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1.
Clin Exp Metastasis ; 33(4): 297-307, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26873137

RESUMEN

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can increase survival of colorectal cancer (CRC) patients with peritoneal metastases (PM). This treatment is associated with high morbidity and mortality rates. Therefore, improvement of patient selection is necessary. Assuming that the clinical phenotype is dictated by biological mechanisms, biomarkers could play a crucial role in this process. Since it is unknown whether and to what extent angiogenesis influences the course of disease in patients with PM, we investigated the expression of two angiogenesis-related markers and their relation to overall survival (OS) in CRC patients after CRS and HIPEC. Clinicopathological data and tissue samples were collected from 65 CRC patients with isolated metastases to the peritoneum that underwent CRS and HIPEC. Whole tissue specimens from PM were evaluated for versican (VCAN) expression, VEGF expression and microvessel density (MVD) by immunohistochemistry. The relation between these markers and OS was assessed using univariate and multivariate analysis. Associations between VEGF expression, VCAN expression, MVD and clinicopathological data were tested. High stromal VCAN expression was associated with high MVD (p = 0.001), better resection outcome (p = 0.003) and high T-stage (p = 0.027). High epithelial VCAN expression was associated with MVD (p = 0.007) and a more complete resection (p < 0.001). In multivariate analysis, simplified peritoneal cancer index (p = 0.001), VEGF expression levels (p = 0.012), age (p = 0.030), epithelial VCAN expression levels (p = 0.042) and lymph node status (p = 0.053) were associated with OS. Concluding, VCAN and VEGF were associated with survival in CRC patients with PM after CRS and HIPEC. Independent validation in a well-defined patient cohort is required to confirm the putative prognostic role of these candidate biomarkers.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Neoplasias Colorrectales/genética , Neoplasias Peritoneales/genética , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Versicanos/biosíntesis , Adulto , Anciano , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/cirugía , Procedimientos Quirúrgicos de Citorreducción , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Hipertermia Inducida , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/cirugía , Factor A de Crecimiento Endotelial Vascular/genética , Versicanos/genética
2.
Lasers Med Sci ; 30(7): 1931-9, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26188855

RESUMEN

Intense pulsed light (IPL) devices have been shown to be highly effective for the skin rejuvenation. In our study, we try to elucidate effects of IPL in fibroblast proliferation, in gene expression, and in extracellular matrix protein production. 1BR3G human skin fibroblasts were used to test the effects of an IPL device (MiniSilk FT, Deka®). Fibroblasts were divided into three groups: group 1 was irradiated with filter 800-1200 nm (frequency 10 Hz, 15 s, fluence 60.1 J/cm) twice; group 2 was irradiated with filter 550-1200 nm (double pulse 5 ms + 5 ms, delay 10 ms, fluence 13 J/cm2) twice; and group 3 was irradiated with filter 550-1200 nm (frequency 10 Hz, 15 s, fluence 60.1 J/cm2) twice. To determine changes in gene expression, messenger RNA (mRNA) levels for collagen types I and III and metalloproteinase 1 (MMP-1) were performed 48 h after irradiation. To determine changes in hyaluronic acid, versican, and decorin, mRNA and ELISA tests were performed after 48 h of treatment. In addition to this, a Picro-Sirius red staining for collagen was made. The study showed an increase of mRNA and hyaluronic acid, decorin, and versican production. With RT-PCR assays, an increase mRNA for collagen type I, type III, and MMP-1 was observed. Collagen and hyaluronic synthesis was increased in all groups with no differences among them, while decorin and versican synthesis was higher in those groups irradiated with 550-1200-nm filters with no dependence of type pulse or total energy dose. IPL applied in vitro cultured cells increases fibroblasts activity. Synthesis of extracellular proteins seems to be produced more specifically in determined wavelengths, which could demonstrate a biochemical mechanism light depending.


Asunto(s)
Colágeno Tipo III/metabolismo , Colágeno Tipo I/metabolismo , Rayos Láser , Metaloproteinasa 1 de la Matriz/metabolismo , Activación Transcripcional/efectos de la radiación , Línea Celular , Proliferación Celular , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Decorina/biosíntesis , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Expresión Génica , Humanos , Ácido Hialurónico/biosíntesis , Tratamiento de Luz Pulsada Intensa , Metaloproteinasa 1 de la Matriz/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Piel/citología , Versicanos/biosíntesis
3.
J Neurosci Res ; 87(13): 2937-50, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19437549

RESUMEN

Axonal injury is a major hallmark of traumatic brain injury (TBI), and it seems likely that therapies directed toward enhancing axon repair could potentially improve functional outcomes. One potential target is chondroitin sulfate proteoglycans (CSPGs), which are major axon growth inhibitory molecules that are generally, but not always, up-regulated after central nervous system injury. The current study was designed to determine temporal changes in cerebral cortical mRNA or protein expression levels of CSPGs and to determine their regional localization and cellular association by using immunohistochemistry in a controlled cortical impact model of TBI. The results showed significant increases in versican mRNA at 4 and 14 days after TBI but no change in neurocan, aggrecan, or phosphacan. Semiquantitative Western blot (WB) analysis of cortical CSPG protein expression revealed a significant ipsilateral decrease of all CSPGs at 1 day after TBI. Lower CSPG protein levels were sustained until at least 14 days, after which the levels began to normalize. Immunohistochemistry data confirm previous reports of regional increases in CSPG proteins after CNS injury, seen primarily within the developing glial scar after TBI, but also corroborate the WB data by revealing wide areas of pericontusional tissue that are deficient in both extracellular and perineuronal net-associated CSPGs. Given the evidence that CSPGs are largely inhibitory to axonal growth, we interpret these data to indicate a potential for regional spontaneous plasticity after TBI. If this were the case, the gradual normalization of CSPG proteins over time postinjury would suggest that this may be temporally as well as regionally limited.


Asunto(s)
Lesiones Encefálicas/metabolismo , Proteoglicanos Tipo Condroitín Sulfato/biosíntesis , Regulación de la Expresión Génica , Proteínas del Tejido Nervioso/biosíntesis , Animales , Lesiones Encefálicas/genética , Lesiones Encefálicas/patología , Proteoglicanos Tipo Condroitín Sulfato/genética , Cicatriz/etiología , Cicatriz/genética , Cicatriz/metabolismo , Cicatriz/patología , Gliosis/etiología , Gliosis/genética , Gliosis/metabolismo , Gliosis/patología , Masculino , Corteza Motora/lesiones , Corteza Motora/metabolismo , Proteínas del Tejido Nervioso/genética , Plasticidad Neuronal , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Corteza Somatosensorial/lesiones , Corteza Somatosensorial/metabolismo , Factores de Tiempo , Versicanos/biosíntesis , Versicanos/genética , Cicatrización de Heridas
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