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Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. Recent studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. In the present study, we find that the expression of lncRNA SPRY4-IT1 is significantly upregulated in ESCC cell lines as compared with human esophageal epithelial cell line HEEC. Overexpression of SPRY4-IT1 can increase in vitro motility of ESCC cells via induction of epithelial-mesenchymal transition (EMT), which is characterized by increasing the expression of vimentin (Vim) and fibronectin (FN) with a concomitant decrease of E-cadherin (E-Cad) and ZO-1, while silencing of SPRY4-IT1 significantly inhibits the in vitro motility of ESCC cells. Further, the knockdown of SPRY4-IT1 also significantly attenuates TFG-ß-induced EMT of ESCC cells. Further, lncRNA SPRY4-IT1 can directly increase the transcription, expression, and nuclear localization of Snail, one key transcription factor during the EMT processes of cancer cells, while siRNA-mediated specific knockdown of Snail can significantly attenuate SPRY4-IT1-induced EMT of ESCC cells. Our results suggest that lncRNA SPRY4-IT1 might be considered as a novel oncogene involved in ESCC progression.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Regulação da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Ativação Transcricional , Regulação para CimaRESUMO
OBJECTIVE: To evaluate the immunogenicity and safety of a boost dose of inactivated polio vaccine (IPV) among children aged 18 months who had been administered with primary doses of IPV. METHODS: Form 2011 to 2012, a total of 97 children were enrolled in the present study who were vaccinated with IPV at 2, 3, 4 months of age and boosted with the same vaccine at 18 months of age. Anti-poliovirus neutralizing antibody titers in serum were measured before and after booster vaccination, geometric mean titers (GMT) and seroprotection rate were calculated. Adverse events occurring within 30 days after booster vaccination were observed, including pain, redness/swelling and induration at the injection site, fever, vomit, abnormal crying, drowsiness, loss of appetite, irritability, and all other physical discomfort and related medications were also recorded. A descriptive analysis was performed for the safety assessment. RESULTS: Immunogenicity was assessed in 84 subjects. The pre-booster seropositivity rates of neutralizing antibody against poliovirus type 1, 2, 3 before booster were all 100% (84/84) and the corresponding GMT (95% CI) was 1: 148.5 (116.49-189.29) , 1: 237.68 (178.39-316.67) and 1: 231.87 (181.27-296.58) , respectively. The seropositivity rates of neutralizing antibody against the three types of poliovirus after booster were all 100% (84/84) and the corresponding GMT (95% CI) was 1: 1612.14 (1470.57-1767.34) , 1: 1854.92 (1715.83-2005.29) and 1: 1625.50 (1452.12-1819.58) , respectively. The pre-booster titer of neutralizing antibody against poliovirus type 1, 2, 3 mainly ranged 1: 128-1: 512, which accounted for 65% (55/84) , 55% (46/84) , 74% (62/84) in each type. After the booster immunization, titers of neutralizing antibody against type 1, 2, 3 were increased as subjects with titer ≥ 1: 1024 accounted for 94% (78/84) , 95% (80/84) , 92% (77/84) , respectively.Safety was evaluated in 96 subjects, of which 16 subjects reported adverse events with the rate of 17%. The observed local events were mainly tenderness 3% (3/96) , redness/swelling and induration were not reported. The systemic adverse events included loss of appetite (8%, 8/96) , irritability (8%, 8/96) , fever (7%, 7/96) , abnormal crying (6%, 6/96) , drowsiness (6%, 6/96) and vomit (1%, 1/96) . All reported adverse events were mild or moderate. All of the local events occurred in the day of vaccination and lasted for 1-2 days, while systemic events almost developed within 2 days after vaccination and last less than 3 days. CONCLUSION: IPV booster dose has good immunogenicity and safety profile, which provides effective protection against poliovirus.
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Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/imunologia , Vacina Antipólio de Vírus Inativado/uso terapêutico , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , China , Feminino , Humanos , Imunização Secundária/efeitos adversos , Lactente , Masculino , Vacina Antipólio de Vírus Inativado/efeitos adversosRESUMO
OBJECTIVE: To evaluate safety of different sequential immunization schedules of inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV) primary vaccination. METHODS: Infants of 2 months old (60-89 days) selected in Beijing, were assigned to four groups, 1 dose IPV plus 2 doses OPV (I-O-O), 2 doses IPV plus 1 dose OPV(I-I-O), 3 doses IPV (I-I-I), and 3 doses OPV (O-O-O), and were vaccinated at the age of 2, 3, 4 months, from 2009 to 2011. The frequencies of systemic as well as local injection site reactions after every dose were recorded and calculated. A total of 553 infants were enrolled in the study and 89 infants were quit, 1492 diseases were observed. RESULTS: The incidence of adverse events in I-O-O, I-I-O, I-I-I, O-O-O were 22.9% (94/410), 18.4% (60/327), 22.0% (78/354) and 17.7% (71/401) with no statistical differences (χ(2) = 4.84, P = 0.184). Dose 1 (22.7% (32/141)-35.3% (54/153) ) was more frequently than dose 2 and dose 3. No serious adverse events (SAE) were reported during the study. The incidence of systemic adverse reactions in I-O-O, I-I-O, I-I-I, O-O-O were 21.5% (88/410), 17.7% (58/327) , 20.1% (71/354) and 17.7% (71/401) with no statistical differences (χ(2) = 2.53, P = 0.472). Abnormal crying were the most frequency reactions (7.2% (29/401)-11.3% (37/327) ) in 4 groups. Rarely severe reactions were observed of abnormal crying, somnolence, irritability and mild or medium reactions occurred in other symptoms. Local adverse reactions such as injection site pain, scleroma and swelling were reported by 2.2% (5/229)-5.6% (22/393) ,0-0.9% (2/229) and 0-1.0% (4/393) in I-O-O,I-I-O and I-I-I, and most reactions were mild. CONCLUSION: Three IPV immunization and IPV/OPV sequential immunization as well as three OPV immunization demonstrated safe.
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Esquemas de Imunização , Vacina Antipólio de Vírus Inativado/efeitos adversos , Vacinas Atenuadas/efeitos adversos , Humanos , Lactente , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacinas Atenuadas/administração & dosagemRESUMO
BACKGROUND: The routine immunization program for children is a primary strategy and a core part of vaccination. Achieving and maintaining high level of vaccination coverage are important to reduce morbidity and mortality caused by vaccine-preventable diseases. In Beijing, annual coverage surveys have been conducted since 2005. It is necessary and possible to assess the level and trend of routine vaccination coverage of children in Beijing as well as the disruption of coronavirus disease 2019 (COVID-19) pandemic and provide the reference for the further improve the vaccination coverage. METHODS: The data of 61,521 children aged 1-3 years in the vaccination coverage surveys during 2005-2021 were analyzed by Beijing Center for Disease Control and Prevention. Descriptive epidemiological method was used to analyze the data and the difference of vaccination coverage within the time period. RESULTS: More than 99 % of participants had immunization cards and electronic immunization records. The concordance rate of both records were also over 99 %. During 2011-2019, the rates of on-time and in-time vaccination of each routine vaccine reached 96 % or more and increased significantly (all P values <0.05), compared with that of 2005-2010. All rates of the investigated vaccine, except for Bacillus Calmette-Guérin vaccine (BCG) and the first dose of hepatitis B vaccine (HepB), decreased in 2020-2021 significantly (all P values <0.05). For the causes of failing to vaccinate on time, delayed vaccination accounted for 47.82 %. The top two vaccines to be missed were the first dose of hepatitis A vaccine and the 4th dose of diphtheria-tetanus-acellular pertussis vaccine, accounting for 21.41 % and 20.79 %, respectively. The main reason for zero-dose/drop-out vaccination was "Guardians regarded the immunization service time as inappropriate", accounting for 72.27 %. CONCLUSION: The coverage level and service quality of routine immunization in Beijing were relatively high. However, as influenced by COVID-19 epidemics, both on-time and in-time vaccination rates decreased significantly, except for BCG and HepB. Under the background of COVID-19 pandemic, the keys to maintain high level of vaccination coverage include flexible immunization service time to ensure the guardians bringing their children for vaccination timely, and more attention from providers to the doses after children's first birthday.
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OBJECTIVE: To study the epidemiological impact of varicella vaccine vaccination on kindergartens and school children in Beijing. METHODS: According to "China Information System for Diseases Control and Prevention", the reported clinical diagnosis varicella cases were tracked in kindergartens, primary and secondary schools whose onset date were from 2008 to 2010. Epidemiological survey was conducted and epidemiological features were analyzed. RESULTS: A total of 21 474 varicella cases were investigated: 55.3% (11 883 cases) had been vaccinated by varicella vaccine. Of cases with definite immunization history, interval between vaccination date and onset date were from 30 days to 1 year accounted for 3.4% (286/8510), 1 to 3 years accounted for 18.2% (1551/8510), 3 to 5 years accounted for 28.6% (2431/8510), 5 to 10 years accounted for 34.3% (2916/8510) (left-closed right-open interval); The peak age of onset was 4 years old in cases without immunization history, which was 6 years old in cases with immunization history; The proportion of cases with immunization history (≥ 30 days) had increased from 42.4% (2862/6754) in 2008 to 56.3% (4327/7679) in 2010. The cases with no fever had a higher proportion (54.9%, 6413/11 679) of immunization history (≥ 30 days) than cases with fever (47.7%, 4533/9500) (P < 0.01); The cases with rashes less than 50 had a higher proportion (57.4%, 8045/14 020) of immunization history (≥ 30 days) than cases with rashes more than 50 (40.2%, 2902/7216) (P < 0.01). CONCLUSION: Varicella vaccine delays the peak age of onset, alleviates the symptoms. The current immunization strategy can not block varicella spread in kindergartens, primary and secondary schools.
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Vacina contra Varicela , Varicela/epidemiologia , Varicela/prevenção & controle , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Masculino , Instituições Acadêmicas , Escolas MaternaisRESUMO
OBJECTIVE: To evaluate immunogenicity after primary vaccination by different sequential program of inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV). METHODS: Children of 2 months old (60-89 days) selected in Beijing were assigned to 4 groups, 1 dose IPV plus 2 doses OPV (I-O-O, 122 children), 2 doses IPV plus 1 dose OPV(I-I-O, 103 children), 3 doses IPV (I-I-I, 114 children), and 3 doses OPV (O-O-O, 106 children), and were vaccinated at the age of 2, 3, 4 months. Polio neutralizing antibody titers against poliovirus types 1, 2, and 3 were tested and protective rates were calculated before the 1st dose, after the last dose, and after the 1st and 2nd dose of IPV. RESULTS: After the primary immunization, geometric mean titers (GMT) of polio neutralizing antibody titers against poliovirus types 1, 2, and 3 were 788.32, 738.42 and 631.17 in O-O-O group, 212.02, 262.30 and 537.52 in I-I-I group, 940.35, 929.72 and 940.35 in I-O-O group and 901.09, 1102.68 and 1110.12 in I-I-O group (F values were 47.71, 53.84, and 9.81 respectively, all P values<0.01). The protective rate of three types among each group was 98.1% (104/106)-100.0% and the difference was not statistically significant (P>0.05). After the 1(st) dose of IPV, the GMT were 18.88, 37.77, 24.64 and the protective rate was 82.6% (122/138)-96.4% (133/138); after the 2nd dose of IPV, GMT were 177.03, 168.25, 321.86 and the protective rate was 99.1% (108/109)-100.0% (109/109) in antibody types 1, 2 and 3, respectively. CONCLUSION: GMT of polio neutralizing antibody titers against poliovirus is higher after vaccination by sequential program of IPV and OPV than that by IPV or OPV 3-doses program. High level of protective rate after 2 doses of IPV in I-I-O group may lead to better protection from vaccine associated paralytic poliomyelitis (VAPP). Sequential program of IPV and OPV can be used to maintain high level of herd immunity and to prevent VAPP, and the I-I-O sequential program should be the first choice.
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Esquemas de Imunização , Vacina Antipólio de Vírus Inativado/imunologia , Vacina Antipólio Oral/imunologia , Vacinas Atenuadas/imunologia , Humanos , Lactente , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagemRESUMO
OBJECTIVE: To evaluate the safety of 2009 influenza A (H1N1) vaccine based on mass immunization initiative in Beijing. METHOD: There were 2 113 280 people were vaccinated during September to December 2009. The information of adverse events following immunization (AEFI) was collected through surveillance system, and descriptive methodology was used for data analysis. RESULTS: A Total of 612 AEFI cases were reported, among which there were 321 vaccine reaction cases following immunization, 203 coincidental illness cases, 82 psychogenic reaction cases, and 6 pending cases. The rates of rare reactions and common reactions associated with vaccination were respectively 5.54/100 000 (117/2 113 280) and 9.65/100 000 (204/2 113 280). The rate of serious rare reaction was 0.19/100 000 (4/2 113 280). The rates of vaccine reactions in urban, suburb and county were 16.87/100 000 (36/213 519), 17.81/100 000 (187/1 049 817) and 11.53/100 000 (98/849 944), respectively. The rates of rare reaction and common reaction in different age groups were between 3.65/100 000 (6/164 604) to 8.99/100 000 (27/300 176), and between 0.61/100 000 (1/164 604) to 22.06/100 000 (85/385 275). The 117 rear vaccine reaction cases were mainly allergic reaction (107 cases), and the 204 common vaccine reaction cases were mainly fever (176 cases). There were 91.90% (295/321) vaccine reactions occurred within 24 hours of administration, and all cases had improved consequence. CONCLUSION: The mostly symptoms of AEFI cases during the period of 2009 influenza A (H1N1) vaccinoprophylaxis were anaphylaxis and fever. The types of adverse reactions and the level of serious events are consistent with the anticipation. There were no rear or new events occurred.
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Vacinas contra Influenza/efeitos adversos , Influenza Humana/prevenção & controle , Vacinação em Massa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Febre/induzido quimicamente , Humanos , Hipersensibilidade/epidemiologia , Imunização , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , Adulto JovemRESUMO
OBJECTIVE: To explore the herd immunity against influenza A (H1N1) in pre-vaccinated residents aged over 5 years, and therefore to provide data for vaccination policies in high risk populations. METHODS: From October to December 2009, Beijing CDC conducted a serum survey of the novel influenza A (H1N1) in the local residents, stratified in 10 age groups between 5 years to over 60 years, without H1N1 vaccination history and disease history. Hemagglutination inhibition (HI) assays were performed at Beijing CDC. Statistical significance was determined with geometric mean titer (GMT). RESULTS: 3499 serum samples were tested for HI antibody. The average level of HI antibody was 1:8.03, and 11.06% (387/3499) were sero-positive (HI antibody level ≥ 1:40). In the group aged from 5 to 19 years, the level of HI antibody and the sero-positive rate were higher (HI antibody > 1:8.9, sero-positive rate > 12%). CONCLUSIONS: The antibody levels in different groups were affected by age specific morbidity, and the higher antibody level of the school-age group was correlated with higher disease intensity in this population. The data showed that the herd immunity in Beijing was under the optimal level, but influenza A (H1N1) would probably become prevalent in the short coming future.
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Anticorpos Antivirais/sangue , Imunidade Coletiva , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Adolescente , Adulto , Idoso , Anticorpos Antivirais/imunologia , Criança , Pré-Escolar , China , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: To explore the risk factors and prevention methods of cervical mechanical anastomotic fistula and stenosis after the radical resection of esophageal cancer. METHODS: From March 2018 to November 2018, 128 patients undergoing mechanical anastomosis of esophageal cancer were selected from the Department of Thoracic Surgery of The First Affiliated Hospital of Zhengzhou University. All the enrolled patients were operated on using the Mckeown method, and a retrospective study was conducted. Data for preoperative and postoperative test indices, intraoperative embedding materials, postoperative complications, and preoperative and postoperative treatment were collected, and the relationship between various factors and the incidence of cervical anastomotic fistula and stenosis was analysed. Univariate analysis was conducted using t tests or Fisher's exact probability method, and multivariate analysis was conducted using logistic regression models. RESULTS: All 128 patients successfully underwent surgery without dying. The enrolled patients were evaluated using the Stooler classification, with 28 patients having grade 0, 41 patients having grade 1, 34 patients having grade 2, 21 patients having grade 3, and 4 patients having grade 4 stenosis. Patients with stenosis of grade 3 or above had obvious choking sensation, which could only be relieved by balloon dilation. Symptoms in all patients with stenosis were relieved by balloon dilation. There were no significant differences between the two groups regarding embedding materials, preoperative choking history, history of alcohol consumption, history of hypertension, history of coronary heart disease, history of diabetes, postoperative calcium concentration, average albumin concentration, average platelet concentration, body mass index, anastomotic fistula, preoperative chemotherapy, postoperative chemotherapy, or postoperative cough (P>0.05). There were significant differences in postoperative reflux (χ2=11.338, P<0.05) and scar constitution (χ2=12.497, P<0.05). The effects of embedding materials in patients with anastomotic fistula were significantly different (χ2=4.372, P<0.05). CONCLUSIONS: Postoperative reflux and scar constitution may be risk factors for postoperative anastomotic stenosis after resection of esophageal cancer. There was almost no difference in the effects on esophageal anastomotic stenosis between embedding materials and the omentum majus, but Neoveil® may have certain advantages in preventing cervical anastomotic fistula, and thus may have certain clinical application value.
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MicroRNAs (miRs) have emerged as being important in cancer biology. miR191 is a conserved miRNA, which has been investigated in detail and is reported to be induced by hypoxia-inducible factor (HIF)1α and has an contributory action in the progression of breast, hepatic and pancreatic cancer. However, the effects of miR191 in the progression of lung cancer are a subject of debate. In the present study, it was found that the expression of miR-191 was significantly upregulated in nonsmall cell lung cancer (NSCLC) cells in patients in vivo. However, the levels of miR191 remained unchanged in SKMES1, A549 and NCIH460 NSCLC cell lines, compared with the level in the normal HBE lung cell line, however, the levels were markedly upregulated in these NSCLC cell lines under conditions of chronic hypoxia. Subsequently, an miR191 mimic was transfected into the NSCLC cell lines to examine its effect on the progression of the NSCLC cells in vitro. The data obtained using MTT and Cell counting kit8 assays revealed that miR191 had no effect on the proliferation of the cells under normal condition, however, their proliferation was promoted under mild hypoxic conditions. In addition, the results of a Transwell migration assay showed that miR191 had a promoting effect on NSCLC cell migration under the conditions of chronic hypoxia. Furthermore, the TargetScan bioinformatics server and 3'-untranslated region luciferase reporter assay indicated that the transcription factor, nuclear factor 1α (NFIA) was a target of miR191. Subsequent western blot analysis showed that, in chronichypoxia, the protein levels of NFIA and the tumor suppressor, CCAAT-enhancer-binding protein α, were sharply reduced in A549 cells. In conclusion, miR191 was induced by chronic hypoxia and promoted the proliferation and migration of NSCLC cells under chronic hypoxic conditions. This promotion may be associated with its targeting of NFIA. The present findings may provide a potential molecular target for the therapeutic treatment of NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , Fatores de Transcrição NFI/genética , Regiões 3' não Traduzidas , Adulto , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição NFI/metabolismo , Interferência de RNA , Transdução de SinaisRESUMO
PURPOSE: MicroRNA-454 has been proven dysregulated in some human malignancies and correlated with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to explore the effects of miR-454 in NSCLC tumorigenesis and development. METHODS: Using quantitative RT-PCR, we detected miR-454 expression in NSCLC cell lines and primary tumor tissues. The association of miR-454 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-454 on the biological behavior of NSCLC cells were investigated. At last, the potential regulatory function of miR-454 on PTEN expression was confirmed. RESULTS: miR-454 was found to be up-regulated in NSCLC tissues and cell lines. High miR-454 expression was closely correlated with lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis corroborated that miR-454 overexpression was an independent unfavourable prognostic factor for patients with NSCLC. Down-regulation of miR-454 could significantly reduce NSCLC cell proliferation, enhance cell apoptosis, and impair cell invasion and migration in vitro, while up-regulation of miR-454 showed opposite effects. Further, PTEN was confirmed as a direct target of miR-454 by using Luciferase Reporter Assay. CONCLUSIONS: These findings indicate that miR-454 may act as an oncogene in NSCLC and would serve as a potential therapy target for this disease.
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Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , Sequência de Bases , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , PTEN Fosfo-Hidrolase/metabolismo , PrognósticoAssuntos
Autofagia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Carcinoma de Células Escamosas/terapia , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas/tratamento farmacológico , HumanosRESUMO
Among malignant tumors, the mortality rate of esophageal squamous cell carcinoma (ESCC) ranks sixth in the world. Late-stage diagnosis of ESCC increases the mortality. Therefore, more effective biomarkers for early diagnosis of ESCC are necessary. Unfortunately, appropriate biomarkers for clinical diagnosis and prognosis have not been identified yet. However, recent progresses in quantitative proteomics have offered opportunities to identify plasma proteins as biomarkers for ESCC. In the present study, plasma samples were analyzed by differential in-gel electrophoresis (DIGE) and differentially expressed proteins were identified by matrix assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF MS). A total of 31 proteins representing 12 unique gene products were identified, in which 16 proteins were up-regulated and 15 down-regulated in tumors. The up-regulated proteins were alpha-2-HS-glycoprotein (AHSG), leucine-rich alpha-2-glycoprotein (LRG), zinc-alpha-2-glycoprotein, alpha-1-antichymotrypsin, complement factor I and complement C4-B, whereas the down-regulated proteins were serum albumin, Ig alpha-2 chain C region, alpha-1-antitrypsin, fibrinogen gamma chain, haptoglobin and hemoglobin subunit alpha. Among all the differentially expressed proteins, AHSG and LRG were validated by ELISA. The results were consistent with the data from the proteomics results, further suggesting that AHSG and LRG may be employed as potential biomarkers for the early diagnosis of ESCC. In summary, this study was the first time to use DIGE combined MALDI-TOF/TOF platform to identify the potential plasma biomarkers for ESCC. The plasma AHSG and LRG showed great potential for ESCC screening.
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Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Eletroforese em Gel Bidimensional/métodos , Neoplasias Esofágicas/sangue , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Ensaio de Imunoadsorção Enzimática , Carcinoma de Células Escamosas do Esôfago , Humanos , Regulação para CimaRESUMO
Inflammatory chemokine CCL20 and its receptor CCR6 have been reported to correlate with colorectal cancer patients' metastasis. However, the role of CCL20 in patients with NSCLC is not well defined. In this study, we detected the expression of CCL20 in tumor samples and corresponding adjacent ones (n=71) from patients with NSCLC using RT-PCR and observed that CCL20 showed higher expression in tumor samples (0.28±0.17) than in adjacent ones (0.20±0.13) (n=71, P=0.0056), which was also verified in protein level using IHC. Analysis results showed that CCL20 expression was positively associated with CD4 (n=80, P=0.0046), Foxp3 (n=80, P=0.0020) and IL-10 (n=61, P=0.0003) in tumor samples. And the flow data showed that Treg cells accumulated in TIL (MFI: 961±760) compared with PBMC (MFI: 683±460) (n=40, P=0.0046); and the percentage of CCR6 - the sole receptor of CCL20 - on Treg cells was higher in TIL (MFI: 1311±1268) than in PBMC (MFI: 976±780) (n=40, P=0.0219). It was interesting to find that the expression of CCL20 in tumor sites was almost 1.5-fold higher in samples from high-stage patients (III-IV stage, 0.34±0.17) compared with those from low-stage patients (I-II stage, 0.22±0.11) (P=0.0056). Furthermore, the higher expression of CCL20 was associated with a lower overall survival (P=0.0198). The IHC data showed that tumor cells were the main source of CCL20, and after treated cell line A549 with docetaxel, we found that the secretion of CCL20 was decreased heavily (n=3, P=0.0046). Our results demonstrated that CCL20 cooperated with CCR6 could recruit Treg cells to tumor sites, and chemotherapy medicine docetaxel could decrease the expression of CCL20.
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Carcinoma Pulmonar de Células não Pequenas/imunologia , Quimiocina CCL20/metabolismo , Neoplasias Pulmonares/imunologia , Receptores CCR6/metabolismo , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Quimiocina CCL20/genética , Progressão da Doença , Docetaxel , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Receptores CCR6/genética , Transdução de Sinais/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Taxoides/farmacologiaRESUMO
INTRODUCTION: Overexpression of the enhancer of zeste homolog 2 (EZH2) protein has been found in broad range of cancer types, including non-small cell lung cancer (NSCLC). Nevertheless, the mechanisms by which EZH2 becomes overexpressed in NSCLC remain unclear. MicroRNAs (miRNAs) can regulate target gene expression through translational control. In this study, we investigate whether miRNA (miR-101) regulates EZH2 expression in NSCLC. METHODS: We evaluated the expression of miR-101 and EZH2 in 20 matched NSCLC and adjacent nontumor lung tissues by reverse-transcriptase polymerase chain reaction and immunohistochemistry, respectively. Luciferase reporter assay was used to determine whether miR-101 directly targets EZH2. To assess the effect of miR-101 on NSCLC biological behavior, cell proliferation, invasion, and response to chemotherapy were analyzed using NSCLC cells transfected with miR-101 mimics or transfected with specific small interfering RNA to deplete EZH2 (small interfering RNA-EZH2). RESULTS: Reduced expression of miR-101 was associated with overexpression of EZH2 in NSCLC tumor tissues. Transfection of miR-101 mimics significantly suppressed the activity of the luciferase reporter containing wild type but not mutant EZH2 3'-UTR and decreased EZH2 expression in NSCLC cell lines. Furthermore, enforced expression of miR-101 or knockdown of EZH2 led to reduced NSCLC cell proliferation and invasion and sensitized cancer cells to paclitaxel-mediated apoptosis through inducing expression of the proapoptotic protein Bim. CONCLUSIONS: miR-101 inhibits cell proliferation and invasion and enhances paclitaxel-induced apoptosis in NSCLC cells, at least in part, by directly repressing EZH2 expression. Therapeutic strategies to rescue miR-101 expression or silence EZH2 may be beneficial to patients with NSCLC in the future.
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Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ligação a DNA/metabolismo , Neoplasias Pulmonares/genética , MicroRNAs/genética , Fatores de Transcrição/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma Bronquioloalveolar/genética , Adenocarcinoma Bronquioloalveolar/metabolismo , Adenocarcinoma Bronquioloalveolar/patologia , Apoptose , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Adesão Celular , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Proteína Potenciadora do Homólogo 2 de Zeste , Feminino , Humanos , Técnicas Imunoenzimáticas , Luciferases/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Complexo Repressor Polycomb 2 , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Células Tumorais CultivadasRESUMO
OBJECTIVE: To investigate the diphtheria antibody level in healthy population in Beijing. METHODS: 10 age groups (< 1, 1 to 4, 5 to 9, 10 to 14, 15 to 19, 20 to 24, 25 to 29, 30 to 34, 35 to 39, and > or =40) were sampled by the Multi-stage stratified sampling method in 9 districts in Beijing, and 2 003 sera from healthy population were collected. The diphtheria antibody was determined with ELISA method. RESULTS: The diphtheria antibody-positive rate was 60.26%, and the antibody concentration was 0.62 IU/ml. A trend of decreasing in the antibody concentration was observed with increasing age and years after immunization. Antibody levels were the lowest in healthy people between 25-40 years old. CONCLUSION: It was predicted that a large scale of diphtheria outbreak would not occur recently in Beijing. It is recommended that for all adults diphtheria toxoids booster immunization should be conducted every 10 years for all adults.
Assuntos
Anticorpos Antibacterianos/sangue , Difteria/sangue , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , China , Difteria/imunologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Vigilância da População , Adulto JovemRESUMO
OBJECTIVE: To evaluate the safety and epidemiological effects on the first mass vaccination program, using the China-made A (H1N1) influenza vaccine. METHODS: Descriptive epidemiology and cohort study design were used to assess the influenza A H1N1 vaccine on its safety and epidemiological effects. RESULTS: 95 244 subjects were immunized with A (H1N1) influenza vaccine. 193 adverse events were reported through AEFI Management System, with the Reported rates of AEFI as 2.03. Most of the adverse events (137/193, 71.0%) happened during the first 24 hours after immunization was carried out. Of 81 adverse reactions confirmed to be related to immunization, with 78 (96.3%) showed mild reactions. No Guillain-Barre Syndrome related to vaccination was reported through the AEFI Management System. The epidemiological protection rate of A (H1N1) vaccine could reach 80.9% when the coverage was not considered. CONCLUSION: The A (H1N1) influenza vaccine showed a similar safety profile to seasonal flu vaccine. The vaccine demonstrated a good epidemiological effects against A (H1N1) influenza virus infection.
Assuntos
Vacinas contra Influenza/efeitos adversos , Influenza Humana/prevenção & controle , Vacinação em Massa , Adolescente , Adulto , Criança , China , Estudos de Coortes , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: Using simulated outbreaks to choose the optimal model and its related parameters on measles so as to provide technical support for developing an Auto Warning System (AWS). METHODS: AEGIS-Cluster Creation Tool was applied to simulate a range of unique outbreak signals. Then these simulations were added to the actual daily counts of measles from the National Disease Surveillance System, between 2005 and 2007. Exponential weighted moving average (EWMA), C1-MILD (C1), C2-MEDIUM (C2), C3-ULTRA (C3) and space-time permutation scan statistic model were comprehensively applied to detect these simulations. Tools for evaluation as Youden' s index and detection time were calculated to optimize parameters before an optimal model was finally chosen. RESULTS: EWMA (lamda = 0.6, k = 1.0), CI (k = 0.1, H=3sigma), C2 (k = 0.1, H=3sigma), C3 (k = 1.0, H=4sigma) and space-time permutation scan statistic (maximum temporal cluster size=7 d, maximum spatial cluster size = 5 km) appeared to be the optimal parameters among these models. Youden's index of EWMA was 90.8% and detection time being 0.121 d. Youden's index of C1 was 88.7% and detection time being 0.142 d. Youden's index of C2 was 92.9% and detection time being 0.121 d. Youden's index of C3 was 87.9% and detection time being 0.058 d. Youden's index of space-time permutation scan statistic was 94.3% and detection time being 0.176 d. CONCLUSION: Among these five early warning detection models, space-time permutation scan statistic model had the highest efficacy.