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1.
J Occup Environ Med ; 65(3): 217-223, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36868862

RESUMO

BACKGROUND: The relationship between arsenic exposure and all-cause mortality and the joint effects of arsenic exposure and smoking have been poorly described in previous studies. METHODS: After 27 years of follow-up, a total of 1738 miners were included in the analysis. Different statistical methods were used to explore the relationship between arsenic exposure and smoking and the risk of all-cause mortality and various causes of death. RESULTS: A total of 694 deaths occurred during the 36,199.79 person-years of follow-up. Cancer was the leading cause of death, and arsenic-exposed workers had significantly higher mortality rates for all-cause, cancer, and cerebrovascular disease. All-cause, cancer, cerebrovascular disease, and respiratory disease increased with cumulative arsenic exposure. CONCLUSIONS: We demonstrated the negative effects of smoking and arsenic exposure on all-cause mortality. More effective actions should be taken to reduce arsenic exposure in miners.


Assuntos
Arsênio , Fumar Cigarros , Humanos , Causas de Morte , Seguimentos , Fumar
2.
Zootaxa ; 5141(6): 592-600, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-36095771

RESUMO

Three new species of the genus Hexarhopalus Fairmaire, 1891, all of the nominate subgenus, are described and figured from China: Hexarhopalus (Hexarhopalus) ferreri sp. nov. from Yunnan, H. (H.) tianbaoyanensis sp. nov. from Fujian, and H. (H.) yeziyangi sp. nov. from Jiangxi.


Assuntos
Besouros , Distribuição Animal , Animais , China
3.
Front Oncol ; 12: 817045, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35299746

RESUMO

Background: This special cohort reveals the effect of smoking cessation in occupational miners exposed to radon and arsenic. Methods: A total of 9,134 tin miners with at least 10 years of underground radon and arsenic exposure were enrolled beginning in 1992 and followed for up to 27 years. Detailed smoking information was collected at baseline, and information on smoking status was consecutively collected from 1992 to 1996. The Cox proportional hazards model was used to explore the relationship between time since smoking cessation and lung cancer. Results: A total of 1,324 lung cancer cases occurred in this cohort over 167,776 person-years of follow-up. Among populations exposed to radon and arsenic, miners after quitting smoking for 10 years or more had almost halved their lung cancer risk [adjusted hazard ratio (HR) = 0.55, 95% CI: 0.38-0.79], compared with current smokers. Among miners after quitting smoking for 5 years or more, lung cancer incidence approximately halved (HR = 0.52, 95% CI: 0.30-0.92) for squamous cell lung carcinoma, while it showed no significant decline for adenocarcinoma (HR = 0.79, 95% CI: 0.34-1.85). Conclusion: Smoking cessation for 10 years or more halved lung cancer incidence among miners exposed to radon and arsenic, and the benefit was more pronounced among squamous cell lung carcinoma.

4.
Ecotoxicol Environ Saf ; 232: 113233, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35093810

RESUMO

BACKGROUND: Occupational radon cohorts provide important information about exposure at residential level, which are difficult to observe prospectively. However, evidence about radon-related lung cancer risks from initial exposure in childhood or interaction between radon and smoking is still limited. METHODS: A total of 6017 tin miners with at least 10 years of underground radon exposure were enrolled beginning in 1992 and followed for up to 27 years. Lung cancer risks were estimated by modeling total and intensity of radon exposure. RESULTS: A total of 933 lung cancer cases occurred in this cohort over 89,092 person-years of follow up. Excess relative risk increased by 0.96% per cumulative working level month (WLM). A unique aspect of this population was the early age at first radon exposure for workers. Results showed that lung cancer risk from initial radon exposure in childhood (<13 years old) was greater than risk when first exposure occurred at later ages (13-17, 18-24, and ≥ 25 years old). Moreover, risk declined with years since last exposure and attained age, but increased with age at last exposure. Importantly, these patterns were stable after adjustment for tobacco use or arsenic exposure. For joint effects of radon and other agents, our results support sub-multiplicative as the most likely model for interaction between radon and tobacco use or arsenic exposure. CONCLUSION: This study highlights the possible importance of radon exposure in childhood in cancer etiology and suggests another potential strategy to mitigate the global lung cancer burden.


Assuntos
Neoplasias Pulmonares , Doenças Profissionais , Exposição Ocupacional , Radônio , Urânio , Adolescente , Adulto , Seguimentos , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/efeitos adversos , Radônio/toxicidade , Uso de Tabaco
5.
Environ Res ; 206: 112611, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-34968429

RESUMO

BACKGROUND: We explored the shape of the exposure-response relationship of arsenic-related lung cancer and the interaction between arsenic and tobacco use. METHODS: A total of 3278 tin miners with at least 10 years of arsenic exposure were enrolled since 1992 and followed up for 27 years. After excluding radon-exposed miners and former smokers, 1620 miners were included into the sub-cohort. Lung cancer risks were estimated by modeling total exposure and intensity of arsenic exposure. RESULTS: The cohort experienced 73,866 person-years and 414 lung cancer cases. Firstly, the ERR/mg/m3-year was 0.0033 (95% CI: 0.0014-0.0045) in arsenic concentration <3 mg/m3 and 0.0056 (95% CI: 0.0035-0.0073) in arsenic concentration ≥3 mg/m3. After adjusting for cumulative arsenic exposure, and the ERR/mg/m3 increased with increasing intensity (0.129 (95% CI: 0.039, 0.189)). Secondly, an unique aspect of this population was the early age at first arsenic exposure for workers. Results showed that lung cancer incidence risk from exposed in childhood (<13 years) was non-significantly greater than those in other age groups (13-17 and ≥ 18 years). Finally, the most likely joint effects of inhaled arsenic and tobacco use was sub-multiplicative. CONCLUSION: This study enlightened us that for fixed cumulative arsenic exposure, higher concentration over shorter duration might be more deleterious than lower concentration over longer duration. Substantial reductions in the lung cancer burden of smokers exposed to arsenic could be achieved by reductions in either exposure.


Assuntos
Arsênio , Neoplasias Pulmonares , Neoplasias Induzidas por Radiação , Doenças Profissionais , Exposição Ocupacional , Radônio , Adolescente , Arsênio/toxicidade , Seguimentos , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/epidemiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Estanho , Uso de Tabaco
6.
Front Public Health ; 10: 1012267, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36589990

RESUMO

Background: To explore the patterns of the exposure-response relationship between arsenic exposure and cardiovascular disease (CVD) mortality and investigate the effect of cigarette smoking on the association. Methods: Seven thousand seven hundred thirty-five tin miners with at least 10 years of arsenic exposure were enrolled since 1992 and followed up for 27 years. Each individual's air arsenic exposure at workplace was calculated by time weighted average arsenic concentration × exposure months. Detailed information on smoking was collected at baseline, and information on smoking status was collected for five consecutive years from 1992 to 1996. Hazard ratio (HR) and 95% confidence interval (CI) for the risk of CVD were estimated using Cox proportional hazards models. Results: A total of 1,046 CVD deaths occurred in this cohort over 142,287.7 person-years of follow up. We firstly reported that for equal cumulative exposure, participants exposed to higher concentrations over shorter duration had a higher risk of CVD mortality than those exposed to lower concentration over longer duration. The HR and 95% CI were 1.38 (95%CI: 1.03-1.85) in participants exposed to arsenic concentration (45.5-99.5 mg/m3), 1.29 (95%CI: 1.02-1.67) in 99.5-361.0 mg/m3. Further, participants with age at first exposure <18 years had a significantly higher risk of morality from CVD, cerebrovascular and heart diseases than those with ≥18 years. Finally, all synergy indices were greater than 1 (range, 1.11-2.39), indicating that the joint effect of arsenic exposure and cigarette smoking on CVD mortality was greater than the sum of their individual effect. Conclusions: Exposure to air arsenic at workplace is adversely associated with mortality from CVD, especially among smokers younger than 18 years and smokers.


Assuntos
Arsênio , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Arsênio/efeitos adversos , Seguimentos , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia
7.
Arch Med Sci ; 16(2): 253-259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190134

RESUMO

INTRODUCTION: The aim of the present study was to assess the efficacy of molecularly targeted agents (MTAs) in the treatment of elderly patients with metastatic oesophago-gastric cancer (mOGC). MATERIAL AND METHODS: We systematically searched electronic databases and abstracts presented at American Society of Clinical Oncology (ASCO) meetings up to January 31, 2017. Hazard ratios (HRs) were used to estimate overall survival (OS) and progression-free survival (PFS). Subgroup analysis and publication bias were also evaluated. All statistical analysis was conducted using Comprehensive Meta Analysis software (Version 2.0). RESULTS: A total of 2,149 elderly patients with mOGC from thirteen trials were included. Compared to non-MTA-containing regimens, OS was significantly improved in the MTA-containing regimens (HR = 0.86, 95% CI: 0.75-0.99, p = 0.037), but not for PFS (HR = 1.05, 95% CI: 0.85-1.30, p = 0.67). In addition, subgroup analysis indicated that MTA-containing regimens as second-line therapy in elderly mOGC patients significantly improved PFS (HR = 0.58; 95% CI: 0.39-0.85, p = 0.005) and OS (HR = 0.82, 95% CI: 0.70-0.96, p = 0.016), but did not significantly improve PFS (HR = 1.36; 95% CI: 1.06-1.76, p = 0.017) and OS (HR = 0.98, 95% CI: 0.77-1.27, p = 0.90) for MTA-containing regimens as first-line therapy in these patients. No publication bias was detected by Begg's and Egger's tests for OS and PFS. CONCLUSIONS: Our results indicate that the MTA-containing therapies significantly improve OS but not for PFS in elderly mOGC patients. Sub-group analysis shows that improved efficacy is only observed in the second-line setting and not in the first-line setting. Our findings support the use of angiogenesis as second-line treatment for elderly mOGC patients.

8.
Thorac Cancer ; 11(5): 1224-1232, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32196998

RESUMO

BACKGROUND: The performance of lung cancer screening with low-dose computed tomography (CT) (LDCT) in China is uncertain. This study aimed to evaluate the performance of LDCT lung cancer screening in the Chinese setting. METHODS: In 2014, a screening cohort of lung cancer with LDCT was established in Gejiu, Yunnan Province, a screening center of the Lung Cancer Screening Program in Rural China (LungSPRC). Participants received a baseline screening and four rounds of annual screening with LDCT in two local hospitals until June 2019. We analyzed the rates of participation, detection, early detection, and the clinical characteristics of lung cancer. RESULTS: A total of 2006 participants had complete baseline screening results with a compliance rate of 98.4%. Of these, 1411 were high-risk and 558 were nonhigh-risk participants. During this period, 40 lung cancer cases were confirmed, of these, 35 were screen-detected, four were post-screening and one was an interval case. The positive rate of baseline and annual screening was 9.7% and 9.0%, while the lung cancer detection rate was 0.4% and 0.6%, respectively. The proportion of early lung cancer increased from 37.5% in T0 to 75.0% in T4. Adenocarcinoma was the most common histological subtype. Lung cancer incidence according to the criteria of LungSPRC and National Lung Cancer Screening Trial (NLST) was 513.31 and 877.41 per 100 000 person-years, respectively. CONCLUSIONS: The program of lung cancer screening with LDCT showed a successful performance in Gejiu, Yunnan. However, further studies are warranted to refine a high-risk population who will benefit most from LDCT screening and reduce the high false positive results. KEY POINTS: This study reports the results of lung cancer screening with LDCT in Gejiu, Yunnan, a high-risk area of lung cancer, and it demonstrates that lung cancer screening with LDCT is effective in detecting early-stage lung cancer. Our program provides an opportunity to explore the performance of LDCT lung cancer screening in the Chinese context.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/epidemiologia , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/epidemiologia , China/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
9.
Sci Rep ; 9(1): 10639, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337846

RESUMO

Identification of rapid, inexpensive, and reliable prognostic factors can improve survival estimation and guide healthcare in patients with acute heart failure (AHF). In this study, we aimed to determine the prognostic value of the platelet-to-lymphocyte ratio (PLR) in patients with AHF. A total of 443 patients from two hospitals met the inclusion criteria from January 2010 to December 2017. Univariate and multivariate Cox analyses were performed to determine the association of PLR with survival. All-cause mortality was analysed using the Kaplan-Meier method. The 6-month survival rate for patients according to PLR quartiles (<110.63, 110.63-139.23, 139.23-177.17, and >177.17) were 90.09%, 76.79%, 50.07%, and 37.27%, respectively (p < 0.001). Univariate analysis identified high PLR (>110.63), old age (≥73 years), smoking habit, low estimated glomerular filtration rate (<57), and high platelet count (≥198 × 109/l) as poor prognostic factors for survival. In the multivariate analysis, after adjusting for confounding factors, the third (hazard ratio [HR] = 3.118, 95% confidence interval [CI] = 1.668-5.386, p < 0.001) and fourth (HR = 2.437, 95% CI = 1.302-3.653, p < 0.001) quartiles of PLR were identified as independent prognostic factors in patients with AHF. A higher PLR was associated with poor clinical outcomes in patients with AHF and might be a novel marker in AHF management.


Assuntos
Plaquetas , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Linfócitos , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Contagem de Linfócitos , Masculino , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
10.
Gene ; 693: 69-75, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30708027

RESUMO

The human SLC25A13 gene encodes the liver type aspartate/glutamate carrier isoform 2 (AGC2, commonly named as citrin), which plays a key role in the main NADH-shuttle of human hepatocyte. Biallelic SLC25A13 mutations result in Citrin deficiency (CD). In order to identify the important regulatory region of SLC25A13 gene and elucidate the way how potential promoter mutations affect the citrin expression, we performed promoter deletion analysis and established the reporter constructs of luciferase gene-carrying SLC25A13 promoter containing several mutations located in putative transcription factor-binding sites. The luciferase activities of all promoter constructs were measured using a Dual-Luciferase Reporter Assay System. Bioinformatic analysis showed that the promoter of SLC25A13 gene lacks TATA box and obviously typical initiator element, but contains a CCAAT box and two GC box. Promoter deletion analysis confirmed the region from -221 to -1 upstream ATG was essential for SLC25A13 to maintain the promoter activity. We utilized dual-luciferase reporter system as function analytical model to tentatively assess the effect of artificially constructed promoter mutations on citrin expression, and our analysis revealed that mutated putative CCAAT box and GC box could significantly affect the citrin expression. Our study confirmed the important SLC25A13 promoter regions that influenced citrin expression in HL7702 cells, and constructed a function analytical model. This work may be useful to further identify the pathogenic mutations leading to CD in the promoter region.


Assuntos
Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Sequência de Bases , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/fisiologia , Biologia Computacional , Humanos , Mutação , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/fisiologia , Regiões Promotoras Genéticas/genética
11.
Oncol Lett ; 15(5): 6655-6665, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29616128

RESUMO

Patients with non-small-cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) mutations generally react well to tyrosine kinase inhibitors (TKIs). However acquired resistance eventually occurs. Several mechanisms contribute to the resistance including T790M mutation, c-Met amplification and PIK3CA mutation. In recent years, cancer stem cells (CSCs) have been suggested to be involved in TKI resistance. MAP17 is aberrantly overexpressed in a number of malignancies. However, the expression pattern and function of MAP17 in CSCs are still unclear. The aim the present study was to illustrate the effect of CSC-like cells on the resistance to TKIs in EGFR mutant NSCLC cells and explore the possible role of MAP17 in CSCs. The EGFR mutant cell line PC9 was cultured under serum-deprived undifferentiated conditions. The CSC properties including expression of stem cell markers CD133, CD44, Oct-4 and ABCG2, ability of self-renewal, invasion, proliferation and tumorigenesis were examined. The expression of MAP17 was compared in sphere and parent cells. Sphere cells displayed stem cells phenotypes and were resistant to erlotinib. Sphere cells expressed higher levels of MAP17, and MAP17 was associated with self-renewal and TKI resistance. The function of MAP17 demonstrated to be partially dependent on Na-dependent glucose transporter 1. Collectively these findings suggest that MAP17 serves a role in TKI resistance through regulation of CSCs in lung cancer.

12.
Eur J Cardiothorac Surg ; 52(5): 958-962, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29088422

RESUMO

OBJECTIVES: The pattern of lymph node metastasis is a predominant element in tumour biology, which is closely related to optimal therapeutic modality. Controversy remains as to which histopathology type of oesophageal cancer-adenocarcinoma or squamous cell carcinoma (SCC)-is more likely to have lymph node metastasis. Therefore, this study aimed to apply propensity score-matched analysis to draw an objective conclusion for providing initial evidence of the potential need for different therapeutic strategies for these 2 cancer types. METHODS: A retrospective analysis of patients who underwent radical oesophagectomy with lymphadenectomy, but without preoperative treatment for pathologically and immunohistochemically diagnosed oesophageal adenocarcinoma or SCC, was conducted. Data for analysis included age, gender, body mass index, pathologic findings, procedures of oesophagectomy and rate of lymph node metastasis. Propensity score-matched analysis was conducted to eliminate the bias effects of confounding factors. RESULTS: A total of 1204 patients (including 118 with adenocarcinoma and 1086 with SCC) from January 2012 to June 2016 was included for analysis. In the analysis of unmatched patients, those with adenocarcinomas had significantly larger mean numbers of positive lymph nodes (3.8 and 1.5, respectively; P < 0.001) and higher rates of lymph node metastasis (71.2% and 49.0%, respectively; P < 0.001) than those with an SCC. However, other confounding factors such as surgical procedures, tumour location, pT stage and lymphovascular invasion also differed significantly between the adenocarcinoma and SCC cases. In the analysis of 96 matched patients, those confounding factors were well matched, and cases of adenocarcinoma still had a significantly larger mean number of positive lymph node (4.5 and 1.8, respectively; P = 0.003) and higher rate of lymph node metastasis (75.0% and 45.8%, respectively; P = 0.003) than did those with SCC. CONCLUSIONS: Cases of oesophageal adenocarcinoma had a higher risk of lymph node metastasis than did those with SCC in this series, which indicates that different therapeutic modalities should be applied for these 2 different malignant entities.


Assuntos
Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Metástase Linfática/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos
13.
ESMO Open ; 2(Suppl 1): e000174, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28848676

RESUMO

The diagnosis and treatment of lung cancer have evolved into the era of precision medicine. Liquid biopsy, a minimally invasive approach, has emerged as a promising practice in genetic profiling and monitoring of lung cancer. Translating liquid biopsy from bench to bedside has encountered various challenges, including technique selection, protocol standardisation, data analysis and cost management. Regarding these challenges, the 2016 Chinese Lung Cancer Summit expert panel organised a trilateral forum involving oncologists, clinicians, clinical researchers, and industrial expertise on the 13th Chinese Lung Cancer Summit to formally discuss these controversies. Six consensuses were reached to guide the use of liquid biopsy and perform precision medicine in both clinic and research.

14.
J Thorac Dis ; 9(4): 1065-1072, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28523161

RESUMO

BACKGROUND: Patients undergoing major thoracic surgery especially for cancers are at a high risk of perioperative thromboembolism. Current guidelines recommended either heparin sodium (unfractionated heparin) or low-molecular-weight heparin (LMWH) for those patients at high risk of deep vein thrombosis (DVT). However, the rational timing of starting heparin has not yet been well established, because DVT can be caused by not only surgery but also comorbidities as well as prolonged hospital stay, and thoracic surgeons always concerned about heparin-related increased risk of intra- or post-operative bleeding. Therefore, this study aimed to establish the safety profile of preoperative administration of heparin for thromboprophylaxis in Chinese patients intended for thoracoscopic major thoracic surgery. METHODS: From June to August 2016, patients intended for thoracoscopic lobectomy, esophagectomy, and thymectomy were randomly assigned into two groups: the case group (starting heparin sodium 5,000 U, bid preoperatively upon the admission into our department) and the control group (starting heparin sodium 5,000 U, bid postoperatively from postoperative day 1). The baseline data including demographic data and preoperative conditions were collected. The end points included operation time, intraoperative bleeding volume, postoperative chest tube drainage volume and duration as well as lab coagulation function data. RESULTS: A total of 58 qualified patients were randomized into case group (29 patients) and control group (29 patients), and after excluding 6 conversion patients, the case group and control group each had 26 patients for analysis. The baseline data of the two groups were comparable. Operation time (P=0.368), intraoperative bleeding volume (P=0.231), postoperative drainage days (P=0.466), and mean drainage volume per day (P=0.108) were not significantly increased in case group compared with those of control group. Moreover, there were no significant differences of perioperative coagulation function between these two groups. CONCLUSIONS: Preoperative administration of heparin for thromboprophylaxis in Chinese patients intended for thoracoscopic major thoracic surgery was safe and feasible. TRIAL REGISTRATION: NCT02940444 (https://register.clinicaltrials.gov/).

15.
Acta Pharmacol Sin ; 38(3): 371-381, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28248928

RESUMO

Long non-coding RNAs (lncRNAs) are associated with the occurrence, development and prognoses of non-small cell lung cancer (NSCLC). In the present study, we investigated the functional mechanisms of the lncRNA XIST in two human NSCLC cell lines, A549 and NCI-H1299. In all the 5 NSCLC cell lines (NL9980, NCI-H1299, NCI-H460, SPC-A-1 and A549) tested, the expression levels of XIST were significantly elevated, as compared with those in normal human bronchial epithelial cell line BEAS-2B. In A549 and NCI-H1299 cells, knockdown of XIST by siRNA significantly inhibited the cell proliferation, migration and invasion, and promoted cell apoptosis. Furthermore, XIST knockdown elevated the expression of E-cadherin, and suppressed the expression of Bcl-2. Moreover, knockdown of XIST significantly suppressed the tumor growth in NSCLC A549 xenograft mouse model. Bioinformatic analysis and luciferase reporter assays revealed that XIST was negatively regulated by miR-449a. We further identified reciprocal repression between XIST and miR-449a, which eventually influenced the expression of Bcl-2: XIST functioned as a miRNA sponge of miR-449a, which was a negative regulator of Bcl-2. These data show that expression of the lncRNA XIST is associated with an increased growth rate and metastatic potential in NSCLC A549 and NCI-H1299 cells partially through miR-449a, and suggest that XIST may be a potential prognostic factor and therapeutic target for patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Longo não Codificante/genética , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Invasividade Neoplásica , Transplante de Neoplasias
16.
Acta Pharmacol Sin ; 38(4): 539-550, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28112178

RESUMO

Isothiocyanates, such as allyl isothiocya¬nate (AITC), benzyl isothiocyanate (BITC), phenethyl isothio¬cyanate (PEITC) and sulforaphane (SFN), are natural compounds abundant in cruciferous vegetables, which have substantial chemopreventive activities against various human malignancies. However, the mechanisms underlying the inhibition of tumor cell growth by isothiocyanates are not fully understood. Since autophagy has dual functions in cancer, in the present study we investigated the effects of BITC on autophagy induction in human lung cancer cells in vitro and in vivo. BITC (1-100 µmol/L) dose-dependently inhibited the growth of 3 different human lung cancer cell lines A549 (adenocarcinoma), H661 (large cell carcinoma) and SK-MES-1 (squamous cell carcinoma) with IC50 values of 30.7±0.14, 15.9±0.22 and 23.4±0.11 µmol/L, respectively. BITC (10-40 µmol/L) induced autophagy in the lung cancer cells, evidenced by the formation of acidic vesicular organelles (AVOs), the accumulation of LC3-II, the punctate pattern of LC3, and the expression of Atg5. Pretreatment with the autophagy inhibitor 3-MA (5 mmol/L) significantly enhanced the BITC-caused growth inhibition in the lung cancer cells. Furthermore, BITC (20-40 µmol/L) activated ER stress, as shown by the increased cytosolic Ca2+ level and the phosphorylation of the ER stress marker proteins PERK and eIF2α in the lung cancer cells. Pretreatment with the ER stress inhibitor 4-PBA (5 mmol/L) attenuated the autophagy induction and potentiated the BITC-induced cell growth inhibition. In nude mice bearing A549 xenografts, administration of BITC (100 mg·kg-1·d-1, ip) for 8 weeks markedly suppressed the lung tumor growth, and significantly enhanced both autophagy and ER stress in the tumor tissues. Our results demonstrate that BITC inhibits human lung cancer cell growth in vitro and in vivo. In addition, BITC induces autophagy in the lung cancer cells, which protects the cancer cells against the inhibitory action of BITC; the autophagy induction is mediated by the ER stress response.


Assuntos
Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Isotiocianatos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Proteína 5 Relacionada à Autofagia/metabolismo , Linhagem Celular Tumoral , Feminino , Xenoenxertos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/metabolismo , Transplante de Neoplasias , Fenilbutiratos/farmacologia
18.
Thorac Cancer ; 6(6): 812-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26557925

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer-related death in China. Results from a randomized controlled trial using annual low-dose computed tomography (LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. METHODS: A China national lung cancer screening guideline was developed by lung cancer early detection and treatment expert group appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China. RESULTS: Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation. CONCLUSIONS: A lung cancer screening guideline is provided for the high-risk population in China.

19.
Thorac Cancer ; 6(1): 17-24, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26273330

RESUMO

Most tumor cells show different metabolic pathways than normal cells. Even under the conditions of sufficient oxygen, they produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, which is known as aerobic glycolysis or the Warburg effect. Lung cancer is a malignant tumor with one of the highest incidence and mortality rates in the world at present. However, the exact mechanisms underlying lung cancer development remain unclear. The three key enzymes of glycolysis are hexokinase, phosphofructokinase, and pyruvate kinase. Lactate dehydrogenase catalyzes the transfer of pyruvate to lactate. All four enzymes have been reported to be overexpressed in tumors, including lung cancer, and can be regulated by many oncoproteins to promote tumor proliferation, migration, and metastasis with dependence or independence of glycolysis. The discovery of aerobic glycolysis in the 1920s has provided new means and potential therapeutic targets for lung cancer.

20.
Tumori ; 100(5): e197-203, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25343558

RESUMO

AIMS AND BACKGROUND: Fast-track surgery has been shown to enhance postoperative recovery. The objective of the study was to determine the differences of fast-track surgery and conventional care for patients with gastroenteric neoplasms. METHODS AND STUDY DESIGN: We searched PubMed, EMBASE, and the Cochrane Library for related trials to compare hospital stay and rates of complications and readmission. RESULTS: Thirteen randomized controlled trials, with 1,962 patients, were included. Results showed the length of hospital stay was significantly reduced in the fast-track group. The complications rate was lowered in colorectal surgery. There were no significant differences in rate of readmissions. CONCLUSIONS: Current trials show that fast-track surgery may reduce the length of hospital stay and lower the rate of complications of gastroenteric surgery.


Assuntos
Neoplasias Colorretais/cirurgia , Neoplasias Gástricas/cirurgia , Humanos , Tempo de Internação , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
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