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1.
N Engl J Med ; 381(12): 1124-1135, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31150573

RESUMO

BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Adolescente , Adulto , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Análise de Sobrevida , Adulto Jovem
2.
Chin J Traumatol ; 22(2): 63-68, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30962130

RESUMO

PURPOSE: Vehicle-pedestrian conflicts are common at road intersections when traffic lights change. However, the impact of traffic light on transportation safety and efficiency remains poorly understood. METHODS: A two-stage study was used to survey the proportion of intersections with conflicting traffic lights and the related transportation efficiency and safety were evaluated as well. First, a cross-sectional study estimated the proportion of signalized intersections with conflicting left-turning vehicle-pedestrian traffic lights in Changsha city, China. Second, a natural experiment compared transportation efficiency and safety between intersections with and without conflicting left-turning vehicle-pedestrian traffic lights. Risky conflicts, where motor vehicles violated laws and failed to yield to pedestrians in crosswalk were used as a surrogate for transportation safety. The number of motor vehicles and pedestrians passing through the intersections per second and per meter were used to estimate transportation efficiency. Data were collected and analyzed in 2015 (from March to December). A search of online news from domestic media sources was also conducted to collect pedestrian injury data occurring at the intersections. RESULTS: About one-fourth (57/216) intersections had conflicting left-turning traffic lights (95% CI: 20.5%, 32.3%). Risky vehicle-pedestrian conflicts were more frequently observed at intersections with conflicting lights compared to those without (incidence rate ratio (IRR) = 3.13; pedestrians: IRR = 4.02), after adjusting for type of day (weekday vs. weekend), the time period of observation, and motor vehicles traffic flow. Intersections without conflicting vehicle-pedestrian traffic lights had similar transportation efficiency to those with conflicting lights after controlling for covariates (p > 0.05). The systematic review of news media reports yielded 10 left-turning vehicle-pedestrian crash events between 2011 and 2017, involving 11 moderate or severe pedestrian injuries and 3 fatal pedestrian injuries. CONCLUSION: Over one-fourth of road intersections in Changsha city, China have conflicting left-turning traffic lights. Conflicting traffic lights cannot improve transportation efficiency, but increase risky conflicts between vehicles and pedestrians.


Assuntos
Acidentes de Trânsito/prevenção & controle , Acidentes de Trânsito/estatística & dados numéricos , Veículos Automotores/estatística & dados numéricos , Pedestres/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , China/epidemiologia , Estudos Transversais , Humanos , Segurança , Fatores de Tempo
3.
Int J Cancer ; 145(1): 295-305, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30613964

RESUMO

To report long-term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III-IVB (except T3-4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m2 d1), cisplatin (60 mg/m2 d1), and fluorouracil (600 mg/m2 /d civ d1-5) every 3 weeks. Patients from both groups received intensity-modulated radiotherapy concurrently with three cycles of 100 mg/m2 cisplatin every 3 weeks. After a median follow-up of 71.5 months, the IC plus CCRT group showed significantly better 5-year failure-free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure-free survival (88% vs. 79.8%, p = 0.030), and locoregional failure-free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein-Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long-term follow-up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.


Assuntos
Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nomogramas , Prognóstico , Reprodutibilidade dos Testes , Adulto Jovem
5.
Eur J Cancer ; 75: 150-158, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28235726

RESUMO

AIM OF THE STUDY: Previous results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC). METHODS: Patients with stage III-IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m2 weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m2 and fluorouracil 800 mg/m2/d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival. RESULTS: Two hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64-1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3-4 toxicities (p = 0.14). CONCLUSION: Adjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities. REGISTRATION NUMBER: NCT00677118.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/terapia , Neoplasias Nasofaríngeas/terapia , Adolescente , Adulto , Idoso , Carcinoma/mortalidade , Quimiorradioterapia/métodos , Quimiorradioterapia/mortalidade , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/mortalidade , China/epidemiologia , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Resultado do Tratamento , Adulto Jovem
6.
Lancet Oncol ; 17(11): 1509-1520, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27686945

RESUMO

BACKGROUND: The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial. METHODS: We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III-IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18-59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m2 on day 1), intravenous cisplatin (60 mg/m2 on day 1), and continuous intravenous fluorouracil (600 mg/m2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT01245959. FINDINGS: Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38-49), 3-year failure-free survival was 80% (95% CI 75-85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66-78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48-0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 [42%] vs 17 [7%]), leucopenia (98 [41%] vs 41 [17%]), and stomatitis (98 [41%] vs 84 [35%]). INTERPRETATION: Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities. FUNDING: Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Quimioterapia de Indução , Neoplasias Nasofaríngeas/terapia , Adulto , Carcinoma , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Humanos , Quimioterapia de Indução/efeitos adversos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Taxoides/administração & dosagem
7.
Ying Yong Sheng Tai Xue Bao ; 27(5): 1359-1367, 2016 May.
Artigo em Chinês | MEDLINE | ID: mdl-29732795

RESUMO

We investigated the fire impacts on nutrients in litter and soil, and their C:N:P stoichio-metry in forests of Great Xing'an Mountains. The studied sites differed in their burning year (post-fire 4, 14, 40, 70 years and unburned within 120 years) and had different topographic locations (sloped land and flat land). The results showed that there were significant differences in stoichio-metry characteristics of C, N, P for both litter and soil with different burning years. No significant fluctuation was observed for the litter C content, while the contents of litter N and P increased with the increasing post-fire recovery years. In specific, we found the contents of litter N and P decreased at post-fire 4 and 14 years and nearly recovered to the control level at 40 years after fire. Additionally, C:N and C:P ratios of litter decreased, but N:P ratio of litter increased following post-fire recovery time. The contents of C, N, P and their ratios (C:N, C:P and N:P) in soil decreased with soil depth. Soil C content exhibited an increasing trend following post-fire recovery time and was significantly higher than the control at post-fire 70 years in sloped land, but no significant difference in the flat land. Significant interactive effects between fire history and slope were observed in soil P content and C:P ratio. Soil P content was higher than the control at post-fire 4 years in sloped land, but was higher than the control at post-fire 40 years in flat land. The C:P ratio recovered to the control level at post-fire 14 years in sloped land, and there was no significant diffe-rence in flat land. Redundancy analysis showed that slope effect played a more vital role than fire history effect in soil organic layer, while fire history effect was the most important factor for the varia-tion of soil nutrients in soil mineral layer. In our study, nutrients of litter and soil were lower than the control level at post-fire 4 and 14 years. The quality of litter and soil was improved with accele-rated plant growth and litter decomposition following post-fire recovery time and recovered to the pre-fire level at post-fire 40 years, reaching a steady status.


Assuntos
Fogo , Florestas , Solo/química , Carbono/análise , China , Nitrogênio/análise , Fósforo/análise
8.
Oral Oncol ; 50(8): 717-20, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24844985

RESUMO

OBJECTIVES: The primarily aim of this phase II study is to evaluate the response rate (RR) and disease control rate (DCR). The secondary aim of this study is to assess the progression-free survival and overall survival of recurrent or metastatic nasopharyngeal carcinoma (NPC) patients treated with lobaplatin in combination with docetaxel. MATERIALS AND METHODS: Patients with recurrent and metastatic NPC received docetaxel (75 mg/m(2) on day 1) and lobaplatin (30 mg/m(2) on day 2) every 3 weeks for two to six courses. RESULTS: From April 2011 to July 2013, 39 patients were enrolled. In total, 3 patients (7.7%) had complete response, 21 (53.8%) had partial response, 9 (23.1%) had stable disease and 4 (10.3%) had progressive disease. The overall RR was 61.5% (95% CI, 46.2-76.8%), and the DCR was 84.6% (95% CI, 73.3-95.9%). The median time to progression was 10 months (95% CI, 7.3-12.8 months) after the median follow-up duration of 10.3 months (1.5-28.9 months). The most common grade 3/4 toxicities included leucopaenia and neutropaenia (17.9%), anaemia (5.1%) and increased aminotransferase level (2.6%). Other toxicities were grade 1/2 and minimal. CONCLUSION: Lobaplatin in combination with docetaxel demonstrated clinical activity and an acceptable toxicity profile in recurrent and metastatic NPC patients. Lobaplatin may be effective for recurrent and metastatic NPC patients who previously received cisplatin-based chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Nasofaríngeas/tratamento farmacológico , Metástase Neoplásica , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclobutanos/administração & dosagem , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Compostos Organoplatínicos/administração & dosagem , Recidiva , Taxa de Sobrevida , Taxoides/administração & dosagem
9.
Pharmazie ; 69(5): 358-61, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24855827

RESUMO

Previously, we showed that treatment with celecoxib obviously inhibited proliferation of nasopharyngeal carcinoma (NPC) cell lines in a dose-dependent manner. However, the underlying molecular mechanisms of its anticancer effect on NPC have not been fully clarified. The present in vitro study was performed to investigate the mechanisms involved in the anticancer effect of celecoxib in NPC. NPC cell line HONE1 was treated with celecoxib at varying concentrations. The antiproliferation effect of celecoxib on the HONE1 cell line was assessed with methyl thiazolyl tetrazolium (MTT) assay. Western blot analysis of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3(Y705) (pSTAT3(Y705)), Survivin, Mcl-1, Bcl-2 and Cyclin D1 was carried out at various concentration of celecoxib for 48 h in HONE1 cell line. Western blot analysis of Protein Kinase B (AKT), phosphorylated AKT (pAKT) was performed at increasing doses of celecoxib for 48 h in HNE1, CNE1-LMP1 and HONE1 cells. The results showed that celecoxib inhibited proliferation of HONE1 cell line in a dose-dependent manner. Celecoxib inhibited the activation of STAT3 phosphorylation in HONE1 cells and the downstream genes of STAT3 (Survivin, Mcl-1, Bcl-2 and Cyclin D1) were downregulated after treatment with celecoxib. Furthermore, celecoxib could inhibit AKT phosphorylation in HNE1, CNE1-LMP1 and HONE1 cell lines. These data suggested that celecoxib was a promising agent for the chemoprevention and treatment of NPC.


Assuntos
Antineoplásicos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazóis/farmacologia , Fator de Transcrição STAT3/metabolismo , Sulfonamidas/farmacologia , Western Blotting , Celecoxib , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Corantes , Humanos , Fosforilação , Sais de Tetrazólio , Tiazóis
10.
Pharmazie ; 69(2): 132-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24640603

RESUMO

Celecoxib is a selective inhibitor of COX-2, whose connection with the development and progression of human tumors has been extensively studied. So far, however, its anti-metastatic effect is poorly understood in nasopharyngeal carcinoma. The current study aimed to observe the effect of celecoxib on invasion and migration of nasopharyngeal carcinoma cell lines and investigate the potential mechanism in vitro. Human nasopharyngeal carcinoma cell lines HNE1, HONE1, SUNE1-5-8F were exposed to different concentrations of celecoxib. MTT assay was used to study its anti-proliferation effect, transwell assay wound healing repair assay were performed to investigate the invasiveness and migration capability after treatment with celecoxib. The activity of MMP-2 and MMP-9 was measured by gelatin zymography. MTT assay showed that celecoxib inhibited HNE1, HONE1, and SUNE1-5-8F cells growth. Wound healing repair assay and transwell assay showed that cell metastatic ability was suppressed after treatment with celecoxib. Celecoxib had a significant inhibitory effect on the activity of MMP-2/9 in a dose-dependent manner in HNE1, HONE1 and SUNE1-5-8F cell lines. These data demonstrated that celecoxib-induced suppression of MMP-2 and MMP-9 activity might be involved in the inhibition of nasopharyngeal carcinoma cell lines invasion and migration.


Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Inibidores de Metaloproteinases de Matriz , Neoplasias Nasofaríngeas/tratamento farmacológico , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Carcinoma , Celecoxib , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Corantes , Relação Dose-Resposta a Droga , Humanos , Indicadores e Reagentes , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Sais de Tetrazólio , Tiazóis , Cicatrização/efeitos dos fármacos
11.
Int J Oncol ; 44(5): 1551-60, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24603891

RESUMO

Nasopharyngeal carcinoma (NPC) shows the highest invasive and metastatic features among head and neck cancers. Distant metastasis remains the predominant mode of treatment failure in NPC patients. The role of interleukin-6 (IL-6) in NPC progression is not fully understood. In this study, we explored whether IL-6 could promote the migration and invasion activity of NPC cell lines, as well as whether the effect of IL-6 on cell migration and invasion is mediated through regulating the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. Our results revealed that IL-6 and its receptors are broadly expressed in various NPC cell lines including HNE1, HONE1, CNE1, CNE1-LMP1 and 5-8F. Exogenous IL-6 enhanced cell proliferation slightly, but promoted cell migration and invasion significantly in both HNE1 and CNE1-LMP1 cell lines. In addition, an elevation in the expression of MMP-2 and MMP-9 could be induced by IL-6 stimulation. On the contrary, combining treatment with monoclonal anti-human IL-6R antibody (anti-IL-6R mAb) resulted in decreased proliferation, migration and invasion capabilities of NPC cells. Anti-IL-6R mAb also inhibited the expression of MMP-2 and MMP-9 in IL-6-stimulated HNE1 and CNE1-LMP1 cells. In summary, our data suggested that IL-6 mainly promotes the cell migration and invasion of NPC cells. The effect of IL-6 on cell migration and invasion may be mediated through regulation of the expression of MMP-2 and MMP-9. Thus, IL-6 or its related signaling pathways may be a promising target for preventing and inhibiting NPC metastasis.


Assuntos
Interleucina-6/genética , Interleucina-6/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Neoplasias Nasofaríngeas/metabolismo , Invasividade Neoplásica/patologia , Carcinoma , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/metabolismo , Transdução de Sinais
12.
Biomed Environ Sci ; 26(10): 853-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24215880

RESUMO

Pedestrian safety in China is an important but largely neglected issue, in part due to the substantial under-reporting within police data. In this study we aimed to examine changes in pedestrian fatality between 2006 and 2010 in China using non-police reported data. A multi-year study was conducted based on the mortality data during 2006-2010 from the Disease Surveillance Points (DSP) data in China. Between 2006 and 2010, the crude pedestrian mortality increased from 7.0 to 10.5 per 100 000 populations. Annual pedestrian mortality from DSP data was 13 times in 2006 and 55 times in 2010 mortality for pedestrians and passengers from police-reported data in the corresponding years. After controlling for sex, age, and urban/rural, the mortality increased by 44% from 2006 to 2010 (adjusted mortality rate ratio (MRR)=1.11, 95% CI 1.10-1.12). The problem of pedestrian deaths is much more serious in China than that officially reported by the police. Significant and urgent efforts are needed to save lives of pedestrian in China.


Assuntos
Acidentes de Trânsito , Polícia , China/epidemiologia , Humanos , Pedestres , População Rural , Ferimentos e Lesões
13.
Chin Med J (Engl) ; 126(12): 2242-7, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23786932

RESUMO

BACKGROUND: Angiogenesis is an essential step for tumor development and metastasis. The cell adhesion molecule avß3 integrin plays an important role in angiogenesis and is a specific marker of tumor angiogenesis. A novel avß3 integrin- targeted magnetic resonance (MR) imaging contrast agent utilizing Arg-Gly-Asp (RGD) and ultrasmall superparamagnetic iron oxide particles (USPIO) (referred to as RGD-USPIO) was designed and its uptake by endothelial cells was assessed both in vitro and in vivo to evaluate the angiogenic profile of lung cancer. METHODS: USPIO were coated with -NH3+ and conjugated with RGD peptides. Prussian blue staining was performed to evaluate the specific uptake of RGD-USPIO by human umbilical vein endothelial cells (HUVECs). Targeted uptake and subcellular localization of RGD-USPIO in HUVECs were confirmed by transmission electron microscopy (TEM). The ability of RGD-USPIO to noninvasively assess avß3 integrin positive vessels in lung adenocarcinoma A549 tumor xenografts was evaluated with a 4.7T MR scanner. Immunohistochemistry was used to detect avß3 integrin expression and vessel distribution in A549 tumor xenografts. RESULTS: HUVECs internalized RGD-USPIO significantly more than plain USPIO. The uptake of RGD-USPIO by HUVECs could be competitively inhibited by addition of free RGD. A significant decrease in T2 signal intensity (SI) was observed at the periphery of A549 tumor xenografts at 30 minutes (P < 0.05) and 2 hours (P < 0.01) after RGD-USPIO was injected via the tail vein. Angiogenic blood vessels were mainly distributed in the periphery of tumor xenografts with positive avß3 integrin expression. CONCLUSIONS: RGD-USPIO could specifically label avß3 integrin and be taken up by HUVECs. This molecular MR imaging contrast agent can specifically evaluate the angiogenic profile of lung cancer using a 4.7T MR scanner.


Assuntos
Dextranos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/uso terapêutico , Neovascularização Patológica/prevenção & controle , Oligopeptídeos/uso terapêutico , Animais , Células Cultivadas , Humanos , Integrina alfaVbeta3/análise , Neoplasias Pulmonares/irrigação sanguínea , Camundongos , Camundongos Endogâmicos BALB C
14.
Biomed Environ Sci ; 25(4): 407-12, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23026520

RESUMO

OBJECTIVE: To determine the prevalence of non-fatal injuries among children aged 5-14 years in China. METHODS: Data of 21 973 children aged 5-14 years were extracted from the Fourth National Health Service Survey of China carried out between June 15 and July 10, 2008. Injury-related indicators included: history of ever having had an injury, and injury frequency, cause, location and severity. RESULTS: The overall prevalence of non-fatal injuries among the children in the previous 12 months was 17.0 per 1000 subjects. The leading causes of non-fatal injuries were falls, animal bites, traffic accidents, falling objects and burns. The majority of children sustained only one injury. The main place of injury was at home in 40% and 54% of urban boys and girls, respectively, at school in 48% of rural boys, and at home and at school each in 33% of rural girls. Medical treatment for one day was the main option for 80% of urban boys and girls, 84% of rural boys, and 72% of rural girls. CONCLUSION: Nonfatal injuries among children aged 5-14 years are a serious public health concern in China.


Assuntos
Ferimentos e Lesões/epidemiologia , Acidentes/estatística & dados numéricos , Acidentes de Trânsito/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Coleta de Dados , Feminino , Humanos , Masculino , Prevalência , População Rural
15.
Oncol Rep ; 28(4): 1392-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22895543

RESUMO

The carboxyl terminus of heat shock cognate 70 interacting protein (CHIP) is an E3 ubiquitin ligase, which can promote ubiquitylation and degradation of many tumor-related proteins. However, the expression of CHIP in human gastric cancer has not been investigated. In this study, the mRNA and protein levels of CHIP expression in 53 cases of gastric cancer and matched normal tissues were determined by quantitative real-time PCR, western blotting and immunohistochemistry. We showed that CHIP was registered from basal to middle portions of normal gastric mucosa. CHIP expression was notably decreased or lost in human gastric cancer samples compared with the matched normal non-cancer samples. The correlations between CHIP downregulation and the clinicopathological characteristics were also evaluated. The expression of CHIP was significantly lower in the gastric cancer samples compared to the matched normal samples at both mRNA and protein levels (P<0.05 and P<0.05, respectively). More importantly, the downregulation of CHIP was correlated with TNM stage (P=0.048) and lymph node metastasis (P=0.010) at the mRNA levels. In addition, the downregulation of CHIP was correlated with lymph node metastasis (P=0.021) and tumor differentiation (P=0.009) at the protein levels. Taken together, at both mRNA and protein levels, the decreased expression of CHIP was correlated with lymph node metastasis. Furthermore, our study suggests that a negative correlation exists between CHIP expression and tumor malignancy in human gastric cancer.


Assuntos
Neoplasias Gástricas/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Mucosa Gástrica/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Valores de Referência , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Adulto Jovem
16.
Chin Med J (Engl) ; 125(13): 2322-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22882856

RESUMO

BACKGROUND: Magnetic resonance (MR) molecular imaging can detect abnormalities associated with disease at the level of cell and molecule. The epidermal growth factor receptor (EGFR) plays an important role in the development of lung cancer. This study aimed to explore new MR molecular imaging targeting of the EGFR on lung cancer cells. METHODS: We attached ultra-small superparamagnetic iron oxide (USPIO) particles to cetuximab (C225) anti-human IgG using the carbodiimide method. We made the molecular MR contrast agents C225-USPIO and IgG-USPIO, the latter as a control reagent, and determined concentrations according to the Fe content. Lung cancer A549 cells were cultured and immunocytochemistry (SP) was used to detect the expression of EGFR on cells. We detected the binding rate of C225-USPIO to A549 cells with immunofluorescence staining and flow cytometry. We cultured A549 cells with C225-USPIO at a Fe concentration of 50 µg/ml and assayed the binding of C225-USPIO after 1 hour with Prussian blue staining and transmission electron microscopy (TEM). We determined the effects on imaging of the contrast agent targeted to cells using a 4.7T MRI. We did scanning on the cells labeled with C225-USPIO, IgG-USPIO, and distilled water, respectively. The scanning sequences included axial T1WI, T2WI. RESULTS: Immunocytochemical detection of lung cancer A549 cells found them positive for EGFR expression. Immunofluorescence staining and flow cytometry after cultivation with different concentrations of C225-USPIO showed the binding rate higher than the control. Prussian blue staining and transmission electron microscopy revealed that in the C225-USPIO contrast agent group of cells the particle content of Fe in cytoplasmic vesicles or on surface was more than that in the control group. The 4.7T MR imaging (MRI) scan revealed the T2WI signal in the C225-USPIO group of cells decreased significantly more than in unlabeled cells, but there was no significant difference between the time gradients. CONCLUSIONS: We successfully constructed the molecular imaging agent C225-USPIO targeting the EGFR of A549 lung cancer cells. The imaging agent showed good targeting effect and specificity, and reduced MRI T2 value significantly, thus such molecular contrast agents could provide a new way to measure EGFR levels.


Assuntos
Anticorpos Monoclonais/química , Meios de Contraste/química , Receptores ErbB/metabolismo , Compostos Férricos/química , Neoplasias Pulmonares/metabolismo , Imagem por Ressonância Magnética/métodos , Anticorpos Monoclonais Humanizados , Linhagem Celular Tumoral , Cetuximab , Dextranos/química , Humanos , Imuno-Histoquímica , Nanopartículas de Magnetita/química , Microscopia Eletrônica de Transmissão
17.
Zhonghua Liu Xing Bing Xue Za Zhi ; 33(4): 382-5, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22781410

RESUMO

OBJECTIVE: To explore the risk factors on cases regarding work-related acute pesticide poisoning among farmers of Jiangsu province. METHODS: A population-based, 1:2 matched case-control study was carried out, with 121 patients as case-group paired by 242 persons with same gender, district and age less then difference of 3 years, as controls. Cases were the ones who had suffered from work-related acute pesticide poisoning. A unified questionnaire was used. Data base was established by EpiData 3.1, and SPSS 16.0 was used for both data single factor and multi-conditional logistics regression analysis. RESULTS: Results from the single factor logistic regression analysis showed that the related risk factors were: lack of safety guidance, lack of readable labels before praying pesticides, no regression during application, using hand to wipe sweat, using leaking knapsack, body contaminated during application and continuing to work when feeling ill after the contact of pesticides. Results from multi-conditional logistic regression analysis indicated that the lack of safety guidance (OR=2.25, 95%CI: 1.35-3.74), no readable labels before praying pesticides (OR=1.95, 95%CI: 1.19-3.18), wiping the sweat by hand during application (OR=1.97, 95%CI: 1.20-3.24) and using leaking knapsack during application (OR=1.82, 95%CI:1.10-3.01) were risk factors for the occurrence of work-related acute pesticide poisoning. CONCLUSION: The lack of safety guidance, no readable labels before praying pesticides, wiping the sweat by hand or using leaking knapsack during application were correlated to the occurrence of work-related acute pesticide poisoning.


Assuntos
Doenças Profissionais/epidemiologia , Praguicidas/envenenamento , Adulto , Idoso , Agricultura , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Rural
18.
Acta Pharmacol Sin ; 33(5): 682-90, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22504904

RESUMO

AIM: To investigate the mechanisms underlying the anticancer effect of celecoxib on nasopharyngeal carcinoma (NPC). METHODS: NPC cell lines, HNE1 and CNE1-LMP1, were treated with various concentrations of celecoxib for 48 h. The antiproliferative effect of celecoxib was assessed using MTT assay. Both cell cycle profiles and apoptosis were analyzed using flow cytometry. Western blot was used to measure the levels of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3(Y705) (pSTAT3(Y705)), COX-2, Survivin, Mcl-1, Bcl-2 and Cyclin D1. RESULTS: Celecoxib (10-75 µmol/L) inhibited the proliferation of the NPC cell lines in a dose-dependent manner. Celecoxib (25 and 50 µmol/L) induced apoptosis and cell-cycle arrest at the G(0)/G(1) checkpoint in the NPC cell lines, which was associated with significantly reduced STAT3 phosphorylation. The genes downstream of STAT3 (ie, Survivin, Mcl-1, Bcl-2 and Cyclin D1) were significantly down-regulated after exposure to celecoxib (25 and 50 µmol/L). CONCLUSION: The anticancer effects of celecoxib on NPC cell lines results from inducing apoptosis and cell cycle arrest, which may be partly mediated through the STAT3 pathway.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Nasofaríngeas/metabolismo , Pirazóis/farmacologia , Fator de Transcrição STAT3/metabolismo , Sulfonamidas/farmacologia , Western Blotting , Carcinoma , Celecoxib , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Citometria de Fluxo , Humanos , Interleucina-6/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Fosforilação , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
19.
Lancet Oncol ; 13(2): 163-71, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22154591

RESUMO

BACKGROUND: The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone. METHODS: We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3-4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m(2) cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0-2·27 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60-66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m(2) adjuvant cisplatin and 800 mg/m(2) per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT00677118. FINDINGS: 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3-61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81-90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78-88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49-1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of 205 patients treated with adjuvant chemotherapy). INTERPRETATION: Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials. FUNDING: Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010-178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010).


Assuntos
Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma , China , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Estadiamento de Neoplasias , Adulto Jovem
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 32(8): 773-6, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-22093465

RESUMO

OBJECTIVE: To determine the incidence of non-fatal injuries and related influencing factors among children under 5 years old in China. METHODS: Data involving 10 819 children under 5 years old was from the Fourth National Health Service Survey of China. Injury-related indicators include: history of ever having had an injury, its frequency, cause, location and severity of the injury. A two-level Poisson regression was used to examine the significance of related socio-economic variables. RESULTS: The overall incidence rate of nonfatal injuries among children under 5 years old was 16.0 per 1000 population in the prior 12 months. The first three leading causes of non-fatal injuries were falls, animal bite, fire/burn among children under 1 year old, with the rates as 3.9, 1.8 and 1.8 per 1000 population, respectively. For children aged 1 to 4 years old, the first three leading causes were animal bite, fall, fire/burn with rates as 6.5, 6.0 and 2.9 per 1000 population, respectively. 83.0% and 69.0% of last injuries occurred at home for the above said two age groups. No disability was found among children younger than 1 year old who suffered from a nonfatal injury while for the 1 - 4 age group, the disability accounted for 1.0% of injury-induced outcomes. After adjusting other variables, boys had 1.57 times the risk of injury compared with girls in the 1 - 4 age group (P < 0.05). The differences on the effects regarding ethnicity, per capita household income, and place were insignificant (P > 0.05). None of the socio-economic variables was found that significantly related to the non-fatal injury risk among children under 1 year old (P > 0.05). CONCLUSION: The incidence of nonfatal injuries among children under 5 years old was 16.0 per 1000 population in the prior 12 months. The three leading causes of injuries were animal bite, falls, fire/burn respectively. Home was the most common place that non-fatal injuries occurred. Boys had a higher risk of injury compared with girls among children aged 1 to 4 years old and the difference was significant.


Assuntos
Acidentes/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Fatores de Risco
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