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1.
Braz J Med Biol Res ; 51(8): e7138, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29846436

RESUMO

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.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Cofilina 1/análise , Neoplasias Pulmonares/química , Escarro/química , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Sensibilidade e Especificidade
2.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;51(8): e7138, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-951750

RESUMO

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.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Escarro/química , Carcinoma de Células Escamosas/química , Biomarcadores Tumorais/análise , Cofilina 1/análise , Neoplasias Pulmonares/química , Prognóstico , Ensaio de Imunoadsorção Enzimática , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Curva ROC , Sensibilidade e Especificidade , Proliferação de Células , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , Estadiamento de Neoplasias
3.
Braz J Med Biol Res ; 48(9): 852-62, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26200231

RESUMO

The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days) significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress.


Assuntos
Antioxidantes/farmacologia , Dano ao DNA/efeitos dos fármacos , Ericales/química , Neoplasias Pulmonares/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Carcinogênese , Carcinógenos , Ensaio Cometa , Genoma , Imuno-Histoquímica , Peroxidação de Lipídeos/efeitos dos fármacos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Uretana
4.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;48(6): 557-567, 06/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-748226

RESUMO

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.


Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma/química , Ácido Hialurônico/análise , Neoplasias Pulmonares/química , Escarro/química , Biópsia , Biomarcadores Tumorais/análise , Estudos de Casos e Controles , Carcinoma/patologia , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Pulmão/química , Pulmão/patologia , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Fumar/efeitos adversos , Células Estromais/química , Células Estromais/patologia
5.
Braz J Med Biol Res ; 48(6): 557-67, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25992645

RESUMO

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.


Assuntos
Carcinoma/química , Ácido Hialurônico/análise , Neoplasias Pulmonares/química , Escarro/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Carcinoma/patologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Pulmão/química , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Fumar/efeitos adversos , Estatísticas não Paramétricas , Células Estromais/química , Células Estromais/patologia
6.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;47(7): 567-575, 07/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-712970

RESUMO

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.


Assuntos
Animais , Masculino , Apoptose/fisiologia , Colágeno Tipo V/biossíntese , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar/patologia , Telomerase/metabolismo , Hidroxitolueno Butilado , Proliferação de Células , Colágeno Tipo I/análise , Colágeno Tipo II/análise , Colágeno Tipo V/análise , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Imunofluorescência , Fibroblastos/metabolismo , Fibroblastos/patologia , Hidroxiprolina/análise , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/ultraestrutura , Coloração e Rotulagem , Telomerase/isolamento & purificação
7.
Braz J Med Biol Res ; 47(7): 567-75, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24919172

RESUMO

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.


Assuntos
Apoptose/fisiologia , Colágeno Tipo V/biossíntese , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar/patologia , Telomerase/metabolismo , Animais , Hidroxitolueno Butilado , Proliferação de Células , Colágeno Tipo I/análise , Colágeno Tipo II/análise , Colágeno Tipo V/análise , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Imunofluorescência , Hidroxiprolina/análise , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/ultraestrutura , Coloração e Rotulagem , Telomerase/isolamento & purificação
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