RESUMO
Invasion, metastasis, and recurrence are the most common causes of death in patients with hepatocellular carcinoma (HCC) and are therefore critical factors for both therapy and prognosis. Current methods for diagnosis of HCC rely mainly on serological markers such as alpha-fetoprotein and liver enzymes, together with physical assessment and imaging techniques. The availability of more accurate serum markers may facilitate screening and early diagnosis, which will improve prognosis. This retrospective cohort analysis included 50 consecutive patients with cirrhosis and single or multifocal HCC and 40 control subjects with no liver disease or risk factors for viral hepatitis. Expression of epidermal growth factor-like domain 7 (EGFL7), osteopontin (OPN), and prostaglandin E2 (PGE2) were detected using an enzyme-linked immunosorbent assay. The mean serum levels of EGFL7, OPN, and PGE2 in the HCC group were 132.11 pg/mL, 11.77 ng/mL, and 179.37 pg/mL, respectively, which were all significantly higher than the levels in the control group (23.03 pg/mL, 2.31 ng/mL, and 47.36 pg/mL, respectively; P < 0.001). Serum levels of EGFL7, OPN, and PGE2 levels may thus be useful for screening and surveillance of HCC among high-risk populations, and have the potential to improve prognosis of these patients.
Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Adulto , Idoso , Biomarcadores Tumorais/sangue , Proteínas de Ligação ao Cálcio , Dinoprostona/sangue , Família de Proteínas EGF , Fatores de Crescimento Endotelial/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Fibrose/sangue , Perfilação da Expressão Gênica , Marcadores Genéticos/genética , Humanos , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Recidiva Local de Neoplasia , Osteopontina/sangue , Prognóstico , Estudos Retrospectivos , Fatores de Risco , alfa-Fetoproteínas/metabolismoRESUMO
PURPOSE: This study focused on circulating levels of vascular endothelial growth factor in patients with prostate cancer compared to a normal population. METHODS: We analyzed 26 normal individuals and 80 patients with prostate cancer. Blood was drawn from all subjects, and plasma was extracted to determine the concentration of vascular endothelial growth factor using a quantitative immunoassay technique (ELISA-enzyme-linked immunosorbent assay). RESULTS: The median plasma level of vascular endothelial growth factor was significantly elevated in patients with metastatic disease compared to patients with localized disease and with healthy controls. Patients with serum prostate-specific antigen > 20 ng/mL had significantly higher levels of plasma vascular endothelial growth factor than patients with serum prostate-specific antigen < 20 ng/mL. There was a trend for patients with a Gleason score of 8 to 10 to have higher levels of plasma vascular endothelial growth factor when compared to patients with lower Gleason scores. No relationship was found between plasma vascular endothelial growth factor and clinical staging, or between plasma vascular endothelial growth factor and prostate volume, in patients with localized prostate cancer. CONCLUSION: This study indicates that patients with metastatic prostate cancer have higher plasma vascular endothelial growth factor levels than patients with localized disease or in healthy controls.
OBJETIVO: Analisar os níveis circulantes do fator de crescimento do endotélio vascular em pacientes com câncer prostático comparados com uma população de indivíduos eutróficos. MÉTODOS: Vinte e seis indivíduos eutróficos e oitenta pacientes com câncer de próstata foram analisados nesse estudo. A coleta sangüínea foi realizada da mesma maneira em todos os pacientes e o plasma foi extraído para a determinação dos níveis do fator de crescimento do endotélio vascular, utilizando-se o método quantitativo ELISA (enzyme-linked immunosorbent assay). RESULTADOS: Os níveis de fator de crescimento do endotélio vascular plasmático encontraram-se significativamente elevados nos pacientes com doença metastática quando comparados com pacientes com doença localizada e com indivíduos sadios. Pacientes com PSA sérico maior que 20 ng/ml apresentaram níveis maiores de fator de crescimento do endotélio vascular plasmático quando comparados com pacientes com PSA menor que 20 ng/ml. Houve uma tendência dos pacientes com escore de Gleason de 8 a 10 apresentarem níveis maiores do fator de crescimento do endotélio vascular plasmático em relação a pacientes com escores de Gleason menores que 8. Não houve relação entre fator de crescimento do endotélio vascular plasmático e estado clínico, ou entre fator de crescimento do endotélio vascular e volume prostático em pacientes com câncer de próstata localizado. CONCLUSÃO: Os dados indicam que pacientes com câncer de próstata metastático apresentam níveis significativamente mais elevados de fator de crescimento do endotélio vascular plasmático quando comparados com pacientes com câncer localizado e com indivíduos normais.
Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Fatores de Crescimento Endotelial/sangue , Estadiamento de Neoplasias/métodos , Tamanho do Órgão/fisiologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Biomarcadores Tumorais/sangue , Distribuição por Idade , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Metástase Neoplásica , Prognóstico , Próstata/patologia , Neoplasias da Próstata/classificação , Neoplasias da Próstata/patologia , Estatísticas não ParamétricasRESUMO
En las últimas décadas la medicina evolucionó hacia un enfoque molecular en la búsqueda de blancos específicos que permitan seguir adecuadamente la progresión de las patologías neoplásicas y desarrollar terapias exitosas. El conocimiento y comprensión de que la matriz extracelular (MEC) que rodea a un tumor influye sobre el comportamiento del mismo, reveló la importancia que cumplen las metaloproteinasas (MMPs) en la regulación de los componentes de la MEC, y por lo tanto en el desarrollo tumoral. Es por ello que actualmente se está evaluando la eficacia de inhibidores sintéticos de estas enzimas en ensayos clínicos, algunos ya en fase clínica III de investigación. También se propone que estas MMPs podrían ser utilizadas como marcadores bioquímicos, permitiendo evaluar la progresión de la enfermedad en pacientes que sufren patologías neoplásicas, e incluso dar un valor pronóstico. Es en este punto en que el laboratorio de análisis clínicos cumplirá un papel fundamental y deberá contar con los conocimientos y las herramientas necesarias para evaluar la presencia y actividad de estas enzimas. En este trabajo se expone el conocimiento actual de la estructura y funciones biológicas de las MMPs así como los antecedentes que muestran el papel que cumplen en las enfermedades neoplásicas, en especial en leucemias y linfomas (AU)
Assuntos
Humanos , Biomarcadores Tumorais , Neoplasias/fisiopatologia , Neoplasias Experimentais/fisiopatologia , Leucemia/fisiopatologia , Linfoma/fisiopatologia , Neovascularização Patológica/etiologia , Fatores de Crescimento Endotelial/sangue , Neoplasias/enzimologia , Neoplasias/irrigação sanguínea , Neoplasias Experimentais/enzimologia , Leucemia/enzimologia , Linfoma/enzimologia , Progressão da Doença , Neovascularização Patológica/fisiopatologia , Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/fisiopatologia , Transtornos Linfoproliferativos , Metástase Neoplásica/fisiopatologiaRESUMO
OBJECTIVE: To investigate whether a polymorphism in the CD14 gene is associated with Kawasaki disease (KD). STUDY DESIGN: We extracted DNA from the whole blood of 69 control children and 67 patients with KD. We determined a polymorphism in the CD14 gene at position -159 upstream from the major transcription site (CD14/-159) by restriction fragment assay. We then investigated the association between CD14/-159 and the onset of KD and development of coronary artery lesion (CAL). RESULTS: The genomic and allelic frequencies of the polymorphism were not different between normal children and KD patients. The KD patients with TT genotypes at CD14/-159 had more CAL complications than those with CT and CC (OR, 4.05; 95% CI, 1.34-12.22). The frequencies of the T allele was significantly higher than that of the C allele in KD patients with CAL (OR, 2.20; 95% CI, 1.23-3.94). Their data were confirmed in the patients whether the patients were treated with intravenous gamma-globulin. KD patients with TT genotypes had significantly higher levels of C-reactive protein and vascular endothelial growth factor, which had previously been reported as risk factors for CAL, than those with CC genotypes. CONCLUSION: These results indicate that the T allele and TT genotype at CD14/-159 are risk factors for CAL in KD, and that the development of CAL in KD may be related to the magnitude of CD14 toll-like receptor response.
Assuntos
Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/genética , Receptores de Lipopolissacarídeos/genética , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Antineoplásicos/sangue , Pré-Escolar , Doença da Artéria Coronariana/sangue , Fatores de Crescimento Endotelial/sangue , Feminino , Genótipo , Fator de Crescimento de Hepatócito/sangue , Humanos , Receptores de Lipopolissacarídeos/sangue , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Fator de Necrose Tumoral alfa/análise , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
BACKGROUND: It has been speculated that increased levels of circulating or intraperitoneal pro-inflammatory cytokines such as interleukin 6, and pro-angiogenic vascular endothelial growth factor (VEGF) may contribute to high peritoneal small-solute transport rate (PSTR) in continuous ambulatory peritoneal dialysis (CAPD) patients. In this study we evaluated possible relationships between plasma and dialysate IL-6 and VEGF levels and PSTR. METHODS: Forty CAPD patients (mean age+/-SD of 58+/-14 years) with no apparent inflammation process or disease, who had been on CAPD for 19+/-15 months (range 3-56 months) were included in the study. Peritoneal equilibration test (PET) was used to evaluate PSTR. Patients were divided into two groups: high-average and high transporters (H/A; D/P(creat)>/=0.65) and low-average and low transporters (L/A; D/P(creat)<0.64). Albumin and IgG clearances were used in the evaluation of permeability to larger solutes. Plasma and overnight dialysate levels of IL-6 and VEGF were measured. RESULTS: Plasma IL-6 (7.6 vs 4.3 pg/ml) and VEGF (342 vs 163 pg/ml) as well as dialysate IL-6 (174 vs 80 pg/ml) and VEGF (96 vs 69 pg/ml) levels were significantly higher in the H/A than in the L/A group. The dialysate appearance of IL-6 and VEGF correlated with D/P(creat), as well as with albumin and IgG clearances. Moreover, significant correlations were noted between dialysate IL-6 and dialysate VEGF levels. CONCLUSIONS: The findings of (i) increased plasma and dialysate levels of IL-6 and VEGF in the H/A group compared to the L/A group, (ii) an association between PSTR and both plasma and dialysate IL-6 and VEGF levels, and (iii) a significant correlation between dialysate IL-6 and VEGF concentrations suggest that inflammation, angiogenesis, and peritoneal transport may be interrelated and involved in the pathophysiology of high PSTR in CAPD patients. However, due to the cross-sectional design of this study, the cause and effect relationships between plasma and dialysate IL-6 and VEGF concentrations and high PSRT remain unclear.
Assuntos
Fatores de Crescimento Endotelial/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Interleucina-6/sangue , Linfocinas/sangue , Diálise Peritoneal Ambulatorial Contínua , Creatinina/sangue , Citocinas/sangue , Feminino , Glomerulonefrite/sangue , Glomerulonefrite/imunologia , Glomerulonefrite/terapia , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Cavidade Peritoneal , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
The objective of this study was to assess the possible role of vascular endothelial growth factor (VEGF) in the pathogenesis of systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (PAPS). We studied 28 patients with SLE, 10 patients with PAPS, and 24 healthy controls. VEGF plasma levels were measured by ELISA. Immunolocalization of VEGF was done in renal tissue from SLE patients and cadaveric controls. Our results showed that VEGF plasma levels were increased in SLE patients compared with PAPS and controls. The correlation between clinical manifestations and VEGF levels revealed that SLE patients with renal failure had significantly increased plasma VEGF levels (134.1 + 91.0 pg/ml) compared with SLE patients with normal renal function (42.9 + 19.0 pg/ml), PAPS patients (41.9 + 26.6 pg/ml), and controls (36.2 + 27.0 pg/ml; P < 0.01). Immunostaining showed a strong expression of VEGF in SLE renal tissue samples. Our preliminary results indicate that VEGF is increased in plasma from patients with lupus nephritis and a moderate degree of renal failure and is overexpressed in renal tissue from these patients.
Assuntos
Síndrome Antifosfolipídica/sangue , Fatores de Crescimento Endotelial/sangue , Nefrite Lúpica/sangue , Linfocinas/sangue , Adulto , Síndrome Antifosfolipídica/patologia , Fatores de Crescimento Endotelial/análise , Feminino , Humanos , Rim/química , Rim/patologia , Nefrite Lúpica/patologia , Linfocinas/análise , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Tumor markers have been investigated in differentiation of benign and malignant tumors. We analyzed CA 125 and vascular endothelial growth factor (VEGF) levels in serum and cyst fluid in patients with epithelial ovarian tumors. Serum and tumor cyst fluid of 50 patients with ovarian epithelial tumors (7 malignant, 3 bordeline and 40 benign) were assayed for VEGF by ELISA and CA 125 levels by chemoluminescence. CA 125 serum levels were significantly higher in patients with malignant and borderline tumors than in patients with benign cysts (p = 0.0005). CA 125 cyst fluid contents were comparable for malignant, borderline and benign ovarian tumors (p = 0.39). Significantly higher levels of VEGF were present in cyst fluid for malignant and borderline tumors compared with benign cysts (p < 0.0001); however, serum levels of VEGF were similar among all patients (p = 0.25). The CA 125 serum levels correlated with matched VEGF cyst fluid levels (r = 0.44, p = 0.0015). Serum CA 125 and cystic VEGF were good methods to differentiate benign and malignant epithelial ovarian tumors. Patients with elevated intracystic VEGF levels presented significantly higher CA 125 serum levels, although the CA 125 intracystic content overlapped. The angiogenesis and enhancement of vascular permeability induced by VEGF represents a new hypothesis for the release of the CA 125 antigen into the circulation in patients with ovarian epithelial neoplasm.
Assuntos
Biomarcadores Tumorais/metabolismo , Antígeno Ca-125/metabolismo , Carcinoma/diagnóstico , Fatores de Crescimento Endotelial/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Linfocinas/metabolismo , Neoplasias Ovarianas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Carcinoma/sangue , Líquido Cístico/metabolismo , Fatores de Crescimento Endotelial/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Medições Luminescentes , Linfocinas/sangue , Pessoa de Meia-Idade , Cistos Ovarianos/metabolismo , Neoplasias Ovarianas/sangue , Valor Preditivo dos Testes , Curva ROC , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Distal extremity swelling with pitting oedema due to altered lymphatic drainage has been reported in some patients with rheumatoid arthritis (RA). The resistant-to-therapy oedema usually affected the upper limbs in an asymmetrical pattern. Until now, extensor tenosynovial involvement has not been described in RA patients suffering from distal extremity swelling with pitting oedema. Three patients are described: two of them had predominant extensor tenosynovial involvement in their hands, with impaired lymphatic drainage demonstrated by (MRI) and lymphoscintigraphy, respectively. In both cases the oedema was chronic and not responsive to treatment. One patient had extensor tenosynovial involvement without impaired lymphatic drainage. In this case, the oedema remitted completely after a few days of corticosteroid therapy. None of them showed differences in serum levels of vascular endothelial growth factor (VEGF), whether they were RA patients with no pitting oedema or healthy volunteers.
Assuntos
Artrite Reumatoide/fisiopatologia , Edema/diagnóstico , Edema/etiologia , Extremidades/patologia , Idoso , Idoso de 80 Anos ou mais , Fatores de Crescimento Endotelial/sangue , Feminino , Mãos/diagnóstico por imagem , Mãos/patologia , Humanos , Linfocinas/sangue , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Radiografia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
OBJECTIVES: To investigate the serum levels of VEGF in patients with rheumatoid arthritis of long duration. METHODS: Serum VEGF levels were measured in 118 patients with long-standing rheumatoid arthritis according to the ACR criteria (mean duration 12 years). The disease activity score was evaluated by the method of van der Heijde et al. RESULTS: Serum levels of VEGF in patients with RA were significantly higher than in healthy controls. VEGF levels showed no correlation with CRP, SAA amyloid protein, or the disease activity score. CONCLUSIONS: Our findings suggest that, contrary to the results reported in patients with early onset RA, where VEGF appears to play an active part in joint inflammation, in long-standing RA elevated VEGF serum levels may be an independent marker although its significance remain to be established.
Assuntos
Artrite Reumatoide/sangue , Fatores de Crescimento Endotelial/sangue , Linfocinas/sangue , Adulto , Amiloide/sangue , Artrite Reumatoide/fisiopatologia , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
OBJECTIVE: Hypertrophic osteoarthropathy (HOA) is characterized by the coexistence of digital clubbing and periosteal proliferation of the tubular bones. Localized vascular proliferation associated with platelet/endothelial cell activation are recognized features of this syndrome. Current knowledge suggests that HOA develops from the presence in the systemic circulation of one or more growth factors that are normally inactivated in the lungs. The nature of these purported growth factors has not yet been identified. Vascular endothelial growth factor (VEGF) has several features that may fit in with the pathogenesis of HOA. The objective of our study was to measure serum and plasma levels of VEGF in different groups of patients with HOA. METHODS: We studied 24 patients with HOA; of these, in 12 the HOA was secondary to cyanotic congenital heart disease and in 7 to lung cancer, while 5 represented primary cases. As controls we studied 28 individuals without HOA; of these, 12 were apparently healthy individuals, 7 had cyanosis secondary to chronic obstructive pulmonary disease, and 9 had lung cancer. ELISA was used to measure serum and plasma levels of VEGF. RESULTS: Plasma levels of VEGF were significantly higher in the patients with primary HOA (median 46.2; range 19.4-398.8 pg/ml) and in those with lung cancer-HOA (median 75.5; range 24.6-166.7), compared to healthy controls (median 7.4; range: 0-26.1), p < 0.05. Serum VEGF levels were higher in patients with lung cancer and HOA (median 411.4; range 164.2-959.5 pg/ml) compared with lung cancer patients without HOA (median 74.5; range 13.2-205.4), p < 0.001. CONCLUSIONS: Patients with primary HOA and those with HOA and lung cancer have increased circulating levels of VEGF. This cytokine may play a role in the pathogenesis of HOA.