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1.
Cancer Biomark ; 19(1): 45-50, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28282799

RESUMO

BACKGROUND: Radiosensitivity by blocking the epidermal growth factor receptor and cyclooxygenase-2 pathways with erlotinib and celecoxib in A549 human lung cancer cell was investigated. METHODS: MTT assays were used to detect the antitumor effects of erlotinib and celecoxib in A549 cells. Colony formation assays were used to evaluate the antitumor effects. Flow cytometry analysis was used to assess the cell cycle and cell apoptosis, and western blotting analysis was performed to evaluate the expression of AKT and phosphorylated AKT. RESULTS: Either erlotinib or celecoxib inhibited the A549 cell proliferation in a dose-dependent manner. Combining Erlotinib or celecoxib with radiation can suppress the cell colony formation and the Dq, D0, SF2 of the combining erlotinib or celecoxib with radiation was lower than in the combinations either erlotinib or celecoxib with radiation (t= 6.62, P< 0.05). The SER of radiation with celecoxib or erlotinib and celecoxib and erlotinib were 1.299, 1.503 and 2.217, respectively. The Flow cytometry analysis results showed that either celecoxib or erlotinib could induce G0/G1 arrest, and reduction of S phase cell proportion, especially when combinations erlotinib-celecoxib with radiation. Either celecoxib or erlotinib could enhance radiation-induced apoptosis, especially significant when combinations erlotinib-celecoxib with radiation. Moreover, radiation can promote the expression of pAKT, and the pAKT was remarkably lowest in the combinations erlotinib-celecoxib with radiation group (t= 4.89, P< 0.05). CONCLUSIONS: Blocking both EGFR- and COX-2-related pathways could enhance the antitumor effect of radiation. The underlying mechanisms including the enhancement of apoptosis and radiation-induced G0/G1 arrest, possibly via inhibiting the PI3K/AKT signaling pathway.


Assuntos
Celecoxib/administração & dosagem , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Células A549 , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Terapia Combinada , Ciclo-Oxigenase 2/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/patologia , Proteína Oncogênica v-akt/antagonistas & inibidores , Inibidores de Fosfoinositídeo-3 Quinase , Tolerância a Radiação/efeitos dos fármacos
2.
Asian Pac J Cancer Prev ; 16(4): 1463-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25743816

RESUMO

BACKGROUND: To evaluate the safety and efficacy of combined chemoradiotherapy or radiotherapy alone in elderly patients with esophageal carcinoma to identify the best method of treatment. MATERIALS AND METHODS: One hundred and sixteen patients with esophageal carcinoma aged 70 and older who received definitive radiotherapy or chemoradiotherapy entered the study. Overall survival (OS), disease-free survival (DFS) and treatment- related toxicities were assessed. RESULTS: The median OS of the overall population was 17.9 months. For patients treated with cCRT, sCRT and radiotherapy alone, the median OS was 22.3 months, 18.0 months and 12.4 months respectively(P=0.044). Median OS for patients treated with radiotherapy dose ≥60Gy and <60Gy was 20.2 months and 10.9 months respectively (p=0.017). By univariate analysis, Chemoradiotherapy (include cCRT and sCRT) and radiotherapy dose ≥60Gy were found to achieve higher survival rates compared with radiotherapy alone and radiotherapy dose <60Gy (P=0.015, P=0.017). By multivariate analysis, chemoradiotherapy (HR=1.645, P=0.022) and radiotherapy dose ≥60Gy (HR=1.642, P=0.025) were identified as independent prognostic factors of OS. CONCLUSIONS: Definitive concurrent chemoradiotherapy could be considered as a feasible and effective treatment in esophageal carcinoma patients aged 70 and older. Radiotherapy dose 60Gy is an effective treatment option compared with standard dose radiotherapy, while higher doses are not beneficial to improve survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/mortalidade , Neoplasias Esofágicas/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida
3.
Int J Clin Exp Pathol ; 8(11): 14676-84, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26823791

RESUMO

Distant metastasis continues to be a fatal threat to quality of life in patients with small cell lung caner (SCLC). The purpose of this work is to analyze the expressions of chemokine receptor four (CXCR4), matrix metalloproteinase-9 (MMP-9), transforming growth factor-b1 (TGF-ß1), N-cadherin and vascular endothelial growth factor (VEGF) in small cell lung caner (SCLC), and to explore their correlations with the prognosis and metastasis. Sixty-five consecutive patients with stage I-III SCLC who received operation in our hospital from Jan 2003 to Oct 2009 were retrospectively analyzed. The expression of CXCR4 was found significantly correlated with bone metastasis (P = 0.004), and were marginally correlated with brain metastasis (P = 0.068) and lymph node metastasis (P = 0.085). The expression of MMP-9 was significantly associated with pathological staging (P = 0.048). Univariate analysis suggested surgical approach, clinical stage, lymph node metastasis were significantly associated with OS and PFS (P < 0.05), high expression of CXCR4 was significantly correlated with worse OS (P = 0.004) and PFS (P = 0.005). Multivariate analysis suggested surgical approach, TGF-ß1, CXCR4 and lymph node metastasis were independent prognostic factor for PFS. In conclusion, High expression of CXCR4, MMP-9, TGF-ß1 and VEGF were found in SCLC. High expression of MMP-9 was significantly associated with pathological staging, and high expression of CXCR4 was correlated with bone metastasis and also might correlate with brain metastasis. CXCR4 were independent prognostic factor for survival in SCLC and expanded samples should be further explored in the future.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Caderinas/análise , Caderinas/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/biossíntese , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Receptores CXCR4/análise , Receptores CXCR4/biossíntese , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Fator de Crescimento Transformador beta1/análise , Fator de Crescimento Transformador beta1/biossíntese , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/biossíntese
4.
Asian Pac J Cancer Prev ; 14(6): 3647-52, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23886160

RESUMO

PURPOSE: To evaluate the diagnostic value of 18F-FDG PET/CT for detection of bone metastasis in comparison with the efficacies of 18F-FDG PET/CT, CT, 18F-FDG PET and conventional planar bone scintigraphy in a series of cancer patients. METHODS: Five hundred and thirty patients who underwent both 18F-FDG PET/CT and bone scintigraphy within 1 month were retrospectively analyzed. The skeletal system was classified into 10 anatomic segments and interpreted blindly and separately. For each modality, the sensitivity, specificity, accuracy, PPV and NPV were calculated and the results were statistically analyzed. RESULTS: Bone metastases were confirmed in 117 patients with 459 positive segments. On patient-based analysis, the sensitivity, specificity, accuracy, PPV and NPV of 18F-FDG PET/CT were significantly higher than bone scintigraphy, CT and 18F-FDG PET (P<0.05). On segment-based analysis, the sensitivity of CT, bone scintigraphy, 18F-FDG PET and 18F-FDG PET/CT were 70.4%, 89.5%, 89.1% and 97.8%, respectively (P<0.05, compared with 18F-FDG PET/CT). The overall specificity and accuracy of the four modalities were 89.1%, 91.8%, 90.3%, 98.2% and 90.3%, 90.9%, 89.8%, 98.0%, respectively (P<0.05, compared with 18F-FDG PET/CT). The PPV and NPV were 89.8%, 87.6%, 85.6%, 97.2% and 85.6%, 93.2%, 92.8%, 98.6%, respectively. Three hundred and twelve lesions or segments were presented as lytic or sclerotic changes on CT images at the corresponding sites of increased 18F-FDG uptake. In lytic or mixed lesions, the sensitivity of 18F-FDG PET/CT and 18F-FDG PET were better than bone scintigraphy, while in osteoblastic lesions bone scintigraphy had a similar performance with 18F-FDG PET/CT but better than 18F-FDG PET alone. CONCLUSION: Our data allow the conclusion that 18F-FDG PET/CT is superior to planar bone scintigraphy, CT or 18F-FDG PET in detecting bone metastasis. 18F-FDG PET/CT may enhance our diagnosis of tumor bone metastasis and provide more information for cancer treatment.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Cintilografia , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Prognóstico , Estudos Retrospectivos
6.
Oncol Rep ; 21(1): 129-36, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19082453

RESUMO

Prostaglandin E2 has been implicated in cell growth and metastasis in many types of cancers. However, the effects of PGE2 and its mechanism on cell adhesion, migration, and invasion have not been clarified yet. In this study, we found PGE2 treatment significantly increased the cell adhesion, migration, and invasion in hepatocellular carcinoma (HCC) cells. In addition, the effects of PGE2 were found to be associated with focal adhesion kinase (FAK). PGE2 treatment increased the phosphorylation and synthesis of FAK in a dose-dependent manner. RNA interference targeting FAK suppressed PGE2-mediated cell adhesion and migration. Furthermore, the downstream proteins of FAK, paxillin and Erk2, were also activated by PGE2. PGE2 treatment increased the phosphorylation and synthesis of paxillin in a dose-dependent manner. PGE2 treatment also induced the phosphorylation of Erk2. PD98059, the specific inhibitor of MEK, suppressed PGE2-mediated cell adhesion and migration. However, it had no effect on PGE2-induced activation and synthesis of FAK. These results demonstrated that PGE2 greatly induced HCC cell adhesion, migration, and invasion by activating FAK/paxillin/Erk pathway.


Assuntos
Carcinoma Hepatocelular/metabolismo , Dinoprostona/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Neoplasias Hepáticas/metabolismo , Transdução de Sinais/fisiologia , Western Blotting , Carcinoma Hepatocelular/patologia , Adesão Celular/fisiologia , Movimento Celular/fisiologia , Células Cultivadas , Inibidores de Ciclo-Oxigenase 2/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/patologia , Invasividade Neoplásica/patologia , Paxilina/metabolismo , Fosforilação , Interferência de RNA
7.
Zhonghua Zhong Liu Za Zhi ; 30(4): 306-9, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-18788639

RESUMO

OBJECTIVE: To explore the diagnostic value of dual-time-point 18F-FDG PET-CT imaging in detecting hilar and mediastinal lymph node metastasis in non-small-cell lung cancer (NSCLC). METHODS: Forty-six patients with NSCLC underwent standard whole body single-time 18F-FDG PET-CT scans and a delayed imaging for the thorax alone before surgery, meanwhile, the standard uptake value (SUV) and retention index (RI) were calculated. RESULTS: A total number of 584 lymph nodes were excised in the 46 patients. Of these, 134 metastatic lymph nodes were pathologically confirmed in 31 patients. There were 189 lymph nodes detected and suspected to be metastatic by standard single-time 18 F-FDG PET-CT imaging, and 161 by dual-time-point imaging. Therefore, the sensitivity, specificity, diagnostic accuracy, positive predictive value and negative predictive value in the detection of hilar and mediastinal lymph node metastasis were 87.3%, 84.0%, 84.8%, 61.9% and 95.7% by standard single-time 18F-FDG PET-CT imaging, versus 94.8%, 92.2%, 92.8%, 78.9% and 98.1%, respectively, by dual-time-point imaging. There was a statistically significant difference in the detection of lymph node metastasis between the standard single-time imaging and dual-time-point 18F-FDG PET-CT imaging. CONCLUSION: Dual-time-point 18F-FDG PET-CT imaging is more sensitive, specific and accurate than standard single-time 18F-FDG PET-CT imaging in the detection of hilar and mediastinal lymph node metastasis, and may provide more information for diagnosis, staging and treatment of non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Masculino , Mediastino/patologia , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Fatores de Tempo
8.
Zhonghua Zhong Liu Za Zhi ; 30(9): 699-701, 2008 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-19173915

RESUMO

OBJECTIVE: To evaluate the value of (18)F-FDG PET-CT in detecting the primary tumor in patients with metastatic cancers of unknown primary origin. METHODS: Sixty-seven patients with metastatic cancers of unknown primary origin after extensive conventional diagnostic work-up were enrolled into this study. (18)F-FDG PET-CT scans were performed at approximately 60 minutes after the intravenous injection of 7.4 MBq (18)F-FDG/kg, then delayed imaging scans was done at approximately 180 minutes for detecting the primary focus. The standardized uptake value (SUV) >or= 2.5 on standard PET/CT imaging was considered as positive. Ten percent increase of retention index (RI) was also regarded as positive. The correlation between (18)F-FDG PET-CT results and histopathological and clinical findings were analyzed, and the SUV of detected primary focus and that of metastatic cancers were compared. RESULTS: Of the 67 patients, the primary tumors were identified in 39 (53.7%) by (18)F-FDG PET-CT, and 36 of them were confirmed by pathology or follow-up. Thirteen distant metastases and seventeen lymphatic metastases were newly discovered by whole body (18)F-FDG PET-CT imaging. The SUV of metastatic tumors was significantly lower than that of primary tumors (t = 3.470,P = 0.001) and closely correlated with that of the primary tumors (r = 0.738, P = 0.000). CONCLUSION: (18)F-FDG PET-CT is not only valuable in identifying the unknown primary tumor in patients with metastatic carcinoma, but can also be used to reveal the biological characteristics of the tumors by functional imaging.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Primárias Desconhecidas/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/secundário , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Tomografia Computadorizada por Raios X
9.
World J Gastroenterol ; 11(40): 6281-7, 2005 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-16419156

RESUMO

AIM: To investigate the cyclooxygenase-2 (COX-2) expression level in human HepG2, Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2 selective inhibitor celecoxib-induced cell growth inhibition and cell apoptosis. METHODS: Hepatoma cells were cultured and treated with celecoxib. Cell in situ hybridization (ISH) and immunocytochemistry were used to detect COX-2 mRNA and protein expression. Proliferating cell nuclear antigen and phosphorylated Akt were also detected by immunocytochemistry assay. Cell growth rates were assessed by 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium (MTT) bromide colorimetric assay. Celecoxib-induced cell apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and flow cytometry (FCM). The phosphorylated Akt and activated fragments of caspase-9, caspase-3 were examined by Western blotting analysis. RESULTS: Increased COX-2 mRNA and protein expression were detected in all three hepatoma cell lines. Celecoxib could significantly inhibit cell growth and the inhibitory effect was in a dose- and time-dependent manner evidenced by MTT assays and morphological changes. The apoptotic index measured by TUNEL increased correspondingly with the increased concentration of celecoxib and the reaction time. With 50 micromol/L celecoxib treatment for 24 h, the apoptotic index of HepG2, BEL-7402 and SMMC-7721 cells was 25.01+/-3.08%, 26.40+/-3.05%, and 30.60+/-2.89%, respectively. Western blotting analysis showed remarkable activation of caspase-9, caspase-3 and dephosphorylation of Akt (Thr(308)). Immunocytochemistry also showed the reduction of PCNA expression and phosphorylation Akt (Thr(308)) after treatment with celecoxib. CONCLUSION: COX-2 mRNA and protein overexpression in HepG2, Bel-7402 and SMMC-7721 cell lines correlate with the increased cell growth rate. Celecoxib can inhibit proliferation and induce apoptosis of hepatoma cell strains in a dose- and time-dependent manner.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Neoplasias Hepáticas , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Apoptose/fisiologia , Caspase 3 , Caspase 9 , Caspases/metabolismo , Celecoxib , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ativação Enzimática , Humanos , Hibridização In Situ , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo
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