudos de Casos e Controles , Humanos , Pessoa de Meia-Idade , Polissonografia , Receptor de Morte Celular Programada 1/sangue , Apneia Obstrutiva do Sono/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/sangue
20.
Angiology ; 70(9): 797-801, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30969784

RESUMO

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. The criteria required for the diagnosis identify various phenotypes, with different reproductive, metabolic, and cardiovascular (CV) risk characteristics. Emerging evidence links adipocyte-secreted hormones as candidates in the pathogenesis of endothelial dysfunction in PCOS, independently of additional risk factors. The aim of this review was to collect, analyze, and qualitatively resynthesize evidence on biomarkers of endothelial dysfunction (visfatin, vascular endothelial growth factor [VEGF], matrix metalloproteinase 9 [MMP-9]) in women with PCOS. Women with PCOS exhibit (a) increased plasma visfatin concentrations compared with controls with a similar body mass index; (b) increased VEGF production along with chronic, mild inflammation; and (c) increased MMP-9 concentrations, which might be related to either excessive CV risk or abnormalities of ovarian extracellular matrix remodeling, multiple cyst formation, follicular atresia, and chronic anovulation. As PCOS has been associated with CV risk, early identification of endothelial dysfunction is clinically relevant.


Assuntos
Biomarcadores/sangue , Endotélio Vascular/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Síndrome do Ovário Policístico/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/terapia , Doenças Vasculares/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/sangue
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