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1.
Braz. j. med. biol. res ; 51(8): e7138, 2018. tab, graf
Article Dans Anglais | LILACS | ID: biblio-951750

Résumé

Cofilin-1 (CFL1), a small protein of 18 kDa, has been studied as a biomarker due to its involvement in tumor cell migration and invasion. Our aim was to evaluate CFL1 as an indicator of malignancy and aggressiveness in sputum samples. CFL1 was analyzed by ELISA immunoassay in the sputum of 73 lung cancer patients, 13 cancer-free patients, and 6 healthy volunteers. Statistical analyses included ANOVA, ROC curves, Spearman correlation, and logistic regression. Sputum CFL1 levels were increased in cancer patients compared to cancer-free patients and volunteers (P<0.05). High expression of sputum CFL1 was correlated to T4 stage (P=0.01) and N stage (P=0.03), tobacco history (P=0.01), and squamous cell carcinoma histologic type (P=0.04). The accuracy of sputum CFL1 in discriminating cancer patients from cancer-free patients and healthy volunteers were 0.78 and 0.69, respectively. CFL1 at a cut-off value of 415.25 pg/mL showed sensitivity/specificity of 0.80/0.70 in differentiating between healthy volunteers and cancer patients. Sputum CFL1 was also able to identify cancer-free patients from patients with lung cancer. The AUC was 0.70 and, at a cut-off point ≥662.63 pg/mL, we obtained 60% sensitivity and 54% specificity. Logistic regression analysis controlled for tobacco history, histologic types, and N stage showed that cancer cell-associated CFL1 was an independent predictor of death. Smoker patients with squamous cell carcinoma, lymph node metastasis and sputum CFL1>1.475 pg/mL showed augmented chance of death, suggesting lung cancer aggressiveness. CFL1 presented diagnostic value in detecting lung cancer and was associated to tumor aggressiveness.


Sujets)
Humains , Mâle , Femelle , Adulte , Adulte d'âge moyen , Sujet âgé , Expectoration/composition chimique , Carcinome épidermoïde/composition chimique , Marqueurs biologiques tumoraux/analyse , Cofiline-1/analyse , Tumeurs du poumon/composition chimique , Pronostic , Test ELISA , Carcinome épidermoïde/mortalité , Carcinome épidermoïde/anatomopathologie , Études cas-témoins , Courbe ROC , Sensibilité et spécificité , Prolifération cellulaire , Tumeurs du poumon/mortalité , Tumeurs du poumon/anatomopathologie , Invasion tumorale , Stadification tumorale
2.
Braz. j. med. biol. res ; 48(6): 557-567, 06/2015. tab, graf
Article Dans Anglais | LILACS | ID: lil-748226

Résumé

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.


Sujets)
Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Carcinomes/composition chimique , Acide hyaluronique/analyse , Tumeurs du poumon/composition chimique , Expectoration/composition chimique , Biopsie , Marqueurs biologiques tumoraux/analyse , Études cas-témoins , Carcinomes/anatomopathologie , Test ELISA , Immunohistochimie , Tumeurs du poumon/anatomopathologie , Poumon/composition chimique , Poumon/anatomopathologie , Stadification tumorale , Reproductibilité des résultats , Facteurs de risque , Sensibilité et spécificité , Statistique non paramétrique , Fumer/effets indésirables , Cellules stromales/composition chimique , Cellules stromales/anatomopathologie
3.
Braz. j. med. biol. res ; 47(7): 567-575, 07/2014. tab, graf
Article Dans Anglais | LILACS | ID: lil-712970

Résumé

Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.


Sujets)
Animaux , Mâle , Apoptose/physiologie , Collagène de type V/biosynthèse , Fibrose pulmonaire idiopathique/anatomopathologie , Fibrose pulmonaire/anatomopathologie , Telomerase/métabolisme , Butylhydrotoluène , Prolifération cellulaire , Collagène de type I/analyse , Collagène de type II/analyse , Collagène de type V/analyse , Modèles animaux de maladie humaine , Cellules épithéliales/métabolisme , Cellules épithéliales/anatomopathologie , Technique d'immunofluorescence , Fibroblastes/métabolisme , Fibroblastes/anatomopathologie , Hydroxyproline/analyse , Immunohistochimie , Méthode TUNEL , Souris de lignée BALB C , Microscopie électronique , Alvéoles pulmonaires/anatomopathologie , Alvéoles pulmonaires/ultrastructure , Coloration et marquage , Telomerase/isolement et purification
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