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1.
Zhonghua Zhong Liu Za Zhi ; 42(3): 210-215, 2020 Mar 23.
Artigo em Chinês | MEDLINE | ID: mdl-32252199

RESUMO

Objective: To investigate the effects of osimertinib on proliferation, migration and invasion of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) overexpressing HCC827 cells and explore the potential mechanism of PLOD2 induced osimertinib resistance. Methods: We transfected HCC827 cells with LV-vector and LV-over/PLOD2. The expression of PLOD2 was detected by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. The effects of osimertinib on the proliferation of HCC827-vector and HCC827-PLOD2 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The effects of osimertinib on the migration and invasion of HCC827-vector and HCC827-PLOD2 cells were determined by Transwell assays. The expressions of E-cadherin and vimentin in cells were detected by immunofluorescence (IF). The expressions of epithelial-mesenchymal transition (EMT), FAK-PI3K/AKT and MAPK signal pathway related proteins were detected by western blotting. Results: The MTT assay showed that HCC827-PLOD2 cells were hyposensitive to osimertinib. The 50% inhibitory concentration (IC(50)) and resistance index of osimertinib for HCC827-PLOD2 cells was over 1 000 nmol/L and over 100, respectively. The result of wound healing assay showed that the migration distance of HCC827-PLOD2 was about (2.13±0.21) fold changes as that of HCC827-vector cells. The result of Transwell assay showed that the numbers of HCC827-PLOD2 passing through the matrix membrane were (212.78±10.43), significantly higher than (101.32±12.52) of HCC827-vector cells (P<0.01). The result of IF showed that compared with HCC827-vector cells, the expression of E-cadherin was down-regulated while vimentin was up-regulated in HCC827-PLOD2 cells. Osimertinb downregulated E-cadherin and upregulated vimentin expression in HCC827-vector cells but had limited effect in HCC827-PLOD2 cells. The result of western blotting showed that PLOD2 significantly increased vimentin expression level while decreased E-cadherin expression level. Osimertinib inhibited the expression of p-EGFR, but did not affect the expressions of PLOD2, p-FAK, p-AKT, p-ERK, vimentin and E-cadherin in HCC827-PLOD2 cells. Conclusion: PLOD2 confers resistance to osimertinib in HCC827 cells by regulating EMT, FAK-PI3K/AKT and MAPK signal pathways.


Assuntos
Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Transição Epitelial-Mesenquimal , Humanos , Fosfatidilinositol 3-Quinases , Inibidores de Proteínas Quinases
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(3): 215-218, 2020 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-32164091

RESUMO

Objective: To summarize and analyze the clinical and imaging characteristics of patients with 2019 novel coronavirus pneumonia in the early stage in Beijing. Methods: A retrospective analysis of clinical and imaging data of 9 patients with 2019 novel coronavirus infection diagnosed in one fever clinicic in Beijing from January 18, 2020 to February 3, 2020. Results: 5 male and 4 female was included in those 9 patients, whose median age was 36 years, and the age range from 15 to 49 years. 8 of these patients had no underlying disease and one suffered from diabetes. 7 patients had a history of travel to Wuhan City or Hubei Province, and one patient was a medical staff. Two family clustered was found. The incubation period was 1 to 6 days. The clinical manifestations were fever in 8 cases (8/9) , dry cough in 5 cases (5/9) , pharyngalgia in 4 cases (4/9) , fatigue in 4 cases (4/9) , body soreness in 4 cases (4/9) , and blocked or watery nose in 1 case (1/9) . Six patients (6/9) had abnormal cell peripheral blood, of which 3 (3/9) had an increased monocyte count, 2 (2/9) had a reduced lymphocyte, and 1 (1/9) had an increased leukocyte count, while the 3 patients had normal cell blood routines. The median of CRP was 16.3 mg/L, including 5 patients with slightly elevated (5/9) , 4 patients with normal values (4/9) . the results of procalcitonin test were negative in5 patients. Three patients were examined by chest X-ray examination, one of which was normal, one case showed infiltrates of right upper lung, and another showed in right lower lung. All patients underwent chest HRCT. And 7 cases (7/9) showed multiple ground glass exudation, including 5 cases (5/7) involved bilateral lungs, 2 cases (2/7) involved unilateral lung, 3 cases (3/7) with patchy consolidation, and 2 cases (2/9) showed no abnormality. Conclusions: The patents with 2019 novel coronavirus pneumonia in this study generally have an epidemiological history. The clinical manifestations are fever and cough. Peripheral white blood cell counts were most normal And PCT were all negative. Chest HRCT manifested as multiple ground-glass opacities with partly consolidation. Some patients had normal chest radiographs but HRCT showed pneumonia. Some patients had no pneumonia on chest HRCT.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pulmão , Pneumonia Viral/diagnóstico por imagem , Adolescente , Adulto , Pequim/epidemiologia , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Biomarcadores , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Tosse/etiologia , Saúde da Família , Fadiga/etiologia , Feminino , Febre/etiologia , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Pneumonia Viral/transmissão , Radiografia Torácica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Viagem , Adulto Jovem
3.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(0): E013, 2020 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-32061066

RESUMO

Objective: To summarize and analyze the clinical and imaging characteristics of patients with 2019 novel coronavirus pneumonia in the early stage in Beijing. Methods: A retrospective analysis of clinical and imaging data of 9 patients with 2019 novel coronavirus infection diagnosed in one fever clinicic in Beijing from January 18, 2020 to February 3, 2020. Results: 5 male and 4 female was included in those 9 patients, whose median age was 36 years, and the age range from 15 to 49 years. 8 of these patients had no underlying disease and one suffered from diabetes. 7 patients had a history of travel to Wuhan City or Hubei Province, and one patient was a medical staff. Two family clustered was found. The incubation period was 1 to 6 days. The clinical manifestations were fever in 8 cases (8/9) , dry cough in 5 cases (5/9) , pharyngalgia in 4 cases (4/9) , fatigue in 4 cases (4/9) , body soreness in 4 cases (4/9) , and blocked or watery nose in 1 case (1/9) . Six patients (6/9) had abnormal cell peripheral blood, of which 3 (3/9) had an increased monocyte count, 2 (2/9) had a reduced lymphocyte , and 1 (1/9) had an increased leukocyte count, while the 3 patients had normal cell blood routines. The median of CRP was 16.3 mg/L, including 5 patients with slightly elevated (5/9) , 4 patients with normal values (4/9) . the results of procalcitonin test were negative in5 patients. Three patients were examined by chest X-ray examination, one of which was normal, one case showed infiltrates of right upper lung, and another showed in right lower lung. All patients underwent chest HRCT. And 7 cases (7/9) showed multiple ground glass exudation, including 5 cases (5/7) involved bilateral lungs, 2 cases (2/7) involved unilateral lung, 3 cases (3/7) with patchy consolidation, and 2 cases (2/9) showed no abnormality. Conclusions: The patents with 2019 novel coronavirus pneumonia in this study generally have an epidemiological history. The clinical manifestations are fever and cough. Peripheral white blood cell counts were most normal And PCT were all negative. Chest HRCT manifested as multiple ground-glass opacities with partly consolidation. Some patients had normal chest radiographs but HRCT showed pneumonia. Some patients had no pneumonia on chest HRCT.

4.
Zhonghua Zhong Liu Za Zhi ; 41(6): 435-440, 2019 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-31216829

RESUMO

Objective: To investigate the relationship of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression and the clinical characteristics of osteosarcoma, and explore the potential mechanism of tumour metastasis promoted by PLOD2. Methods: The expression of PLOD2 in osteosarcoma tissues and paired adjacent tissues were detected by immunohistochemistry and qRT-PCR. Correlation of PLOD2 expression in osteosarcoma with the clinical pathologic features was analyzed by Chi square test and Kaplan-Meier analysis.Fibrillar collagen formation and collagen deposition in the tumor tissues were detected by picrosirius red staining. We transfected U-2OS cells with LV-vector, LV-over/PLOD2, sh-NC and sh-PLOD2. The expression of PLOD2 was detected by qRT-PCR. The impact of POLD2 on U-2OS cell invasion was determined by wound-healing assay and Transwell migration assay. The expressions of PLOD2/FAK/JAK2-STAT3 signal pathway related proteins were detected by western blotting. Results: The high expression level of PLOD2 in osteosarcoma tissues was 72.5%, significantly higher than 0% in paired adjacent noncancerous tissues (P<0.01), the expression of PLOD2 was positively correlated with lymph node metastasis, pulmonary metastasis and poor outcome (P<0.01). The same results were also observed in qRT-PCR assay. The median survival time of patients with high expression of PLOD2 protein was 13 months, significantly shorter than 32 months of patients with low expression of PLOD2 (P<0.05). The result of picrosirius red staining showed that the percentage of collagen fiber deposition in the osteosarcoma tissue with high level of PLOD2 was (74.43+ 9.63)%, significantly higher than (9.67±1.28)% in tissue with low expression of PLOD2 (P<0.001). The result of wound-healing and Transwell migration assay showed that over-expression of PLOD2 markedly promoted the invasion, however, knockdown of PLOD2 suppressed the invasion of U-2OS cells (both P<0.01). The result of western blotting showed that over-expression of PLOD2 significantly increased the expression levels of p-FAK, p-JAK2, p-STAT3, but knockdown PLOD2 decreased the levels of p-FAK, p-JAK2, p-STAT3 in U-2OS cells. Conclusions: Up-regulation of PLOD2 in osteosarcoma is correlated with lymphatic and distant metastasis. PLOD2 promotes invasion and metastasis of osteosarcoma might through FAK/JAK2-STAT3 signal pathway.


Assuntos
Neoplasias Ósseas/patologia , Osteossarcoma/patologia , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Regulação para Cima , Humanos , Invasividade Neoplásica , Metástase Neoplásica
5.
Zhonghua Zhong Liu Za Zhi ; 41(4): 257-262, 2019 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-31014050

RESUMO

Objective: To test the effect of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) and/or osimertinib on the proliferation and apoptosis of HCC827 cells, and explore the potential mechanism of MALAT1 induced resistance to osimertinib. Methods: We transfected HCC827 cells with LV-vector or LV-over/MALAT1. Stable transfected cells (HCC827/Vector, HCC827/MALAT1) were selected by adding puromycin. HCC827/MALAT1 cells were further transfected with the shRNA-negative control (NC) or shRNA-human epidermal growth factor receptor 3 (ERBB3) plasmid. The effects of overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib on the proliferation of HCC827 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. Cell apoptosis induced by MALAT1 overexpression, knockdown of ERBB3 and/or osimertinib treatment were analyzed by flow cytometry analysis. The expressions of EGFR and ERBB3 signal pathway related proteins in HCC827 cells treated with overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib treatment were detected by western blot. Results: The MTT assay showed that sensitivity to osimertinib of HCC827/MALAT1 cells were significantly repressed. The 50% inhibitive concentration (IC(50)) of osimertinib >4 000 nmol/L in HCC827/MALAT1 cells. However, knockdown of ERBB3 facilitated the anti-proliferation effect of osimertinib, and the IC(50) of osimertinib in shRNA-ERBB3 cells was (17.27±3.21) nmol/L. The results of flow cytometry analysis showed that the apoptotic rate of HCC827/MALAT1 cells induced by 10 nmol/L osimertinib was (8.38±0.92)%, significantly lower than (27.17±5.83)% of knockdown of ERBB3 (P<0.01). Western blotting showed that the expression of p-ERBB3, p-AKT and p-extracellular regulated protein kinases (ERK) in HCC827/MALAT1 cells was markedly up-regulated, while the expression of p-epithelial growth factor receptor (EGFR) was inhibited. The expressions of p-ERBB3, p-AKT and p-ERK were marginally affected by osimertinb. However, osimertinib downregulated the expressions of p-EGFR, p-ERBB3, p-AKT and p-ERK in ERBB3 deleted cells. Conclusions: MALAT1 confers resistance to osimertinb in HCC827 cells by activating of the ERBB3/PI3K/AKT and ERBB3/MAPK/ERK signaling pathways.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Piperazinas/uso terapêutico , RNA Longo não Codificante/metabolismo , Receptor ErbB-3/metabolismo , Acrilamidas , Compostos de Anilina , Biomarcadores Tumorais , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Receptor ErbB-3/genética
6.
Zhonghua Yi Xue Za Zhi ; 98(42): 3447-3452, 2018 Nov 13.
Artigo em Chinês | MEDLINE | ID: mdl-30440142

RESUMO

Objective: To investigate the effect of microRNA-221 (miR-221) overexpression on gefitinib resistance in PC-9 cells and study its underlying mechanisms. Methods: PC-9 cells were transfected with LV-NC and LV-miR-221 to establish cell stabilizing strains (PC-9/NC and PC-9/miR-221), then they were used to detect the relative expression of miR-221 and apoptotic protease activating factor-1 (APAF-1) mRNA by real-time fluorescence quantitative PCR (qRT-PCR). The effects of gefitinib (0-4 µmol/L) on the growth and proliferation of cell stabilizing strains were detected by CCK-8 Assay. After gefitinib treatment, cell apoptosis was detected by Flow Cytometry Assays. The expression of epidermal growth factor receptor (EGFR), phosphorylated epidermal growth factor receptor (p-EGFR), APAF-1 and cleaved cysteinyl aspartate specific proteinase-3 (Cleaved-caspase-3) were detected by Western blot. Dual-Luciferase Reporter Assay was used to evaluate the relationship between APAF-1 and miR-221. Results: The relative expression of miR-221 in PC-9/NC cells was significantly lower than that in PC-9/miR-221 cells[(1.00±0.082) vs (40.24±0.017)](P<0.01). The half maximal inhibitory concentration (IC(50)) in PC-9/NC cells was significantly lower than that in PC-9/miR-221 cells[(IC(50)=0.1 µmol/L) vs (IC(50)>4 µmol/L)](P<0.05). Apoptosis rate of PC-9/NC cell was significantly higher than PC-9/miR-221[(33.42±4.28)% vs (10.27±1.12)%](P<0.05); APAF-1 mRNA expression was significantly higher in PC-9/NC cells than PC-9/miR-221[(1.000+ 0.069) vs (0.701±0.072)](P<0.05), and the expression of APAF-1 protein in PC-9/NC cells was significantly higher than that of PC-9/miR-221 cells. The dual luciferase reporter gene results showed that miR-221a inhibited luciferase activity significantly stronger than transfected miRNA negative control group after co-transfection of luciferase plasmids pmir-REPORT-APAF-1-wt and miR-221a mimics (P<0.01). p-EGFR was down-regulated in both PC-9/NC and PC-9/miR-221 cells after treatment with gefitinib. APAF-1 and Cleaved-caspase-3 proteins were significantly down-regulated in PC-9/miR-221 cells compared with PC-9/NC cells, while APAF-1 and Cleaved-caspase-3 proteins were up-regulated in PC-9/NC cells treated with gefitinib compared with PC-9/miR-221 cells (P<0.05). Conclusion: miR-221 induces resistance to gefitinib in PC-9 cells by downregulating APAF-1 expression.


Assuntos
MicroRNAs/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Gefitinibe , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Mensageiro
7.
Zhonghua Wai Ke Za Zhi ; 56(6): 464-470, 2018 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-29886672

RESUMO

Objective: To investigate the prognostic effect of tumour-infiltrating immune cell, including CD8(+) T cell, regulatory T-cell (Treg) and myeloid-derived suppressor cells (MDSC) on pancreatic patients. Methods: This study retrospectively collected the data of 80 patients who were histologically diagnosed of pancreatic cancer and underwent classical R0 surgical resection at Tianjin Medical University Cancer Institute and Hospital from January 2010 to May 2012. All patients survival were followed up until the cut-off date of January 2015. Clinicopathological features including immunohistochemical staining of FOXP3, CD8 and CD33 were reviewed as indice for evaluating the prognosis of pancreatic patients.The prognostic effect of tumour-infiltrating immune cells were analysed by Kaplan-Meier and Log-rank test. Multiple-factor analysis was conducted with the Cox regression model. The correlation between tumour-infiltrating immune cells and clinicopathological features was analysed by χ(2) test. The C57BL/6 mouse model was used to evaluate the efficacy of Treg and MDSC depletion therapy in vivo. Student's t-test was applied to assess the difference of the tumour volume, Ki-67 positive rate and CD8(+) T-cell infiltration proportion between depletion group and control group. Results: Eventually, 80 patients were included and no patient was lost during the follow-up period. The median follow-up time was 33.2 months (7.4-59.9 months). Patients with high level of tumour-infiltrating CD8(+) T cells had longer overall survival (OS) time ((21.6±11.9)months vs. (13.6±7.4)months, χ(2)=4.647, P = 0.031) than those with low level of tumour-infiltrating CD8(+) T cells. Tumor infiltration FOXP3(+) cells were strongly associated with reduced OS((20.9±8.5)months vs.(13.4±8.8)months, χ(2)=10.528, P=0.001), reduced relapse free survival (RFS) ((15.2±9.0)months vs. (9.5±8.8)months, χ(2)=6.288, P=0.012) and larger tumor size(χ(2)=4.073, r=0.226, P=0.044). The high intratumoural MDSC group showed a significantly shorter OS((23.5±11.8)months vs. (13.8±7.6)months, χ(2)=5.724, P=0.017), RFS((17.9±11.3)months vs. (10.2±7.5)months, χ(2)=7.430, P=0.006) and more advanced N stage (χ(2)=4.714, r=0.243, P=0.030) than the low intratumoural MDSC group. Multivariate Cox analysis revealed that pTNM (P=0.008), tumour-infiltrating Treg density (P=0.009) and intratumoural MDSC density (P=0.034) were independent and negative prognostic factors for OS; pTNM(P=0.003) and tumour-infiltrating MDSC level(P=0.018) were independent and negative factors for RFS. The experiment in vivo revealed that Treg and MDSC depletion therapy significantly decreased tumour volume in the C57BL/6 mouse model of subcutaneous tumours((1 396.3±442.5)mm(3) vs. (3 356.9±533.5)mm(3), t=4.986, P=0.018). Tumour Ki-67 positive rate significantly decreased (23%±5% vs. 55%±10%, t=3.130, P=0.011) in Treg and MDSC depletion group, whereas, the proportion of tumour-infiltrating CD8(+) T cells significantly increased in depletion groups (3.25%±0.69% vs. 0.76%±0.25%, t=3.393, P=0.007). Conclusions: Tumour-infiltrating Treg, MDSC level and pTNM stage are independent prognostic factors for patients with pancreatic cancer. Treg and MDSC depletion therapy can significantly retard tumour growth and increase the level of tumour-infiltrating CD8(+) T-cells in the C57BL/6 mouse model of subcutaneous tumours.


Assuntos
Linfócitos T CD8-Positivos , Linfócitos do Interstício Tumoral , Neoplasias Pancreáticas , Animais , Fatores de Transcrição Forkhead , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/imunologia , Prognóstico , Estudos Retrospectivos
8.
Dis Esophagus ; 29(1): 54-61, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25059546

RESUMO

To explore the radiosensitivity of andrographolide on esophageal cancer cell line ECA109. The inhibition effects of andrographolide were measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. Clonogenic survival assay was used to evaluate the effects of andrographolide on the radiosensitivity of esophageal cancer cells. Immunofluorescence was employed to examine Bax expression. The changes in cell cycle distribution and apoptosis were assayed using flow cytometry. The expression of NF-κb/Cleaved-Caspase3/Bax/Bcl-2 was measured using Western blot analysis. DNA damage was detected via γ-H2AX foci counting. With a clear dose and time effects, andrographolide was found to inhibit the proliferation of esophageal cell line ECA109. The results of the clonogenic survival assay show that andrographolide could markedly enhance radiosensitivity (P < 0.05) with a sensitizing enhancement ratio of 1.28. Andrographolide caused a dose-dependent increase in Cleaved-Caspase3/Bax protein expression and a decrease in Bcl-2/NF-κb expression. Apoptosis in andrographolide-treated ECA-109 increased significantly compared with the apoptosis in the simple drug and radiation combined with drug groups (P < 0.001; P < 0.05). Moreover, compared with the independent radiation group, the andrographolide combined with radiation group increased the number of DNA double chain breaks. Andrographolide can increase the radiosensitivity of esophageal cell line ECA109. This result may be associated with the decrease in the NF-κb level and the induced apoptosis of esophageal cancer cells.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose , Diterpenos/farmacologia , Neoplasias Esofágicas , NF-kappa B/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/radioterapia , Humanos , Radiossensibilizantes/farmacologia , Estereoisomerismo , Sais de Tetrazólio/farmacologia
9.
Dis Esophagus ; 29(8): 1121-1127, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26663710

RESUMO

We conducted a retrospective analysis to assess the toxicity and long-term survival of esophageal squamous cell carcinoma patients treated with three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) versus conventional two-dimensional radiotherapy (2DRT). All data in the present study were based on four prospective clinical trials conducted at our institution from 1996 to 2004 and included 308 esophageal squamous cell carcinoma patients treated with 2DRT or 3DCRT/IMRT. Based on the inclusion and exclusion criteria, 254 patients were included in the analysis. Of these patients, 158 were treated with 2DRT, whereas 96 were treated with 3DCRT/IMRT. The rates of ≥Grade3 acute toxicity of the esophagus and lung were 11.5% versus 28.5% (P = 0.002) and 5.2% versus 10.8% (P = 0.127) in the 3DCRT/IMRT and 2DRT groups, respectively. The incidences of ≥Grade 3 late toxicity of the esophagus and lungs were 3.1% versus 10.7% (P = 0.028) and 3.1% versus 5.7% (P = 0.127) in the 3DCRT/IMRT and 2DRT groups, respectively. The 1-year, 3-year and 5-year estimated overall survival rates were 81%, 38% and 34% in the 3DCRT/IMRT group and 79%, 44% and 31% in the 2DRT group, respectively (P = 0.628). The 1-year, 3-year and 5-year local control rates were 88%, 71% and 66% in the 3DCRT/IMRT group and 84%, 66% and 60% in the 2DRT group, respectively (P = 0.412). Fewer incidences of acute and late toxicities were observed in esophageal squamous cell carcinoma patients treated with 3DCRT/IMRT compared with those treated with 2DRT. No significant survival benefit was observed with the use of 3DCRT/IMRT.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Lesões por Radiação/etiologia , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
10.
J Anim Sci ; 90(8): 2581-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22896732

RESUMO

The objective of this experiment was to investigate the influence of weaning stress and an antioxidant blend on gut health and free radical metabolism in postweaning pigs. A total of 96 pigs from 12 litters were randomly divided by litter to 3 groups with 4 litters each. The control group and the weaning group were fed the basal diet, and the antioxidant group was fed the basal diet supplemented with an antioxidant blend. The control group was suckling normally during the experimental period and the other 2 treatments were weaned at 21 d of age. Morphology in different parts of the intestines was used as a measure of intestinal barrier function. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the concentrations of malondialdehyde (MDA), NO, H(2)O(2), and O(2) were measured in serum. Activities of the digestive enzymes, including sucrase, maltase, amylase, lipase, and pepsin, were measured at 24 d of age for all treatments. Gene expressions of free radicals, digestive enzymes, or antioxidant enzymes were selected for quantitative reverse transcription-PCR analyses. Results showed that weaning resulted in reductions (P < 0.05) in the villus height and width, and activity of digestive enzymes. Activity of SOD decreased (P < 0.05) and the concentrations of MDA, NO, and H(2)O(2) increased (P < 0.05) after weaning. The expression results indicated that the genes related to the antioxidant enzymes and digestive enzymes were down regulated (P < 0.05) after weaning. Tumor protein 53, which regulates reactive oxygen-species generation, tended to increase (P < 0.10) in the weaning group. The concentration of PPARγ coactivator-1α (PGC-1α), which plays an important protective role against oxidative stress by regulating the expression of mitochondrial antioxidants, was reduced (P < 0.05) in weaning pigs and increased (P < 0.01) in antioxidant pigs compared with the control pigs. Results indicated that intestinal dysfunction occurred after weaning and there was an inhibition of the antioxidant system. The antioxidant blend has the potential to prevent free radical-induced damage and suppress oxidative stress by modulating the expressions of tumor protein 53 and PGC-1α genes.


Assuntos
Antioxidantes/farmacologia , Intestinos/efeitos dos fármacos , Suínos/metabolismo , Desmame , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Dieta/veterinária , Radicais Livres/metabolismo , Intestinos/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estresse Fisiológico
11.
J Hazard Mater ; 221-222: 28-34, 2012 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-22575176

RESUMO

This study investigated total mercury (THg) and methylmercury (MeHg) contamination in a major production center of compact fluorescent lamps (CFLs) located in Gaohong, Zhejiang Province, China. This was a result of the growing concern associated with the release of mercury into the environment from such components. The results of the study included the following mean concentrations for THg and MeHg of 157±11 (61-518)ng/gdw and 0.28±0.07 (0.07-0.67)ng/gdw in agricultural soil, respectively, and 18.6±6.5 (3.2-47.8)ng/gww and 0.11±0.03 (0.02-0.37)ng/gww in vegetable samples, respectively. A significant correlation was observed between THg in vegetables and corresponding soil samples (r=0.64, p<0.01). THg and MeHg in sediment samples had respective concentrations ranging from 28 to 1019ng/gdw and 0.11 to 3.15ng/gdw. Mud skipper bought from the local market contained the highest Hg (THg: 170±45ng/gww, MeHg: 143±37ng/gww) amongst all fish species (THg: 14-170; MeHg: 11-143ng/gww) of the study. The risk assessment indicated that fish consumption should not result in a MeHg EDI exceeding the RfD (0.1µg/kgbw/d) for both adults and children, when MeHg bioaccessibility is taken into account.


Assuntos
Contaminação de Alimentos , Iluminação , Mercúrio/toxicidade , Medição de Risco , Poluentes do Solo/toxicidade , Disponibilidade Biológica , China , Humanos , Mercúrio/farmacocinética , Controle de Qualidade , Poluentes do Solo/farmacocinética
12.
Clin Oncol (R Coll Radiol) ; 18(8): 621-7, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17051953

RESUMO

AIMS: To investigate the strength of association between anaemia and overall survival, locoregional control, and late radiation complications in patients with locally advanced oesophageal carcinoma undergoing radiotherapy with or without chemotherapy and hyperthermia. MATERIALS AND METHODS: Between March 1996 and December 2002, 303 patients with locally advanced squamous cell carcinoma of oesophagus enrolled in three consecutive prospective phase III trials conducted in our department were included in this study. These patients received one of the following four irradiation schedules: late course accelerated hyperfractionated (LCAF) radiotherapy alone, LCAF combined with concurrent chemotherapy, LCAF combined with hyperthermia, and continuous accelerated hyperfractionated (CAHF) radiotherapy according to each protocol. According to the haemoglobin levels measured before radiotherapy, patients were stratified to normal haemoglobin group (> or = 12.0 g/dl for men, or > or = 11.0 g/dl for women) or anaemic group (< 12.0 g/dl for men, or < 11.0 g/dl for women). Overall survival, locoregional control rate and late irradiation toxicity were estimated by Kaplan-Meier method. RESULTS: Of 303 eligible patients, 243 patients (80.2%) had normal haemoglobin level and 60 patients (19.8%) were anaemic. The 5-year overall survival was 39% in patients with normal haemoglobin level, whereas, 22%, with anaemia patients (P = 0.001). The 5-year locoregional control rate at 5 years was 68% in patients with normal haemoglobin, versus 62%, with anaemia patients (P = 0.050). The 5-year rate of radiation toxicity of grade 3 or greater was 29% in patients with normal haemoglobin level, but it was 8%, with anaemic patients (P = 0.033). From multivariate analyses, T stage, location of tumour and haemoglobin level were found to be independent predictors for survival. T stage, gender and haemoglobin level were independent predictors for locoregional control. It was also detected that age and haemoglobin level played as independent predictors for development of radiation toxicity. CONCLUSIONS: For patients with locally advanced oesophageal carcinoma undergone irradiation, anaemia associated a statistically significant reduction in survival and locoregional control rates, but also decreased radiation toxicity rates. Therefore, haemoglobin level should be considered as a stratification variable in prospective clinical trials.


Assuntos
Anemia/etiologia , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Hemoglobinas/análise , Radioterapia/efeitos adversos , Adulto , Idoso , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Terapia Combinada , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Dosagem Radioterapêutica
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