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1.
PLoS One ; 15(10): e0239370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33017430

RESUMO

BACKGROUND: Serum vascular endothelial growth factor (VEGF) and infarct volume detected by brain imaging have been associated with stroke outcome. However, the relationship of these two variables with post-stroke cognitive impairment (PSCI) remains unclear. We aimed to investigate the association between acute serum VEGF levels and infarct volume with PSCI in ischemic stroke patients. METHODS: Fifty-six first-ever ischemic stroke patients who were hospitalized in Dr. Sardjito General Hospital Yogyakarta, Indonesia were prospectively recruited. Serum VEGF level was taken on day 5 of stroke onset and measured by ELISA. Infarct volume was calculated manually from head CT scan by expert radiologist. PSCI was assessed after 3 months follow up by using Montreal Cognitive Assessment-Indonesian version (MoCA-INA). We performed a ROC curve analysis to determine the cut-off point of VEGF level and infarct volume. Multivariate logistic regression analysis was performed to measure the contribution of VEGF level and infarct volume to PSCI after controlling covariates (demographic and clinical data). RESULTS: The mean age of PSCI and non-PSCI patients was 61.63% ± 8.47 years and 58.67% ± 9.01 years, respectively (p = 0.221). No differences observed for vascular risk factors, infarct location, and NIHSS in both groups. Multivariate logistic regression showed that patients with higher VEGF level alone (≥519.8 pg/ml) were 4.99 times more likely to have PSCI than those with lower VEGF level (OR = 4.99, 95% CI = 1.01-24.7, p = 0.048). In addition, patients with larger infarct volume alone (≥0.054 ml) were also more frequently associated with PSCI (OR = 7.71, 95% CI = 1.39-42.91, p = 0.019). CONCLUSIONS: Acute ischemic stroke patients with higher serum VEGF level (≥519.8 pg/ml) and larger infarct volume (≥0.054 ml) were more likely to have PSCI 3 months after stroke. These findings may contribute to predict PSCI earlier and thus better prevention strategy could be made.


Assuntos
Infarto Encefálico/sangue , Infarto Encefálico/complicações , Disfunção Cognitiva/complicações , Fator A de Crescimento do Endotélio Vascular/sangue , Infarto Encefálico/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
Am J Clin Oncol ; 43(9): 621-627, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889831

RESUMO

OBJECTIVES: Despite the initial clinical benefit, resistance to antiangiogenic therapies develops through the activation of alternative pathways. We measured plasma levels of circulating angiogenic factors to explore their predictive role in metastatic renal cell carcinoma (mRCC) patients treated with pazopanib. MATERIALS AND METHODS: mRCC patients receiving first-line pazopanib were prospectively enrolled. The levels of circulating interleuchine (IL)-6, IL-8, stromal derived factor-1, vascular endothelial growth factor-A, hepatocyte growth factor (HGF), osteopontin, and E-selectin were quantified at baseline and every 4 weeks until disease progression (PD). Patients were dichotomized into "low" and "high" subgroups by a cutoff point defined by the respective median circulating angiogenic factor (CAF) value at baseline. Then, association with the objective response was determined. Changes in CAF levels between baseline and PD were also compared. RESULTS: Among 25 patients included in the final data set, 6 patients were still on treatment. As best response, 12 patients presented a partial response (48%), 9 showed stable disease, and 4 showed PD. The median follow-up was 31.9 months. The median progression-free survival was 14.8 months. Low baseline levels of IL-6, IL-8, HGF, and osteopontin were found to be significantly associated with objective response. In addition, patients with low baseline levels of HGF showed longer progression-free survival and overall survival, whereas patients with low baseline levels of IL-8 showed longer overall survival. Among patients experiencing PD, the median plasma levels of stromal derived factor-1 and vascular endothelial growth factor-A were significantly higher compared with the baseline (P=0.01; P=0.011). Conversely, the median levels of E-selectin were significantly lower compared with the baseline (P=0.017). CONCLUSION: Changes in levels of selected CAFs were associated with response/resistance to pazopanib in mRCC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/secundário , Quimiocina CXCL12/sangue , Progressão da Doença , Selectina E/sangue , Feminino , Fator de Crescimento de Hepatócito/sangue , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Neoplasias Renais/sangue , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Osteopontina/sangue , Intervalo Livre de Progressão , Estudos Prospectivos , Critérios de Avaliação de Resposta em Tumores Sólidos , Taxa de Sobrevida , Pesquisa Médica Translacional , Fator A de Crescimento do Endotélio Vascular/sangue
3.
Medicine (Baltimore) ; 99(33): e21565, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872007

RESUMO

BACKGROUND: In recent years, more and more attention has been paid to the role of skin microcirculation in the pathogenesis of psoriasis. The vascular network of the skin is mainly distributed in the dermis and the subcutaneous fat layer join. The microvessels are composed of terminal arterioles, arteriovenous capillaries, and postcapillary venules. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of psoriasis by promoting angiogenesis. The purpose of this study is to evaluate the relationship between serum VEGF and psoriasis vulgaris. METHODS: Embase, CENTRAL, PubMed, China Biology Medicine Database, China National Knowledge Database, Wan Fang Database, and Chong Qing VIP Database will be searched to collect case-control studies and cohort studies and evaluate the relationship between serum VEGF and psoriasis vulgaris. The search time limits will be from the establishment of the database to December 2020. Two researchers will independently screen the studies, extract data, and evaluate the risk of bias of the studies. The Meta-analysis will be carried out with the RevMan5.3 software. The quality of all included studies will be evaluated by the Newcastle-Ottawa scale. RESULTS: This study will evaluate the relationship between serum VEGF and the pathogenesis of psoriasis vulgaris. CONCLUSION: This study will provide a theoretical basis for the pathogenesis of psoriasis vulgaris. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/6DV8P.


Assuntos
Psoríase/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Estudos de Casos e Controles , Humanos , Projetos de Pesquisa
4.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32669404

RESUMO

Hereditary hemorrhagic telangiectasia (HHT) can be clinically diagnosed, but children often lack characteristic features. We report a family with homozygous growth differentiation factor 2 (GDF2)-related HHT diagnosed by genetic testing. A boy aged 5 years and 2 months presented with isolated hypoxemia. He was the product of a consanguineous marriage; his parents were second cousins. Physical examination revealed cyanosis of nail beds and clubbed fingers. Pulse oxygen saturation was 84% to 89%. Lung function, contrast-enhanced lung computed tomography, and noncontrast echocardiography were normal. A pulmonary perfusion scan revealed radioactivity in the brain and bilateral kidney, suggesting the existence of a intrapulmonary shunt. Whole-exome sequencing revealed a homozygous variant [c.1060_1062delinsAG (p.Tyr354ArgfsTer15)] in GDF2, which was found to be inherited from his heterozygous parents. At the age of 8 years, he developed epistaxis, and an angiogram revealed diffuse pulmonary arteriovenous malformations. At the age of 9 years, he was treated with sirolimus, and his condition improved significantly. However, his now 7-year-old sister with the same homozygous variant currently has no symptoms. Physical examinations revealed 1 pinpoint-sized telangiectasia on the chest of his mother and a vascular lesion on the forehead of his sister. Additionally, the patient's father and great-uncle had a history of mild to moderate epistaxis. Mutation in GDF2 is a rare cause of HHT. Ours is the first report of homozygous GDF2-related HHT; in addition, this variant has not been reported previously. In our report, we also confirm variable expressivity, even with the same pathogenic variant in GDF2-related HHT.


Assuntos
Fator 2 de Diferenciação de Crescimento/genética , Hipóxia/etiologia , Telangiectasia Hemorrágica Hereditária/genética , Grupo com Ancestrais do Continente Asiático/genética , Criança , Pré-Escolar , Consanguinidade , Endoglina/metabolismo , Epistaxe/etiologia , Feminino , Homozigoto , Humanos , Mutação INDEL , Mutação com Perda de Função , Masculino , Linhagem , Transdução de Sinais , Telangiectasia Hemorrágica Hereditária/sangue , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/diagnóstico por imagem , Fator de Crescimento Transformador beta/fisiologia , Fator A de Crescimento do Endotélio Vascular/sangue , Sequenciamento Completo do Exoma
5.
PLoS One ; 15(7): e0235859, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687494

RESUMO

In our work, we aim to identify new candidate host biomarkers to discriminate between active TB patients (n = 28), latent infection (LTBI; n = 27) and uninfected (NoTBI; n = 42) individuals. For that, active TB patients and their contacts were recruited that donated serum and saliva samples. A multiplex assay was performed to study the concentration of different cytokines, chemokines and growth factors. Proteins with significant differences between groups were selected and logistic regression and the area under the ROC curve (AUC) was used to assess the diagnostic accuracy. The best marker combinations that discriminate active TB from NoTBI contacts were [IP-10 + IL-7] in serum and [Fractalkine + IP-10 + IL-1α + VEGF] in saliva. Best discrimination between active TB and LTBI was achieved using [IP-10 + BCA-1] in serum (AUC = 0.83) and IP-10 in saliva (p = 0.0007; AUC = 0.78). The levels of TNFα (p = 0.003; AUC = 0.73) in serum and the combination of [Fractalkine+IL-12p40] (AUC = 0.83) in saliva, were able to differentiate between NoTBI and LTBI contacts. In conclusion, different individual and combined protein markers could help to discriminate between active TB and both uninfected and latently-infected contacts. The most promising ones include [IP-10 + IL-7], [IP-10 + BCA-1] and TNFα in serum and [Fractalkine + IP-10 + IL-1α + VEGF], IP-10 and [Fractalkine+IL-12p40] in saliva.


Assuntos
Quimiocina CX3CL1/sangue , Quimiocina CXCL10/sangue , Interleucinas/sangue , Tuberculose Latente/sangue , Tuberculose Pulmonar/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Quimiocina CX3CL1/análise , Quimiocina CXCL10/análise , Feminino , Humanos , Interleucinas/análise , Tuberculose Latente/diagnóstico , Tuberculose Latente/metabolismo , Masculino , Pessoa de Meia-Idade , Saliva/química , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/metabolismo , Fator A de Crescimento do Endotélio Vascular/análise
6.
J Infect Dis ; 222(5): 746-754, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32563194

RESUMO

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the serum cytokine and chemokine levels in asymptomatic, mild, moderate, severe, and convalescent SARS-CoV-2-infected cases. Proinflammatory cytokine and chemokine production induced by SARS-CoV-2 were observed not only in symptomatic patients but also in asymptomatic cases, and returned to normal after recovery. IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, MCP-1, MCP-3, IP-10, MIG, and MIP-1α were found to be associated with the severity of COVID-19. Moreover, a set of cytokine and chemokine profiles were significantly higher in SARS-CoV-2-infected male than female patients. The serum levels of MCP-1, G-CSF, and VEGF were weakly and positively correlated with viral titers. We suggest that combinatorial analysis of serum cytokines and chemokines with clinical classification may contribute to evaluation of the severity of COVID-19 and optimize the therapeutic strategies.


Assuntos
Quimiocinas/sangue , Infecções por Coronavirus/sangue , Citocinas/sangue , Pneumonia Viral/sangue , Adulto , Betacoronavirus/isolamento & purificação , Quimiocina CCL2/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular/sangue , Carga Viral
7.
J Cancer Res Ther ; 16(2): 335-342, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474521

RESUMO

Context: Osteosarcoma (OS) is a progressive primary bone tumor that originates from immature stromal spindle cells. After chemotherapy, the serum-related indexes which are related to the prognosis. Aims: The aim of this study is to investigate the correlation between changes in serum cyclooxygenase-2 (COX-2), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-ß), and tumor-specific growth factor (TSGF) levels and prognosis of patients with osteosarcoma (OS) before and after treatment. Settings and Design: Data of 75 patients with OS (observation group) and 55 healthy controls (control group) were retrospectively analyzed. Materials and Methods: Chemotherapy was administered to the observation group. Serum lactate dehydrogenase, alkaline phosphatase, and TSGF levels were measured before and after treatment. The observation group patients were classified as normal or abnormal according to the changes in serum COX-2, bFGF, VEGF, TGF-ß, and TSGF levels after chemotherapy. Patients were followed up for 7.5 years, and the survival rate was determined. Statistical Analysis Used: Single-factor influencing prognosis was included in the Cox model, and independent factors influencing prognosis were analyzed. Results: After chemotherapy, the mean serum COX-2, bFGF, VEGF, and TSGF levels decreased significantly in the observation group but were still higher than those in the control group. Furthermore, serum TGF-ß levels increased in the observation group but were still lower than those in the control group. The 5-year survival rate of patients with normal serum COX-2, bFGF, VEGF, and TSGF levels was significantly higher in the normal subgroup than in the abnormal subgroup. Cox analysis showed that the Enneking stage and COX-2 level after chemotherapy were independent prognostic factors. Conclusions: The serum COX-2, bFGF, VEGF, and TSGF levels of patients with OS significantly changed after chemotherapy, and the short-term survival rate of patients with normal levels of these biomarkers after chemotherapy was high.


Assuntos
Biomarcadores Tumorais/sangue , Osteossarcoma/sangue , Osteossarcoma/patologia , Adolescente , Adulto , Antígenos de Neoplasias/sangue , Neoplasias Ósseas/sangue , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Estudos de Casos e Controles , Criança , Ciclo-Oxigenase 2/sangue , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/sangue , Feminino , Fator 2 de Crescimento de Fibroblastos/sangue , Humanos , Masculino , Proteínas de Neoplasias/sangue , Osteossarcoma/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fator de Crescimento Transformador beta/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
8.
Medicine (Baltimore) ; 99(24): e20562, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541481

RESUMO

BACKGROUND: Diabetic retinopathy (DR) remains the most common microvascular complication of diabetes; both its high prevalence and associated high risk of vision loss lead it to the major global health burden. Despite significant research efforts, there still remains much of the underlying pathology not fully understand. In the past studies, inner retinal blood flow disturbances are widely assessed as a potential biomarker of DR. However, the results have been variable and even contradictory. Improved methods to figure out the metabolic disturbances associated with DR are essential. Some research showed that both vascular endothelial growth factor-A and blood oxygen saturation are higher in DR patients and correlated with disease severity. Therefore, we decided to conduct a systematic review and meta-analysis to find out the connection of them and provide robust evidence on the mechanism underlying this connection to help us better understand the pathophysiology behind the hypoxic retina and find better ways to treat DR. METHODS: This study will be conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will do electronic searches from PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database, CNKI, and VIP database. Two reviewers will screen all the references independently and any disagreement will be solved by the third involvement. All data will be extracted by 2 independent reviewers according to a standardized data extraction sheet. Based on the type of studies, 2 reviewers will independently use different scales to assess the risk of bias. Any disagreements and conflicts will be resolved by discussing it with a third reviewer. We will conduct a random-effects meta-analysis. Individual and pooled odds ratios/relative risks and associated 95% confidence intervals will be calculated as well as between-study heterogeneity. The potential for publication bias will also be evaluated. If possible, we will explore reasons for potential between-study heterogeneity. RESULTS: This study is a protocol for systematic review and meta-analysis without results. Associated data analysis will be carried out after the protocol. CONCLUSION: The protocol aims to guide a meta-analysis whose purpose is investigating the association between retinal blood oxygen saturation and vascular endothelial growth factors in patients with early DR and trying to find out the mechanism that the changing of retinal oxygen saturation in patients with DR. INPLASY REGISTRATION NUMBER: INPLASY202040161.


Assuntos
Retinopatia Diabética/sangue , Oxigênio/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
9.
Neurology ; 94(23): e2412-e2423, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32461282

RESUMO

OBJECTIVE: To measure exosomal and plasma levels of candidate blood biomarkers in veterans with history of mild traumatic brain injury (mTBI) and test their relationship with chronic symptoms. METHODS: Exosomal and plasma levels of neurofilament light (NfL) chain, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and vascular endothelial growth factor (VEGF) were measured using an ultrasensitive assay in a cohort of 195 veterans, enrolled in the Chronic Effects of Neurotrauma Consortium Longitudinal Study. We examined relationships between candidate biomarkers and symptoms of postconcussive syndrome (PCS), posttraumatic stress disorder (PTSD), and depression. Biomarker levels were compared among those with no traumatic brain injury (TBI) (controls), 1-2 mTBIs, and repetitive (3 or more) mTBIs. RESULTS: Elevated exosomal and plasma levels of NfL were associated with repetitive mTBIs and with chronic PCS, PTSD, and depression symptoms. Plasma TNF-α levels correlated with PCS and PTSD symptoms. The total number of mTBIs correlated with exosomal and plasma NfL levels and plasma IL-6. Increased number of years since the most recent TBI correlated with higher exosomal NfL and lower plasma IL-6 levels, while increased number of years since first TBI correlated with higher levels of exosomal and plasma NfL, as well as plasma TNF-α and VEGF. CONCLUSION: Repetitive mTBIs are associated with elevated exosomal and plasma levels of NfL, even years following these injuries, with the greatest elevations in those with chronic PCS, PTSD, and depression symptoms. Our results suggest a possible neuroinflammatory and axonal disruptive basis for symptoms that persist years after mTBI, especially repetitive.


Assuntos
Concussão Encefálica/sangue , Exossomos/química , Proteínas de Neurofilamentos/sangue , Saúde dos Veteranos , Veteranos , Adulto , Biomarcadores , Traumatismos por Explosões/sangue , Traumatismos por Explosões/complicações , Concussão Encefálica/complicações , Estudos Transversais , Depressão/sangue , Depressão/etiologia , Feminino , Seguimentos , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Síndrome Pós-Concussão/sangue , Síndrome Pós-Concussão/etiologia , Prognóstico , Degeneração Retrógrada , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/sangue , Transtornos de Estresse Pós-Traumáticos/etiologia , Fator de Necrose Tumoral alfa/análise , Fator A de Crescimento do Endotélio Vascular/sangue , Guerra
10.
J Cancer Res Clin Oncol ; 146(7): 1725-1735, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32394054

RESUMO

OBJECTIVE: The plasminogen activator system (PAS) and vascular endothelial growth factor (VEGF) are important in the carcinogenesis and play a key role in cancer invasion and mediating metastasis of carcinomas. The aim of the study was to evaluate the correlation of serum levels of VEGF and components of the PAS with clinicopathological risk factors and outcome in patients with endometrial cancer (EC). METHODS: Preoperative blood was collected from 173 patients treated for EC between 1999 and 2009. Serum concentrations of VEGF, urokinase plasminogen activator (uPA) tissue plasminogen activator (tPA), plasminogen activator inhibitor type-1 (PAI-1) and -2 (PAI-2) were assessed by enzyme-linked immunosorbent assays (ELISA). RESULTS: Serum levels of VEGF and components of the PAS were significantly associated with stage of the disease, tumor histology, tumor grade, myometrial invasion (MI), presence of lymphovascular space invasion (LVSI) and lymph node metastases (LNM). Preoperative serum levels of PAI-1 and -2 and tPA were higher in patients who experienced a recurrence than in patients who remained disease free (p < 0.01). PAI-1 and -2 and tPA were significantly independent prognostic factors for DFS with a HR of 3.85 (95% CI 1.84-8.07), 3.90 (95% CI 1.75-8.66) and 2.53 (95% CI 1.16-5.55), respectively. PAI-1 and tPA turned out to be independent prognostic factors for OS, with a HR of 2.09 (95% CI 1.08-4.05) and 2.16 (95% CI 1.06-4.44), respectively. CONCLUSION: Serum levels of VEGF and components of the PAS at primary diagnosis were associated with well-known clinicopathological risk factors such as; FIGO stage, tumor histology, tumor grade, MI, LVSI and LNM. High concentrations of PAI-1 and-2 and tPA are independent factors for poor prognosis in patients with endometrial cancer.


Assuntos
Neoplasias do Endométrio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Idoso , Biomarcadores Tumorais , Transformação Celular Neoplásica , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/mortalidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Modelos Moleculares , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Ativador de Plasminogênio Tecidual/sangue , Ativador de Plasminogênio Tecidual/metabolismo , Fator A de Crescimento do Endotélio Vascular/sangue
11.
J Sports Med Phys Fitness ; 60(5): 677-684, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32438783

RESUMO

BACKGROUND: Erythropoietin (EPO) and vascular endothelial growth factor (VEGF) are important factors regulating erythropoiesis and angiogenesis. Altitude/hypoxic training may induce elevated VEGF-A and EPO levels. However, it appears that the range of adaptive changes depends largely on the training method used. Therefore, we investigated the changes in EPO and VEGF-A levels in athletes using three different altitude/hypoxic training concepts. METHODS: Thirty-four male cyclists were randomly divided into four groups: LH-TL group ("live high-train low" protocol), HiHiLo ("live high - base train high - interval train low" procedure), IHT ("intermittent hypoxic training") and control group (CN, normoxic training). The same 4-week training program was used in all groups. Blood samples were taken before and after each training week in order to evaluate serum EPO and VEGF-A levels. RESULTS: In the LH-TL and HiHiLo groups, EPO increased (P<0.001) after 1st week and remained elevated until 3rd week of altitude training. In the IHT and CN groups, EPO did not change significantly. VEGF-A was higher (P<0.001) after 2nd and 3rd week of training in the IHT group. In the HiHiLo group, VEGF-A changed (P<0.05) only after 3rd week. No significant changes of VEGF-A were noted in the LH-TL and CN groups. CONCLUSIONS: Altitude/hypoxic training is effective in increasing VEGF-A and EPO levels. However, a training method plays a key role in the pattern of adaptations. EPO level increase only when an adequate hypoxic dose is provided, whereas VEGF-A increases when the hypoxic exposure is combined with exercise, particularly at high intensity.


Assuntos
Aclimatação/fisiologia , Eritropoetina/sangue , Exercício Físico/fisiologia , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Altitude , Humanos , Hipóxia/sangue , Masculino , Adulto Jovem
12.
Adv Clin Exp Med ; 29(4): 493-497, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32338833

RESUMO

BACKGROUND: Patients with coronary chronic total occlusion (CTO) typically have collateralization of the distal vessel, and these collaterals can contribute to the relief of ischemia and anginal symptoms and to the preservation of ventricular function. OBJECTIVES: To investigate the preservation effect of coronary collateral circulation on left ventricular (LV) function in coronary CTO, and to explore the potential mechanism behind the development of coronary collateral circulation. MATERIAL AND METHODS: A total of 102 consecutive patients with coronary CTO were divided into 2 groups: the left ventricular ejection fraction (LVEF)-preserved group (LVEF ≥ 50%; n = 46) and the LVEF-decreased group (LVEF < 50%; n = 56). Clinical, angiographic and laboratory data was collected for all patients. The association between LVEF and coronary collateral circulation in coronary CTO patients was analyzed with multivariate logistic regression analysis, and the serum levels of VEGF-A and the mRNA expression levels of the VEGF-A gene were compared between different grades of coronary collateral circulation. RESULTS: Multivariate analysis revealed that Rentrop grades 2-3 and coexisting collateral pathways were independent predictors of LVEF preservation in coronary CTO patients. Patients with Rentrop grades 2-3 had smaller left ventricular end diastolic diameters (LVDd) and left ventricular end systolic diameters (LVSd), and they had larger LVEFs than the patients with Rentrop grades 0-1. Patients with Rentrop grades 2-3 also had higher serum levels of VEGF-A and higher mRNA expression levels of the VEGF-A gene in their peripheral blood mononuclear cells (PBMCs) than patients with Rentrop grades 0-1. Patients with coexisting collateral pathways had higher serum levels of VEGF-A and higher mRNA expression levels of the VEGF-A gene in PBMCs than patients without coexisting collateral pathways. CONCLUSIONS: Coronary collateral circulation is significantly associated with LVEF preservation, and VEGF-A might promote the formation of coronary collateral circulation.


Assuntos
Circulação Colateral , Circulação Coronária , Oclusão Coronária , Leucócitos Mononucleares , Fator A de Crescimento do Endotélio Vascular/sangue , Função Ventricular Esquerda/fisiologia , Angiografia Coronária , Humanos , Intervenção Coronária Percutânea , Volume Sistólico , Fator A de Crescimento do Endotélio Vascular/genética
13.
Cancer Chemother Pharmacol ; 85(5): 941-947, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32279102

RESUMO

PURPOSE: The aim of this study was to investigate the association between changes in the levels of vascular endothelial growth factors (VEGFs) after treatment with bevacizumab and gemcitabine (Bev-Gem) and the clinical outcome. METHODS: Platinum-resistant ovarian cancer patients treated with Bev-Gem therapy at our hospital between 2014 and 2018 were identified. Serum VEGF levels at the first and second treatment cycle were measured by ELISA. All patients were categorized into two groups-patients with > 50% decrease in serum VEGF-A levels (Group A) and patients with < 50% decrease serum VEGF-A levels (Group B). The association between clinical outcome and serum VEGF levels was investigated between the two groups. RESULTS: Among 18 patients, 10 were in Group A and 8 in Group B. Group A exhibited a lower response rate (0% vs.75% p < 0.01) and clinical benefit rate (60% vs.100% p = 0.02) than Group B. The median serum VEGF-A level of Group A before the first cycle of Bev-Gem therapy was higher than that in Group B (61.2 vs. 3.7 pg/mL, p < 0.01). Group A exhibited worse PFS (7 vs., 10 months, p < 0.01) and OS (17 vs. 26 months, p = 0.04) than Group B. There were more patients with > 10% increase in serum VEGF-B levels in Group A than in Group B (p < 0.01). CONCLUSION: The rapid decrease in VEGF-A levels and the resultant increase in serum VEGF-B levels might be associated with an unfavorable clinical outcome. Large-scale studies are needed to further examine these results.


Assuntos
Bevacizumab , Cisplatino/farmacologia , Desoxicitidina/análogos & derivados , Recidiva Local de Neoplasia , Neoplasias Ovarianas , Fator A de Crescimento do Endotélio Vascular/sangue , Fator B de Crescimento do Endotélio Vascular/sangue , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Bevacizumab/farmacocinética , Biomarcadores Farmacológicos/sangue , Biomarcadores Tumorais/sangue , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/farmacocinética , Progressão da Doença , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Valor Preditivo dos Testes , Prognóstico
14.
Semin Ophthalmol ; 35(2): 126-133, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32310727

RESUMO

Purpose: To investigate the aqueous humor and serum levels of selected cytokines and vascular endothelial growth factor (VEGF) in diabetic patients, implicating their role in the pathogenesis of diabetic eye complications.Materials and methods:   Atotal of 65 patients (27 males and 38 females) who underwent cataract surgery were recruited into the study. The study group consisted of 30 cataract patients with type 2 diabetes mellitus, and this group was divided into two subgroups: 14 patients with diabetic retinopathy (DR group) and 16 patients without DR (NDR group). The control group consisted of 35 non-diabetic cataract subjects.Results: Patients in the DR group had significantly higher aqueous humor concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, monocyte chemotactic protein (MCP-1) and VEGF. Likewise, serum concentrations of IL-1ß, IL-6, IL-8, IL-12, TNF-α and IFN-γ were significantly higher in the DR group as compared to the controls. Aqueous humor concentrations of IL-1ß, IL-8, MCP-1 and VEGF were significantly higher in the DR group as compared with the NDR group.Conclusion: Our findings support the hypothesis that chronic inflammation and a disturbance of the immune system play important roles in the pathogenesis of diabetic cataract and DR.


Assuntos
Humor Aquoso/metabolismo , Citocinas/sangue , Retinopatia Diabética/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Idoso , Diabetes Mellitus Tipo 2/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade
15.
Cancer Immunol Immunother ; 69(7): 1229-1236, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32152703

RESUMO

The efficacy of immune checkpoint inhibitors (ICIs) in elderly and poor performance status (PS) patients is controversial, because clinical evidence is limited. This study aimed to find a predictive biomarker for the efficacy of anti-programmed cell death 1 (PD-1) antibodies in these patient populations. We retrospectively reviewed medical records of advanced non-small-cell lung cancer (NSCLC) patients who were ≥ 75 years of age or classified as PS 2 and received anti-PD-1 antibody treatment between December 2015 and May 2018. We evaluated the association between the efficacy of the anti-PD-1 antibody in these patients and the clinical variables thought to affect ICI efficacy. A total of 235 patients with advanced NSCLC were treated with anti-PD-1 antibodies, among whom 31 patients were ≥ 75 years of age and 22 were PS 2. A Cox proportional hazard model showed that only high levels of serum vascular endothelial growth factor (VEGF) were significantly associated with a shorter progression-free survival in patients aged ≥ 75 years and those with PS 2. Among these cohorts, the overall response rate to anti-PD-1 treatment tended to be lower when serum VEGF was high compared to patients with low serum VEGF. Our results demonstrate that serum VEGF concentration may be a negative predictive biomarker in elderly and poor PS advanced NSCLC patients receiving anti-PD-1 antibody treatment. This finding may help identify patients who will not benefit from anti-PD-1 antibody therapy.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
16.
Medicine (Baltimore) ; 99(11): e19292, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176054

RESUMO

BACKGROUND: The aim of the study was to provide a theoretical basis for the early diagnosis and prediction of acute altitude sickness, to provide a better entry mode for healthy people from plain areas to plateau areas, and to preliminarily clarify the possible mechanism of this approach. METHODS: We measured endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), nitric oxide (NO), and hypoxia-inducible factor 1 (HIF-1) levels in each sample and determined flow-mediated dilation (FMD) values using a portable OMRON color Doppler with a 7.0- to 12.0-MHz linear array probe. We used the Lewis Lake score to diagnose acute mountain sickness (AMS) and to stratify the disease severity. RESULTS: We found no cases of AMS at any of the studied elevation gradients. We found significant differences in FMD values between individuals when at 400 m above sea level and when at 2200, 3200, and 4200 m above sea level (P < .05) but found no significant differences among those at 2200, 3200, and 4200 m. Our variance analysis showed that serum ET-1, VEGF, ADMA, NO, and HIF-1 levels in individuals at ≥3000 m and those at subplateau and plain areas (<3000 m) significantly differed (P < .05). The level of these factors also significantly differed between individuals at elevation gradients of plateau areas (3260 m vs 4270 m) (P < .05). We found no significant differences in serum ET-1, VEGF, and ADMA levels between individuals at the plateau (2260 m) and plain (400 m) areas (P > .05). NO and HIF-1 levels were significantly different in serum samples from individuals between the plateau (2260 m) and plain (400 m) areas (P < .05). However, with increasing altitude, the NO level gradually increased, whereas ET-1, ADMA, VEGF, and HIF-1 levels showed a decreasing trend. With the increase of altitude, there is no correlation between the trend of FMD and hematologic-related factors such as VEGF, NO, and HIF-1. CONCLUSION: A healthy young male population ascending to a high-altitude area experiences a low incidence of AMS. Entering an acute plateau exposure environment from different altitude gradients may weaken the effect of acute highland exposure on vascular endothelial dysfunction in healthy individuals. Changes in serum ET-1, VEGF, ADMA, NO, and HIF-1 levels in healthy young men may be related to the body's self-regulation and protect healthy individuals from AMS. A short stay in a subplateau region may initiate an oxygen-free preconditioning process in healthy individuals, thereby protecting them from AMS. Noninvasive brachial artery endothelial function test instead of the detection of invasive hematologic-related factors for early diagnosis and prediction of the occurrence and severity of acute high-altitude disease is still lack of sufficient theoretical basis.


Assuntos
Doença da Altitude/sangue , Altitude , Endotelina-1/sangue , Fator 1 Induzível por Hipóxia/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Doença Aguda , Adulto , Doença da Altitude/diagnóstico , Análise de Variância , Biomarcadores/sangue , China , Diagnóstico Precoce , Voluntários Saudáveis , Humanos , Masculino , Militares , Óxido Nítrico/sangue , Valores de Referência , Sensibilidade e Especificidade , Adulto Jovem
17.
BMC Cancer ; 20(1): 159, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32106836

RESUMO

BACKGROUND: Lung cancer is the major malignant tumour. The present study was conducted to determine the expression level of syntenin in lung cancer tissues and serum from lung cancer patients and to explore its clinical significance. METHODS: Syntenin expression levels were determined in paraffin-embedded lung cancer tissue specimens (n = 191) using immunohistochemistry. The mRNA expressions of syntenin in fresh lung cancer tissues and the paracancerous tissues were examined by RT-qPCR (n = 25). Syntenin and VEGF expression levels were measured in serum from patients with lung cancer (n = 60) and control subjects (n = 30) using ELISA. The associations between syntenin and the clinicopathological features or prognosis in 191 patients with lung cancer were analysed. The correlation between the syntenin and VEGF levels in serum from 60 lung cancer patients was analysed. RESULTS: The expression levels of syntenin were significantly higher in lung cancer tissues than in paracancerous tissues based on immunohistochemistry and RT-qPCR, and elevated syntenin expression was significantly associated with tumour size (P = 0.002), TNM stage (P = 0.020), tumour distant metastasis (P = 0.033), overall survival (OS) (P = 0.002) and progression-free survival (PFS) (P = 0.001). Multivariate analysis revealed that increased expression of syntenin was an independent risk factor for OS (P = 0.006) and PFS (P < 0.001) in lung cancer patients. The expression levels of syntenin and VEGF in serum from lung cancer patients were higher than those from control subjects (P < 0.001, P < 0.001, respectively), and their expression levels were positively correlated (r = 0.49, P < 0.001). CONCLUSIONS: Syntenin expression is upregulated in lung cancer patients, and its serum expression level is positively correlated with VEGF. Moreover, syntenin overexpression was correlated with poor prognosis in patients with lung cancer.


Assuntos
Neoplasias Pulmonares/patologia , Sinteninas/genética , Sinteninas/metabolismo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Sinteninas/sangue , Adulto Jovem
18.
Intern Med ; 59(9): 1149-1153, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32009091

RESUMO

Objective A randomized controlled trial has shown the efficacy of thalidomide against polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome; however, there are still refractory patients. We studied the effects of lenalidomide, a derivative of thalidomide, on patients refractory to thalidomide. Methods This prospective single-arm trial evaluated the safety and efficacy of lenalidomide plus dexamethasone in refractory or recurrent patients with POEMS syndrome. The regimen was administered as six 28-day cycles with lenalidomide on days 1-21 (15 mg in cycle 1, and 25 mg in cycle 2-6) plus dexamethasone once a week (20 mg). The primary endpoints were the rate of reduction in the serum vascular endothelial growth factor (VEGF) level at 24 weeks and the incidence of adverse events. This trial was registered with ClinicalTrial.gov, NCT02193698. Results Between July 2014 and December 2015, five men were enrolled. All patients had been refractory to thalidomide plus dexamethasone for more than 24 weeks. The mean rate of reduction in the serum VEGF level at 24 weeks was 59.6%±8.3% (p=0.0003). The mean serum VEGF level decreased from 2,466±771 pg/mL to 974±340 pg/mL. No serious adverse events were observed, and all patients completed six cycles treatment. Discussion Lenalidomide is a therapeutic option for thalidomide-refractory patients with POEMS syndrome.


Assuntos
Lenalidomida/uso terapêutico , Síndrome POEMS/tratamento farmacológico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Fatores Imunológicos , Lenalidomida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Síndrome POEMS/sangue , Estudos Prospectivos , Talidomida/administração & dosagem , Talidomida/uso terapêutico , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
19.
Microvasc Res ; 130: 103987, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32035919

RESUMO

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most devastating diabetic consequences leading to amputations. Oxidative stress, inflammation, vascular insufficiency and neuropathy have been linked to DFU development. Since soluble fms-like tyrosine kinase-1 (sFlt-1) is one of the anti-angiogenic factors regulating vascular endothelial growth factor (VEGF) biological activity. So, we aimed to evaluate its role in pathogenesis of DFU and its correlation with oxidative stress and inflammatory markers. METHODS: 60 type 2 diabetic patients: 30 without DFU and 30 with DFU in addition to 20 healthy controls were enrolled in the study. sFlt-1 and VEGF mRNA relative gene expressions and levels and sFlt-1/VEGF ratio were assessed. Also, Advanced oxidation protein products (AOPPs), malondialdhyde (MDA), Total thiol and, tumor necrosis factor alpha (TNF-α) levels were measured. RESULTS: sFlt-1 expression and level, AOPPs, MDA and TNF-α were significantly higher in diabetic patients as compared with the control group with highest levels in DFU patients. However, there were significant decrease in total thiol level and VEGF expression and level in diabetic patients with DFU. CONCLUSION: This study revealed that sFlt-1 is a major player in DFU pathogenesis and may be considered as a novel diagnostic biomarker for early detection of DFU.


Assuntos
Pé Diabético/sangue , Mediadores da Inflamação/sangue , Neovascularização Fisiológica , Estresse Oxidativo , Fator de Necrose Tumoral alfa/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Produtos da Oxidação Avançada de Proteínas/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Pé Diabético/enzimologia , Pé Diabético/patologia , Pé Diabético/fisiopatologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Compostos de Sulfidrila/sangue , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética
20.
Clin Immunol ; 213: 108364, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32087329

RESUMO

OBJECTIVES: To evaluate expansion of CD21low B cells and their role in B cell homeostasis, apoptosis, clinical manifestations and serum vascular endothelial growth factor (VEGF) in systemic sclerosis (SSc). MATERIALS AND METHODS: B-cells subpopulations and apoptosis have been assessed in 74 SSc patients and 20 healthy donors. Renal Doppler ultrasound, echocardiography, pulmonary function test and VEGF were performed. RESULTS: SSc patients with expanded CD21low B cells (SSc-CD21low) show a distinct B cell profile with increased memory B cells compared to patients without CD21low B cells (SSc-CD21+). Renal resistive index, systolic pulmonary arterial pressure and FVC/DLCO ratio were significantly higher in SSc-CD21low group than SSc-CD21+, DLCO was lower in SSc-CD21low group than SSc-CD21+. We found a positive linear correlation between CD21low and sPAP, RI and FVC/DLCO ratio whereas a negative correlation was observed between CD21low and DLCO and VEGF levels. CONCLUSIONS: CD21low B cells are increased in SSc patients with visceral vascular manifestations.


Assuntos
Subpopulações de Linfócitos B/imunologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/imunologia , Doenças Vasculares/etiologia , Idoso , Feminino , Cardiopatias/etiologia , Humanos , Nefropatias/etiologia , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Receptores de Complemento 3d/imunologia , Escleroderma Sistêmico/patologia , Fator A de Crescimento do Endotélio Vascular/sangue
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