RESUMO
SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.
El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.
Assuntos
Humanos , Neoplasias Esofágicas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Proteínas de Membrana/metabolismo , Imuno-Histoquímica , Biomarcadores Tumorais , Western Blotting , MAP Quinases Reguladas por Sinal Extracelular , Proliferação de Células , Proteínas Proto-Oncogênicas c-aktRESUMO
PURPOSE: As a non-invasive treatment, stereotactic body radiation therapy (SBRT) has been an emerging and effective option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). The Cyber Knife has an SBRT system, which can realize real-time tracking of tumors during treatment. It can protect the surrounding normal liver tissue while the tumor gets the therapeutic dose. The purpose of this study was to evaluate the factors affecting the local control rate for patients after SBRT treatment, and to predict the factors affecting survival rates, then to report the 3-year actual survival rates after treatment and identify the influencing factors of 3-year survival rate. MATERIALS AND METHODS: We conducted a long-term follow-up of 43 patients with unresectable intrahepatic cholangiocarcinoma who underwent Cyber Knife in our hospital from January 2016 to December 2018. Regular medical check-ups were performed every 2-3 months after SBRT to evaluated the effect of treatment. RESULTS: The median follow-up time was 15 months (4-78 months), and the median progression-free survival (PFS) was 6 months (95% CI, 2.788-9.212) and the median overall survival (OS) was 12 months (95% CI, 3.434-20.566), respectively. Based on modified Response Evaluation and Criteria in Solid Tumor (mRECIST), response rate (RR) and disease control rate (DCR) of SBRT in unresectable ICC were 55.2% and 86%. The 1-, 2- and 3-years OS rate were 51.2%, 32.6% and 23.3%. Multivariate analysis based on competing risk survival analysis identified that patients with multiple nodules, large diameter, high level of CA199 and CEA, poor ECOG performance status had worse overall survival (p < 0.05). Patients who survived ≥3 years had significantly lower levels of CEA, CA199, smaller tumor diameters and lower number of lesions (p < 0.05). CONCLUSION: The SBRT might be a candidate option for patients who unable to perform surgery. The rate of 3-year survival after SBRT for unresectable ICC can be expected with 23.3%.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Radiocirurgia , Humanos , Radiocirurgia/efeitos adversos , Resultado do Tratamento , Colangiocarcinoma/radioterapia , Colangiocarcinoma/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/efeitos da radiação , Neoplasias dos Ductos Biliares/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the characteristics and treatment outcomes of patients with pediatric Langerhans cell histiocytosis (LCH) with thymic involvement. STUDY DESIGN: We retrospectively described the clinical, biological, and imaging characteristics of a series of 19 patients with pediatric LCH with thymic involvement in our center between September 2016 and December 2019. We further analyzed the treatment response and outcomes of patients treated with chemotherapy or targeted therapy. RESULTS: Thymic involvement was found in 4.4% of a 433-consecutive pediatric LCH cohort; all LCH-thymic involvement presented with multisystem disease. Patients with thymic involvement were typically younger, harboring more lung and thyroid involvement and less bone involvement than those without thymic involvement. Most patients with thymic involvement had alteration of immunocompetence with decreased numbers of T-lymphocyte subsets and immunoglobulin G levels. Overall, 47.1% of patients demonstrated a response after 6 weeks of induction therapy, and 92.3% of the patients who did not respond to the first-line treatment had resolution of thymus after the second-line and/or targeted therapy. The progression/relapse rate showed no difference between patients who shifted to second-line therapy and those to dabrafenib (33.3% vs 25%, P = 1.000). The survival for patients with thymic involvement did not differ from those without thymic involvement. More patients treated with second-line chemotherapy had severe adverse events than those given dabrafenib (88.9% vs 0, P < .001). CONCLUSIONS: Thymic involvement was observed rarely in LCH and had specific clinical characteristics. Chemotherapy could resolve most thymic lesions, and BRAF inhibitors might provide a promising treatment option with less toxicity for infants with BRAF-V600E mutation. TRIAL REGISTRATION: http://www.chictr.org.cn, identifier: ChiCTR2000030457 (BCH-LCH 2014 study); ChiCTR2000032844 (dabrafenib study).
Assuntos
Histiocitose de Células de Langerhans , Proteínas Proto-Oncogênicas B-raf , Criança , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/tratamento farmacológico , Humanos , Lactente , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: This study was conducted to investigate the risk factors for pulmonary abscess-related empyema by investigating the clinical characteristics and chest computed tomography imaging features of patients with pulmonary abscesses. METHODS: We retrospectively analyzed the chest computed tomography findings and clinical features of 101 cases of pulmonary abscess, including 25 cases with empyema (the experimental group) and 76 cases with no empyema (the control group). The potential risk factors for pulmonary abscess-related empyema were compared between the groups by using univariate and multivariate logistic regression analyses. RESULTS: The incidence of pulmonary abscess-related empyema was 24.8% (25/101). Univariate analysis showed that male gender, diabetes, pleuritic symptoms, white blood cells >10×109/L, albumin level <25 g/L, and positive sputum cultures were potential clinical-related risk factors and that an abscess >5 cm in diameter and transpulmonary fissure abscesses were potential computed tomography imaging-related risk factors for pulmonary abscess-related empyema. Multivariate logistic regression analysis showed that transpulmonary fissure abscesses (odds ratio=9.102, p=0.003), diabetes (odds ratio=9.066, p=0.003), an abscess >5 cm in diameter (odds ratio=8.998, p=0.002), and pleuritic symptoms (odds ratio=5.395, p=0.015) were independent risk factors for pulmonary abscess-related empyema. CONCLUSIONS: Transpulmonary fissure abscesses, diabetes, giant pulmonary abscesses, and pleuritic symptoms increased the risk of empyema among patients with pulmonary abscesses.
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Empiema Pleural/diagnóstico por imagem , Abscesso Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Complicações do Diabetes/complicações , Empiema Pleural/sangue , Empiema Pleural/complicações , Feminino , Humanos , Contagem de Leucócitos , Abscesso Pulmonar/sangue , Abscesso Pulmonar/complicações , Masculino , Pessoa de Meia-Idade , Doenças Pleurais/complicações , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica Humana/análise , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVES: This study was conducted to investigate the risk factors for pulmonary abscess-related empyema by investigating the clinical characteristics and chest computed tomography imaging features of patients with pulmonary abscesses. METHODS: We retrospectively analyzed the chest computed tomography findings and clinical features of 101 cases of pulmonary abscess, including 25 cases with empyema (the experimental group) and 76 cases with no empyema (the control group). The potential risk factors for pulmonary abscess-related empyema were compared between the groups by using univariate and multivariate logistic regression analyses. RESULTS: The incidence of pulmonary abscess-related empyema was 24.8% (25/101). Univariate analysis showed that male gender, diabetes, pleuritic symptoms, white blood cells >10×109/L, albumin level <25 g/L, and positive sputum cultures were potential clinical-related risk factors and that an abscess >5 cm in diameter and transpulmonary fissure abscesses were potential computed tomography imaging-related risk factors for pulmonary abscess-related empyema. Multivariate logistic regression analysis showed that transpulmonary fissure abscesses (odds ratio=9.102, p=0.003), diabetes (odds ratio=9.066, p=0.003), an abscess >5 cm in diameter (odds ratio=8.998, p=0.002), and pleuritic symptoms (odds ratio=5.395, p=0.015) were independent risk factors for pulmonary abscess-related empyema. CONCLUSIONS: Transpulmonary fissure abscesses, diabetes, giant pulmonary abscesses, and pleuritic symptoms increased the risk of empyema among patients with pulmonary abscesses.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Tomografia Computadorizada por Raios X/métodos , Empiema Pleural/diagnóstico por imagem , Abscesso Pulmonar/diagnóstico por imagem , Doenças Pleurais/complicações , Fatores Sexuais , Análise de Regressão , Fatores de Risco , Empiema Pleural/complicações , Empiema Pleural/sangue , Complicações do Diabetes/complicações , Albumina Sérica Humana/análise , Contagem de Leucócitos , Abscesso Pulmonar/complicações , Abscesso Pulmonar/sangueRESUMO
PURPOSE: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). METHODS: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. RESULTS: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). CONCLUSION: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.
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Lesão Pulmonar Aguda/fisiopatologia , Apoptose/fisiologia , Traumatismos por Explosões/fisiopatologia , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/patologia , Animais , Traumatismos por Explosões/sangue , Traumatismos por Explosões/patologia , Caspase 3/sangue , Modelos Animais de Doenças , Feminino , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Alvéolos Pulmonares/patologia , Coelhos , Distribuição Aleatória , Proteína X Associada a bcl-2/sangueRESUMO
Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P 0.01), while PaO2 was significantly reduced (P 0.01). The apoptosis index was significantly increased (P 0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P 0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.(AU)
Assuntos
Animais , Coelhos , Fator de Indução de Apoptose/análise , Lesão Pulmonar/veterinária , Traumatismos por Explosões/veterinária , Modelos Animais , Gasometria/veterináriaRESUMO
Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.
Assuntos
Animais , Masculino , Feminino , Coelhos , Traumatismos por Explosões/fisiopatologia , Apoptose/fisiologia , Lesão Pulmonar Aguda/fisiopatologia , Alvéolos Pulmonares/patologia , Traumatismos por Explosões/patologia , Traumatismos por Explosões/sangue , Distribuição Aleatória , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Modelos Animais de Doenças , Proteína X Associada a bcl-2/sangue , Caspase 3/sangue , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/sangueRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is correlated with obesity, but specific therapeutic interventions are lacking. Adiponectin is an adipokine with anti-inflammatory activity and is considered a hepatic protector. We aimed to investigate effects of a low-fat diet on the hepatic expression of adiponectin and its receptors in rats with NAFLD. MATERIALS AND METHODS: Sixteen male SD rats were fed a high-fat diet for 8 weeks (HFD1 group) or 16 weeks (HFD2 group) to induce NAFLD, and these rats were compared with rats on a normal diet for 8 weeks (NC1 group) or 16 weeks (NC2 group). Another group of 8 rats was fed an HFD for 8 weeks and then switched to a low-fat diet (DIET group) until the 16th week. The expression of hepatic adiponectin and its receptors was detected by western blotting, immunohistochemistry and RT-qPCR. RESULTS: The NAFLD activity score (NAS) in the HFD groups increased from 3.2 ± 0.45 (8th week) to 6.2 ± 0.84 (16th week) (P < 0.001), reflecting the progression in the NAFLD histology. In contrast to the HFD2 group, the low-fat diet ameliorated the steatosis, ballooning degeneration and inflammation. Dietary intervention augmented the expression of adiponectin and its receptors, which was down-regulated in the HFD2 group. CONCLUSIONS: The NAFLD rat model was successfully developed by feeding the animals a high-fat diet. Adiponectin may play a role in the pathogenesis of NAFLD, especially in the progression from steatosis to NASH. The low-fat diet alleviated the histological lesions associated with NAFLD by up-regulating the expression of adiponectin and its receptors.