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1.
Eur Radiol ; 30(1): 1-10, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31278580

RESUMO

OBJECTIVES: Various imaging methods have been evaluated regarding non-invasive differentiation of renal cell carcinoma (RCC) subtypes. Dual-energy computed tomography (DECT) allows iodine concentration (IC) analysis as a correlate of tissue perfusion. Microvascular density (MVD) in histopathology specimens is evaluated to determine intratumoral vascularization. The objective of this study was to assess the potential of IC and MVD regarding the differentiation between papillary and clear cell RCC and between well- and dedifferentiated tumors. Further, we aimed to investigate a possible correlation between these parameters. METHODS: DECT imaging series of 53 patients with clear cell RCC (ccRCC) and 15 with papillary RCC (pRCC) were analyzed regarding IC. Histology samples were stained using CD31/CD34 monoclonal antibodies; MVD was evaluated digitally. Statistical analysis included performance of Mann-Whitney U test, ROC analysis, and Spearman rank correlation. RESULTS: Analysis of IC demonstrated significant differences between ccRCC and pRCC (p < 0.001). A cutoff value of ≤ 3.1 mg/ml at IC analysis allowed identification of pRCC with an accuracy of 86.8%. Within the ccRCC subgroup, G1/G2 tumors could significantly be differentiated from G3/G4 carcinomas (p = 0.045). A significant positive correlation between IC and MVD could be determined for the entire RCC cohort and the ccRCC subgroup. Limitations include the small percentage of pRCCs. CONCLUSIONS: IC analysis is a useful method to differentiate pRCC from ccRCC. The significant positive correlation between IC and MVD indicates valid representation of tumor perfusion by DECT. KEY POINTS: • Analysis of iodine concentration using DECT imaging could reliably distinguish papillary from clear cell subtypes of renal cell cancer (RCC). • A cutoff value of 3.1 mg/ml allowed a distinction between papillary and clear cell RCCs with an accuracy of 86.8%. • The positive correlation with microvascular density in tumor specimens indicates correct display of perfusion by iodine concentration analysis.


Assuntos
Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/irrigação sanguínea , Carcinoma Papilar/diagnóstico por imagem , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/diagnóstico por imagem , Transformação Celular Neoplásica/patologia , Meios de Contraste/farmacocinética , Feminino , Humanos , Iodo/farmacocinética , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/diagnóstico por imagem , Masculino , Microvasos/diagnóstico por imagem , Microvasos/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Tomografia Computadorizada por Raios X/métodos , Carga Tumoral
2.
Invest Ophthalmol Vis Sci ; 60(14): 4520-4531, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675423

RESUMO

Purpose: To objectively quantify cone density (CD) and microvascular density (MVD) in normal subjects and patients with moderate or severe retinitis pigmentosa (RP) by adaptive optics (AO) and optical coherence tomography angiography (OCTA) and to evaluate the changes in the parafoveal regions. Method: Thirty-seven eyes from 20 RP patients and 54 eyes from 29 age-matched healthy participants underwent AO fundus and OCTA imaging. AO images covering a 3-mm-diameter area centered on the fovea were subdivided into 5 equidistant concentric rings (C1-C5). An automated algorithm was used to quantify the mean cone density (mCD; cells/mm2). Macular MVDs (%) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were assessed by OCTA. Results: In the moderate RP group, CDs in C2 and C3 were each significantly lower than in the normal group (both P < 0.05). In the severe RP group, CDs were significantly lower than in normal eyes in each concentric ring (all P < 0.001; C1-C5). In both RP groups, MVDs were significantly lower than in normal eyes for both the SCP and DCP (both P < 0.05). The mean CD was significantly correlated with the MVD in the DCP (r = 0.43; P = 0.028) but not in the SCP (r = -0.19, P = 0.323). Conclusions: Decreased CD was present in the moderate and severe RP groups. This was accompanied by a decreased MVD in the DCP. Direct assessment of photoreceptors in RP patients by high-resolution imaging technologies is crucial for the future development of RP therapeutics.


Assuntos
Fóvea Central/irrigação sanguínea , Células Fotorreceptoras Retinianas Cones/patologia , Vasos Retinianos/patologia , Retinite Pigmentosa/fisiopatologia , Adolescente , Adulto , Idoso , Criança , Estudos Transversais , Feminino , Angiofluoresceinografia , Humanos , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Tomografia de Coerência Óptica
3.
Ophthalmic Surg Lasers Imaging Retina ; 50(11): 709-718, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755970

RESUMO

BACKGROUD AND OBJECTIVE: To evaluate the relationship between retinal microvascular parameters on optical coherence tomography angiography (OCTA) and neurodegenerative changes assessed by measurement of brain volume on volumetric magnetic resonance imaging (MRI) in Alzheimer's disease (AD) and mild cognitive impairment (MCI). PATIENTS AND METHODS: Sixteen subjects with AD and MCI underwent OCTA imaging (3 mm × 3 mm and 6 mm × 6 mm scans) and volumetric brain MRI imaging with automated volumetric segmentation and quantification. Spearman's correlation (ρ) was performed between forebrain parenchyma, cortical gray matter, inferolateral ventricle (ILV), lateral ventricle (LV), and hippocampus (HP) MRI volumes and vessel density (VD), along with perfusion density (PD) for the 6-mm circle, 6-mm ring, 3-mm circle, and 3-mm ring Early Treatment Diabetic Retinopathy Study regions of the superficial capillary plexus. RESULTS: Thirty eyes of 16 patients (seven MCI and nine AD) with good-quality OCTA images were analyzed. ILV volume inversely correlated with the VD in the 6-mm circle (ρ = -0 .565, P = .028) and 3-mm ring (ρ = -0.569, P = .027) and PD in the 3-mm ring (ρ = -0.605, P = .0169). Forebrain, cortical gray matter, LV, and HP volumes did not significantly correlate with either VD or PD (P > .05). CONCLUSIONS: In this pilot investigation, the authors found a significant correlation between reduction in the superficial capillary plexus VD and PD on OCTA and expansion of the ILV in MCI and AD. This relationship between the retinal microvasculature and cerebral volumetric changes deserves further investigation. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:709-718.].


Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Disfunção Cognitiva/patologia , Vasos Retinianos/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Angiofluoresceinografia/métodos , Humanos , Imagem por Ressonância Magnética , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Projetos Piloto , Fluxo Sanguíneo Regional , Tomografia de Coerência Óptica/métodos
4.
Life Sci ; 237: 116929, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610210

RESUMO

LncRNA small nucleolar RNA host gene 3 (Snhg3) has been involved in cell proliferation and migration in malignant cells. However, its role in regulating functions of non-malignant cells has been hardly reported. Here, we found Snhg3 expression was sharply induced in primary brain microvascular endothelial cells (BMVECs) treated with oxygen-and-glucose-deprivation (OGD) plus hemin, an in vitro model of intracerebral hemorrhage (ICH). Downregulation of Snhg3 by siRNA transfection improved cell proliferation and migration abilities and reduced cell apoptosis and monolayer permeability in BMVECs under treatment with OGD plus hemin. Snhg3 overexpression suppressed cell proliferation and migration and increased cell apoptosis and monolayer permeability under normal condition. In ICH rats, downregulation of Snhg3 by siRNA injection improved behavioral and histological manifestations, including number of right turns, limb placement score, integrity of blood-brain barrier (BBB), brain water content and cell apoptosis in vivo. In the mechanism exploration, we found that, TWEAK and Snhg3 displayed a positive correlation with each other. Snhg3 overexpression increased expression of TWEAK protein and its receptor Fn14, that were also induced by OGD plus hemin, activating the downstream neuroinflammatory pathway STAT3 and enhancing the secretion of MMP-2/9. Finally, the TWEAK-siRNA, the Fn14 inhibitor ATA and the STAT3 blocker AG490 were respectively used to treat BMVECs under treatment with OGD plus hemin. Our results showed either TWEAK downregulation, Fn14 inhibition, or STAT3 blockade, could rescue Snhg3-induced impairment of BMVEC functions. In conclusion, the lncRNA Snhg3 contributes to dysfunction of cerebral microvascular cells in ICH rats by activating the TWEAK/Fn14/STAT3 pathway.


Assuntos
Encéfalo/patologia , Hemorragia Cerebral/patologia , Citocina TWEAK/metabolismo , Endotélio Vascular/patologia , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Receptor de TWEAK/metabolismo , Animais , Comportamento Animal , Encéfalo/metabolismo , Células Cultivadas , Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Circulação Cerebrovascular/fisiologia , Citocina TWEAK/genética , Endotélio Vascular/metabolismo , Regulação da Expressão Gênica , Masculino , Microvasos/metabolismo , Microvasos/patologia , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/genética , Receptor de TWEAK/genética , Cicatrização
5.
Clin Exp Rheumatol ; 37 Suppl 119(4): 3-14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587697

RESUMO

Systemic sclerosis (SSc) is a complex disorder characterised by the involvement of small arteries, microvessels and connective tissue, with deposition of fibrotic tissue and microvascular obliteration in the skin and internal organs. Due to the multifaceted nature of the disease, several articles are published in the medical literature every year, aimed at exploring different aspects of the pathogenesis, internal organ involvement and clinical aspects, and possible therapeutic approaches. In this article we have reviewed the literature on SSc of the past year, with the aim of identifying novel approaches that may help the treating physician in the clinical management of patients.


Assuntos
Microvasos/patologia , Escleroderma Sistêmico , Vasos Sanguíneos/patologia , Fibrose , Humanos , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Pele
6.
Turk J Ophthalmol ; 49(5): 300-304, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31650815

RESUMO

Optic disc drusen (ODD) is an important clinical entity that is sometimes misdiagnosed as papilledema because of elevated and blurred disc margins. A 17-year-old male who presented with headaches underwent detailed ophthalmological examination as well as colored fundus photography, B-scan ultrasonography (USG), fundus autofluorescence (FAF), optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), and visual field testing. His visual acuity was 10/10 in both eyes. Fundus examination revealed bilateral blurred and elevated optic disc margins. Diagnosis of bilateral ODD was confirmed with B-scan USG. FAF imaging revealed hyperautofluorescent areas on both optic discs. Optic nerve head OCT scans showed elevated irregular disc borders and thinning of the retinal nerve fiber layer in both eyes. On visual field testing, loss of the nasal visual field was detected in the left eye. OCTA imaging showed focal capillary dropout, especially in the nasal peripapillary area, in both eyes and reduced peripapillary and macular vessel density. In this case report, we evaluated the clinical findings and the structural features of bilateral ODD with multimodal imaging modalities including OCTA.


Assuntos
Microvasos/patologia , Imagem Multimodal/métodos , Drusas do Disco Óptico/diagnóstico , Vasos Retinianos/patologia , Acuidade Visual , Campos Visuais , Adolescente , Angiofluoresceinografia/métodos , Fundo de Olho , Humanos , Masculino , Fibras Nervosas , Disco Óptico/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos
7.
J Surg Oncol ; 120(8): 1412-1419, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31621086

RESUMO

BACKGROUND: Anastomotic leakage (AL) is a serious complication after anterior resection. The purpose of this study was to determine the role of microvascular density (MVD) in AL and to develop a nomogram to accurately predict AL. METHODS: This study retrospectively enrolled 477 consecutive patients who underwent anterior resection for rectal cancer from January 2011 to January 2019. Tissue samples of the resection margins were assessed for MVD. Univariate and multivariate regression analyses were used to identify the risk factors for AL. RESULTS: The incidence of clinical AL was 6.7%. MVD in the distal margin was associated with AL (P < .001). Univariate and multivariate regression analysis identified the following variables as independent risk factors for AL: preoperative albumin ≤35 g/L (odds ratio [OR] = 2.511), neoadjuvant treatment (OR = 3.560), location of tumor ≤7 cm (OR = 3.381), blood loss ≥100 mL (OR = 2.717), and MVD in the distal margin ≤20 (OR = 4.265). Then, a nomogram including these predictors was developed. The nomogram showed good discrimination (AUC = 0.816) and calibration (concordance index = 0.816). The decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: MVD in the distal margin is closely associated with AL. The nomogram can be used for individualized prediction of AL after anterior resection for patients with rectal cancer.


Assuntos
Fístula Anastomótica/etiologia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Margens de Excisão , Nomogramas , Neoplasias Retais/irrigação sanguínea , Neoplasias Retais/cirurgia , Perda Sanguínea Cirúrgica , Feminino , Humanos , Masculino , Microcirculação , Microvasos/patologia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica
8.
Eur J Radiol ; 120: 108669, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542700

RESUMO

PURPOSE: DCE MRI is a functional imaging modality, which is widely acknowledged to be linked to microvessel density in tissues. Therefore, it might be able to predict vessels in tumors. The present study sought to elucidate possible associations between microvessel density and histogram parameters in head and neck squamous cell carcinomas (HNSCC). METHOD: 30 patients with histologically proven HNSCC were included in the study. DCE MRI was performed with a 3 T MRI and histogram analysis was calculated with a whole lesion measurement. In every case microvessel density was estimated with CD105 stained specimens. RESULTS: Median derived from Ktrans correlated with vessel area (ρ = 0.39, P = 0.034). No other Ktrans or Ve parameter reached statistically significance. Several Kep derived parameters correlated with vessel area as well as with vessel count. MinKep had the highest correlation coefficient with vessel area (ρ = 0.45, P = 0.01). ModeKep had the highest coefficient with vessel count (ρ = 0.41, P = 0.03). CONCLUSIONS: Histogram parameters derived from Kep might be used as surrogate imaging biomarkers for microvessel density parameters in HNSCC. MinimumKep showed the highest correlation with vessel area and Mode Kep with vessel count.


Assuntos
Neoplasias de Cabeça e Pescoço/irrigação sanguínea , Microvasos/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/irrigação sanguínea , Meios de Contraste , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
9.
Tumori ; 105(6): 494-500, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31478461

RESUMO

BACKGROUND: An integral and well-functioning vascular system is essential for tumor progression and chemotherapy infusion. However, the lumen integrity of the microvessels and its significance in prognosis has not been studied. In this study, we found that the proportion of collapsed microvessels is suggested to be a novel biomarker for predicting prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: In this study, immunohistochemical CD31 staining was performed to identify the microvessels in tumor specimens. Proportions of collapsed vessels were estimated in CD31-stained tumor specimens from 100 patients with NSCLC. The correlation between collapsed microvessel proportion and survival time were evaluated by univariate and multivariate analysis. RESULTS: Data from 99 patients were analyzed and a wide range of collapse-microvessel fraction was observed in 96 patients (1.4%-70%). Elevated collapse proportion (⩾6.5%) indicated poor overall survival in both univariate analysis (p = 0.042) and multivariate analysis (p = 0.014). CONCLUSIONS: Elevated proportion of collapsed microvessels indicted poor survival outcome in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Microvasos/patologia , Neovascularização Patológica , Adulto , Idoso , Biomarcadores Tumorais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
10.
J Dtsch Dermatol Ges ; 17(9): 895-904, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31487114

RESUMO

AIMS: The classifications of occluding vasculopathies may present some difficulties. Firstly, classifications may follow different principles, e.g. clinicopathological findings, etiology or pathomechanism. Secondly, authors sometimes do not distinguish between vasculitis and vasculopathy. Thirdly, vasculopathies are often systemic diseases. Organ-specific variations make morphologic findings difficult to compare. Moreover, subtle changes may be recognized in the skin, but be invisible in other organs. Our aim was to use the skin and subcutis as tools and clinicopathological correlation as the basic process for classification. METHODS AND RESULTS: In the first step, we differentiate between small and medium vessel occluding vasculopathies in the skin, and focus in this part on small vessel occluding vasculopathies. In the second step, we differentiate among subtypes of small vessels. In the final step, we differentiate according to the time point of the coagulation/reorganization process and the involved inflammatory cells/stromal features. Applying the same procedure to the various entities and visualizing the findings with bar codes makes the similarities and differences more apparent, both clinically and with histopathology. CONCLUSION: Occluding vasculopathies are often not separate entities, but reaction patterns and epiphenomena. Distinguishing them from vasculitides is crucial because of differences in pathogenesis, therapeutic approach and prognosis.


Assuntos
Algoritmos , Processamento Eletrônico de Dados , Dermatopatias Vasculares/patologia , Vasculite/patologia , Anticoagulantes/efeitos adversos , Constrição Patológica/patologia , Diagnóstico Diferencial , Humanos , Livedo Reticular/classificação , Microvasos/patologia , Necrose/induzido quimicamente , Dermatopatias Bacterianas/patologia
11.
Diabetes Res Clin Pract ; 157: 107870, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31560961

RESUMO

AIMS: To assess the risk of macrovascular complications in patients developing diabetes from statin treatment. METHODS: In this population-based cohort study, 40,409 participants who began to receive statin therapy between 2000 and 2012 were enrolled in to the study group, and another 1:1 matched adults without statin treatment during the same period served as the control group. Both groups were followed up to identify individuals who later developed diabetes. After a follow-up identification of diabetes, diabetes and non-diabetes cohorts were subjected to an analysis for the risk of macrovascular events between diagnosis of diabetes and December 31, 2013. RESULTS: Compared with individuals without statin therapy, statin-treated patients had a higher risk of developing diabetes (adjusted hazard ratio: 2.46; 95% confidence interval: 2.37-2.57). Compared with statin-treated patients without diabetes, statin-treated participants developing diabetes had a higher overall incidence of macrovascular complications (adjusted hazard ratio: 1.74; 95% confidence interval: 1.62-1.88). Moreover, compared with that of other diabetogenic statins, patients taking pravastatin had a lower risk of developing diabetes (adjusted hazard ratio: 0.63; 95% confidence interval: 0.55-0.73) and macrovascular events (adjusted hazard ratio: 0.64; 95% confidence interval: 0.42-0.98). CONCLUSIONS: According to these findings, prescribing statins that have a neutral effect on glucose homeostasis may be advisable for Asian populations.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Microvasos/patologia , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Risco
12.
Neuron ; 103(3): 367-379, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394062

RESUMO

Traumatic brain injury (TBI) is one the most common human afflictions, contributing to long-term disability in survivors. Emerging data indicate that functional improvement or deterioration can occur years after TBI. In this regard, TBI is recognized as risk factor for late-life neurodegenerative disorders. TBI encompasses a heterogeneous disease process in which diverse injury subtypes and multiple molecular mechanisms overlap. To develop precision medicine approaches where specific pathobiological processes are targeted by mechanistically appropriate therapies, techniques to identify and measure these subtypes are needed. Traumatic microvascular injury is a common but relatively understudied TBI endophenotype. In this review, we describe evidence of microvascular dysfunction in human and animal TBI, explore the role of vascular dysfunction in neurodegenerative disease, and discuss potential opportunities for vascular-directed therapies in ameliorating TBI-related neurodegeneration. We discuss the therapeutic potential of vascular-directed therapies in TBI and the use and limitations of preclinical models to explore these therapies.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Circulação Cerebrovascular , Microvasos/patologia , Doenças Neurodegenerativas/etiologia , Acoplamento Neurovascular , Animais , Barreira Hematoencefálica , Lesões Encefálicas Traumáticas/fisiopatologia , Isquemia Encefálica/etiologia , Progressão da Doença , Endotélio Vascular/fisiopatologia , Humanos , Microcirculação , Micronutrientes/farmacocinética , Modelos Animais , Proteínas do Tecido Nervoso/metabolismo , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/prevenção & controle , Neuroimagem
13.
BMC Gastroenterol ; 19(1): 146, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420015

RESUMO

BACKGROUND: Microvessel density (MVD), as a derived marker for angiogenesis, has been associated with poor outcome in several types of cancer. This study aimed to evaluate the prognostic value of MVD in stage II and III colon cancer and its relation to tumour-stroma-percentage (TSP) and expression of HIF1A and VEGFA. METHODS: Formalin-fixed paraffin-embedded (FFPE) colon cancer tissues were collected from 53 stage II and 54 (5-fluorouracil-treated) stage III patients. MVD was scored by digital morphometric analysis of CD31-stained whole tumour sections. TSP was scored using haematoxylin-eosin stained slides. Protein expression of HIF1A and VEGFA was determined by immunohistochemical evaluation of tissue microarrays. RESULTS: Median MVD was higher in stage III compared to stage II colon cancers (11.1% versus 5.6% CD31-positive tissue area, p < 0.001). High MVD in stage II patients tended to be associated with poor disease free survival (DFS) in univariate analysis (p = 0.056). In contrast, high MVD in 5FU-treated stage III patients was associated with better DFS (p = 0.006). Prognostic value for MVD was observed in multivariate analyses for both cancer stages. CONCLUSIONS: MVD is an independent prognostic factor associated with poor DFS in stage II colon cancer patients, and with better DFS in stage III colon cancer patients treated with adjuvant chemotherapy.


Assuntos
Quimioterapia Adjuvante/métodos , Neoplasias do Colo , Microvasos , Neovascularização Patológica , Colo/patologia , Neoplasias do Colo/irrigação sanguínea , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Densitometria/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imuno-Histoquímica , Masculino , Microvasos/diagnóstico por imagem , Microvasos/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/etiologia , Países Baixos , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos
14.
Biomed Res Int ; 2019: 9264137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428651

RESUMO

Background: Numerous studies have shown that hepatocellular carcinoma (HCC) without microvascular invasion (MVI) may have better outcomes. This study established a preoperative MVI risk nomogram mainly incorporating three related risk factors of MVI in BCLC 0/A HCC after surgery. Methods: Independent predictors for the risk of MVI were investigated, and an MVI risk nomogram was established based on 60 patients in the training group who underwent curative hepatectomy for BCLC 0/A HCC and validated using a dataset in the validation group. Results: Univariate analysis in the training group showed that hepatitis viral B (HBV) DNA (P=0.034), tumor size (P<0.001), CT value in the venous phase (P=0.039), CT value in the delayed phase (P=0.017), peritumoral enhancement (P=0.013), visible small blood vessels in the arterial phase (P=0.002), and distance from the tumor to the inferior vena cava (IVC) (DTI, P=0.004) were risk factors significantly associated with the presence of MVI. According to multivariate analysis, the independent predictive factors of MVI, including tumor size (P=0.002), CT value in the delayed phase (P=0.018), and peritumoral enhancement (P=0.057), were incorporated in the corresponding nomogram. The nomogram displayed an unadjusted C-index of 0.851 and a bootstrap-corrected C-index of 0.832. Calibration curves also showed good agreement on the presence of MVI. ROC curve analyses showed that the nomogram had a large AUC (0.851). Conclusions: The proposed nomogram consisting of tumor size, CT value in the delayed phase, and peritumoral enhancement was associated with MVI risk in BCLC 0/A HCC following curative hepatectomy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Microvasos , Neovascularização Patológica , Nomogramas , Adulto , Idoso , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Microvasos/patologia , Microvasos/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica , Neovascularização Patológica/patologia , Neovascularização Patológica/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco
15.
Nanoscale ; 11(33): 15537-15549, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31393488

RESUMO

Inhaled atmospheric nanoparticles (ANPs) can migrate into human blood vessels. However, the exact pathogenesis has not yet been well elucidated. In this study, a perfusable 3D human microvessel network was constructed in a microfluidic device. This functional 3D micro-tissue partly mimicked the physiological response of human vessels. Intravascular nanoparticles tend to adsorb proteins to form a protein corona. Based on this pathological response, vessel permeability and vasoconstriction resulting from ANP stimulation might be related to vascular inflammation. It mediated abnormal expression of nuclear factor-κB (NF-κB) and an influx of intracellular Ca2+ ([Ca2+]i). This biological behavior disturbed the normal expression of intercellular cell adhesion molecule 1 (ICAM-1) and vascular endothelial growth factor (VEGF). The imbalance of nitric oxide (NO) and endothelin-1 (ET-1) further resulted in endothelial cell contraction. All these bio-events induced the loss of tight junctions (ZO-1) which enhanced vessel permeability. Meanwhile, ANP induced-vascular toxicity was also found in mice. Our observations provide a plausible explanation for how the ANPs affect human vascular function. The vessel-on-chip provides a bridge between in vitro results and human responses. We aimed to use this human 3D functional microvascular model to mimic the physiological responses of human vessels. This model is suitable for the evaluation of vascular toxicity after the human vessel exposure to ANPs.


Assuntos
Dispositivos Lab-On-A-Chip , Microvasos/química , Modelos Cardiovasculares , Nanopartículas/química , Animais , Cálcio/metabolismo , Técnicas de Cultura de Células , Células Endoteliais da Veia Umbilical Humana , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Microvasos/patologia , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Coroa de Proteína/química , Engenharia Tecidual , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
16.
Int J Mol Sci ; 20(15)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362427

RESUMO

Amplification of oxidative stress is present since the early stages of chronic kidney disease (CKD), holding a key position in the pathogenesis of renal failure. Induction of renal pro-oxidant enzymes with excess generation of reactive oxygen species (ROS) and accumulation of dityrosine-containing protein products produced during oxidative stress (advanced oxidation protein products-AOPPs) have been directly linked to podocyte damage, proteinuria, and the development of focal segmental glomerulosclerosis (FSGS) as well as tubulointerstitial fibrosis. Vascular oxidative stress is considered to play a critical role in CKD progression, and ROS are potential mediators of the impaired myogenic responses of afferent renal arterioles in CKD and impaired renal autoregulation. Both oxidative stress and inflammation are CKD hallmarks. Oxidative stress promotes inflammation via formation of proinflammatory oxidized lipids or AOPPs, whereas activation of nuclear factor κB transcription factor in the pro-oxidant milieu promotes the expression of proinflammatory cytokines and recruitment of proinflammatory cells. Accumulating evidence implicates oxidative stress in various clinical models of CKD, including diabetic nephropathy, IgA nephropathy, polycystic kidney disease as well as the cardiorenal syndrome. The scope of this review is to tackle the issue of oxidative stress in CKD in a holistic manner so as to provide a future framework for potential interventions.


Assuntos
Estresse Oxidativo , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/metabolismo , Albuminúria/etiologia , Albuminúria/metabolismo , Animais , Biomarcadores , Gerenciamento Clínico , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Humanos , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Microvasos/metabolismo , Microvasos/patologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia
17.
Biochimie ; 165: 141-149, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31365884

RESUMO

MicroRNA-25-5p (miR-25-5p) may be involved in the pathogenesis and processes of vascular diseases. The aim of this study was to investigate the role of miR-25-5p in oxidized low-density lipoprotein (ox-LDL)-treated human brain microvessel endothelial cells (HBMECs) and the underlying mechanisms. RT-qPCR and/or Western blot were used to detect the expression levels of miR-25-5p and neuronal growth regulator 1 (NEGR1). The effect of miR-25-5p overexpression and NEGR1 silencing on cell proliferation, migration, apoptosis and reactive oxygen species (ROS) production of HBMECs were measured by using CCK-8 assay, transwell assay and flow cytometry, respectively. The expression levels of apoptosis-related protein (cleaved caspase-3 and pro-caspase-3) were detected using Western blot, and the nitric oxide (NO) production was measured by a nitric oxide assay kit. The expression level of miR-25-5p was decreased in HBMECs treated with ox-LDL. Compared with the control group, miR-25-5p overexpression significantly promoted the proliferation and migration of HBMECs treated with ox-LDL (p < 0.01). Overexpression of miR-25-5p significantly suppressed cell apoptosis, ROS production and NO reduction of ox-LDL-induced HBMECs (p < 0.01). In addition, the target gene of miR-25-5p was predicted to be NEGR1 through Targetscan online analysis. The effect of NEGR1 silencing on cell proliferation, migration, apoptosis, ROS and NO production of ox-LDL-induced HBMECs was similar to that of miR-25-5p overexpression. Furthermore, miR-25-5p overexpression and NEGR1 silencing significantly downregulated the protein expression levels of JAK2 and STAT3. Thus, miR-25-5p neutralizes the effects of ox-LDL on multiple functions of HBMECs through suppressing the expression of NEGR1 via regulating the JAK/STA signaling pathway.


Assuntos
Encéfalo/irrigação sanguínea , Moléculas de Adesão Celular Neuronais/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Lipoproteínas LDL/metabolismo , MicroRNAs/fisiologia , Apoptose , Linhagem Celular , Movimento Celular , Proliferação de Células , Proteínas Ligadas por GPI/metabolismo , Humanos , Janus Quinase 2/metabolismo , Microvasos/patologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
18.
Diagn Interv Radiol ; 25(5): 331-337, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31287429

RESUMO

PURPOSE: Progression of liver fibrosis to end-stage disease can potentially be prevented with antiviral treatment. Thus, diagnosis of fibrosis is important in determining treatment protocols. This study aims first, to determine the sensitivity of a novel Doppler method, superb microvascular imaging (SMI), in detecting small vascular structures of the liver compared with other Doppler methods; and second, to choose the best method among these Doppler applications to determine the morphologic changes that occur due to chronic fibrosis. By doing so, the study would be able to provide an ultrasound grading that might differentiate and predict mild and severe liver fibrosis, thus giving rise to a possible alternative to biopsy. METHODS: A total of 43 patients diagnosed with chronic hepatitis and scheduled for liver biopsy were included. Color Doppler, power Doppler, advanced dynamic flow (ADF) Doppler, color SMI (cSMI) and monochrome SMI (mSMI) Doppler were performed in subcapsular areas of right anterior lobe. Depth from the capsule of the most peripherally located detectable vessel was measured for each Doppler subgroup. Appearance of the vascular tree was categorized into four groups and correlated with pathology results. ROC curve analysis was used to determine if this Doppler classification was statistically significant in differentiating mild and severe forms of fibrosis. Finally, multiple regression analysis was used to determine which Doppler parameter can significantly predict severity. RESULTS: mSMI and cSMI were found to be superior to other Doppler techniques in detecting the most superficially located vessels of the liver, 4.4 mm and 3.3 mm deep from the capsule, respectively (P < 0.001). Among the changes identified in the vascular tree, small vessel blunting was the most prevalent finding in predicting the presence of severe fibrosis (multiple regression test, t=5.969, P < 0.0001). ROC analysis identified that the presence of at least two pathologic findings in the vascular tree was highly predictive of severe fibrosis (AUC=0.881, sensitivity 86.67%, specificity 89.29%, positive and negative predictive values 8.09 and 0.15, respectively). CONCLUSION: Our study proves that SMI is superior to other Doppler techniques in detecting the smallest vessels visible to ultrasound. Using this method, it is possible to determine the vascular changes in terms of blunting and tortuosity and thus predict the severity of fibrosis. This method might be a practical alternative to biopsy.


Assuntos
Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Microvasos/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Adulto , Idoso , Feminino , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença
19.
Int J Oncol ; 55(3): 657-670, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322171

RESUMO

Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer after hepatocellular carcinoma. Antiangiogenic therapy has been administered to patients with CCA, but the benefits of this therapy remain unsatisfactory. Improved understanding of the molecular mechanisms underlying angiogenesis in CCA is required. In the present study, the expression of GATA­binding protein 6 (GATA6), lysyl oxidase­like 2 (LOXL2) and vascular endothelial growth factor A (VEGFA), in addition to the microvessel density (MVD), were evaluated by performing immunohistochemical staining of human CCA microarrays. The expression of GATA6/LOXL2 was associated with poor overall survival (P=0.01) and disease­free survival (P=0.02), and was positively associated with VEGFA expression (P=0.02) and MVD (P=0.04). In vitro, western blotting, reverse transcription­quantitative PCR analysis and ELISAs revealed that altered GATA6 and LOXL2 expression regulated the expression levels of secreted VEGFA. Co­immunoprecipitation demonstrated a physical interaction between GATA6 and LOXL2 in CCA cell lines, and the scavenger receptor cysteine­rich domain of LOXL2 interacted with GATA6, which regulated VEGFA mRNA expression and protein secretion, and promoted tube formation. In vivo analyses further revealed that GATA6/LOXL2 promoted VEGFA expression, angiogenesis and tumor growth. The GATA6/LOXL2 complex represents a novel candidate prognostic marker for stratifying patients with CCA. Drugs targeting this complex may possess great therapeutic value in the treatment of CCA.


Assuntos
Aminoácido Oxirredutases/metabolismo , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Fator de Transcrição GATA6/metabolismo , Microvasos/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Aminoácido Oxirredutases/genética , Animais , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Feminino , Fator de Transcrição GATA6/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Microvasos/metabolismo , Pessoa de Meia-Idade , Neoplasias Experimentais , Prognóstico , Transdução de Sinais , Análise de Sobrevida , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/química , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
PLoS One ; 14(7): e0220146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31329636

RESUMO

Microvascular proliferation (MVP), an aberrant vascular structure containing multilayered mitotically active endothelial- and smooth-muscle cells/pericytes, is a histopathological hallmark of glioblastoma multiforme (GBM). Although MVP tends to be associated with high-grade glioma, it has also been detected in WHO grade I pilocytic astrocytoma (PA). However, little is known about the mechanism underlying its formation. Using TP53 point mutations as a marker for tumor-derived cells, we earlier reported that MVP was partially converted from tumor cells via mesenchymal transition. In the current study we used the KIAA1549-BRAF fusion gene as a marker to assess whether MVPs in PA contained tumor-derived cells and/or phenotypically distinct tumor cells expressing vascular markers. cDNA synthesized from frozen tissue of six PA patients operated at our institute was analyzed to detect the KIAA1549-BRAF fusion gene by reverse transcription polymerase chain reaction (RT-PCR) assay. The breakpoint in the fusion gene was identified by long and accurate PCR (LA-PCR) and Sanger sequencing of genomic DNA. Distinct tumor cells and cellular components of MVP were obtained by laser microdissection. For the qualitative and quantitative detection of the KIAA1549-BRAF fusion gene we performed genomic and digital PCR assays. Fluorescence in situ hybridization (FISH) was used to assess gene fusion in cellular components of MVP. Samples from three PA patients harbored the KIAA1549 exon 15, BRAF exon 9 fusion gene. In two patient samples with abundant MVP, RT-PCR assay detected strong bands arising from the KIAA1549-BRAF fusion gene in both tumor cells and cellular components of MVP. Digital PCR showed that vis-à-vis tumor tissue, its relative expression in cellular components of MVP was 42% in one- and 76% in another sample. FISH revealed amplified signals in both tumor cells and cellular components of MVP indicative of tandem duplication. Our findings suggest that in patients with PA, some cellular components of MVP contained tumor derived cell and/or phenotypically distinct tumor cells expressing vascular markers.


Assuntos
Astrocitoma/genética , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Microvasos/metabolismo , Proteínas de Fusão Oncogênica/genética , Adolescente , Adulto , Astrocitoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Humanos , Masculino , Microvasos/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Proteínas de Fusão Oncogênica/metabolismo
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