RESUMO
AIM: A randomised controlled trial (RCT) was implemented to verify the feasibility and acceptability of cognitive education in the format of mind maps for increasing perceived control and decreasing the symptom distress of lung cancer patients who were receiving chemotherapy. METHODS: A total of 136 lung cancer patients who were receiving chemotherapy were randomised using stratified blocks (1:1 ratio, from March 2016 to April 2017). The intervention group was given cognitive education in the format of mind maps. The control group was provided conventional education. The primary outcomes were perceived control, including cancer experience and cancer efficacy; the secondary outcomes included symptom distress (arising from fatigue, distress, sleep disturbance, poor appetite, drowsiness, shortness of breath, etc.). The Mann-Whitney U test, chi-squared test, two-sample t test and repeated measurement analysis of variance were used. RESULTS: Ninety-four patients completed the final study. The results of the repeated measurement analysis of variance indicated that at the 8th or 12th week following cognitive education intervention in the format of mind maps, the cancer experience, cancer efficacy (except personal efficacy) and symptom distress (arising from fatigue, distress, sleep disturbance, and sadness and its total scores) of the patients in the intervention group were considerably improved compared with those of the control group (p < 0.05). The longer the intervention was, the higher the level of the patients' perceived control was and the lower the degree of patient symptom distress was (p < 0.05). CONCLUSIONS: Our findings suggest that cognitive education in the format of mind maps could improve perceived control and decrease the symptom distress of lung cancer patients who were receiving chemotherapy and that it was feasible and acceptable. Cognitive education in the format of mind maps was found to be an effective teaching tool for lung cancer patients who were receiving chemotherapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/psicologia , Controle Interno-Externo , Neoplasias Pulmonares/psicologia , Educação de Pacientes como Assunto/métodos , Angústia Psicológica , Carcinoma de Pequenas Células do Pulmão/psicologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Cognição , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/fisiopatologia , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Autoeficácia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/fisiopatologiaRESUMO
BACKGROUND Symptom distress is very common in patients with nasopharyngeal carcinoma (NPC) during radiotherapy, seriously affecting their quality of life and impeding the process of rehabilitation. Resourcefulness training can enhance the level of resourcefulness and benefit-finding, palliate symptom distress, and promote disease rehabilitation. However, the effects of resourcefulness training on local complications and benefit-finding in NPC patients during radiotherapy remains poorly understood. MATERIAL AND METHODS Questionnaires and resourcefulness training intervention were used in this study. The relationships among resourcefulness, benefit-finding, and symptom distress of 304 NPC patients were analyzed and the effects of resourcefulness training on NPC patients (N=80) were evaluated during radiotherapy. RESULTS Among the 304 NPC patients, age, educational level, occupation, family monthly income, method of payment of medical expenses, and histological types were significant factors influencing resourcefulness and benefit-finding. The patients' resourcefulness was positively correlated to their benefit-finding; and their distress was negatively correlated to their resourcefulness. After resourcefulness training for 2 months, average scores of the resourcefulness and benefit-finding were significantly increased in the intervention group (N=40) compared to those in the control group (N=40). Average scores of symptom distress were significantly reduced in the 2 groups, but they were reduced more significantly in the intervention group than in the control group. CONCLUSIONS The patients' benefit-finding and symptom distress were correlated with their resourcefulness. Resourcefulness training could enhance the level of resourcefulness and benefit-finding, palliate symptom distress, and promote disease rehabilitation in NPC patients during radiotherapy.
Assuntos
Carcinoma/psicologia , Neoplasias Nasofaríngeas/psicologia , Participação do Paciente/psicologia , Adulto , Idoso , China , Depressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Educação de Pacientes como Assunto/métodos , Participação do Paciente/métodos , Qualidade de Vida , Inquéritos e Questionários , Avaliação de Sintomas/métodos , Avaliação de Sintomas/psicologiaRESUMO
BACKGROUND: We found that selenium-binding protein 1 (SBP1) was progressively decreased in the human bronchial epithelial carcinogenic processes. Knockdown of SBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. However, the relationship between SBP1 expression and clinicopathological factors of patients has not been defined completely. The specific role of SBP1 in prognosis of lung squamous cell carcinoma (LSCC) is still unknown. METHODS: Tissue samples from 82 patients treated by pulmonary lobectomy for LSCC were used. Immunohistochemistry and western blotting were used to detect the expressions of SBP1 protein. The relationships between the expression level of SBP1 and the clinicopathological features of patients were analyzed. Cox proportional hazard regression analysis and Kaplan-Meier method were used to perform survival analysis. RESULTS: Expressions of SBP1 proteins were significantly lower in LSCC tissues than that in the corresponding normal bronchial epithelium (NBE) tissues (P = 0.000). In LSCC, The expression levels of SBP1 had not correlated with patients' age, gender, smoking state, primary tumor stages (T), TNM clinical stages, and distant metastasis (M) (P > 0.05). However, downregulation of SBP1 was significantly associated with higher lymph node metastasis and lower overall survival rate (P < 0.05). Cox regression analysis indicated low expressions of SBP1 can be an independent prognostic factor for poor overall survival in LSCC patients (P = 0.002). CONCLUSIONS: Downregulation of SBP1 may play a key role in the tumorigenic process of LSCC. SBP1 may be a novel potential prognostic factor of LSCC.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/secundário , Neoplasias Pulmonares/patologia , Proteínas de Ligação a Selênio/metabolismo , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Regulação para Baixo , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffin-embedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis. The results showed that the combination of the three proteins could perfectly discriminate NBE from preneoplastic lesions (SM, AH and CIS) from invasive LSCC, achieving a sensitivity of 96% and a specificity of 92% in discriminating NBE from preneoplatic lesions, a sensitivity of 100% and a specificity of 98% in discriminating NBE from invasive LSCC, and a sensitivity of 92% and a specificity of 91% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, we knocked down GSTP1 in immortalized human bronchial epithelial cell line 16HBE cells, and then measured their susceptibility to carcinogen benzo(a)pyrene-induced cell transformation. The results showed that GSTP1 knockdown significantly increased the efficiency of benzo(a)pyrene-induced 16HBE cell transformation. The present data first time show that GSTP1, HSPB1 and CKB are novel potential biomarkers for early detection of LSCC, and GSTP1 down-regulation is involved in human bronchial epithelial carcinogenesis.
Assuntos
Biomarcadores Tumorais/metabolismo , Detecção Precoce de Câncer , Neoplasias Pulmonares/metabolismo , Neoplasias de Células Escamosas/metabolismo , Sequência de Aminoácidos , Biomarcadores Tumorais/química , Biomarcadores Tumorais/genética , Brônquios/patologia , Linhagem Celular , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/metabolismo , Análise por Conglomerados , Creatina Quinase Forma BB/química , Creatina Quinase Forma BB/genética , Creatina Quinase Forma BB/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Expressão Gênica , Glutationa S-Transferase pi/química , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismo , Proteínas de Choque Térmico HSP27/química , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico , Humanos , Microdissecção e Captura a Laser , Neoplasias Pulmonares/diagnóstico , Chaperonas Moleculares , Dados de Sequência Molecular , Neoplasias de Células Escamosas/diagnóstico , Proteômica , Curva ROC , Estatísticas não Paramétricas , Espectrometria de Massas em TandemRESUMO
Deep vein thrombosis (DVT) is one of the common complications after joint replacement, which seriously affects the quality of life of patients. We systematically searched nine databases, a total of eleven studies on prediction models to predict DVT after knee/hip arthroplasty were included, eight prediction models for DVT after knee/hip arthroplasty were chosen and compared. The results of network meta-analysis showed the XGBoost model (SUCRA 100.0%), LASSO (SUCRA 84.8%), ANN (SUCRA 72.1%), SVM (SUCRA 53.0%), ensemble model (SUCRA 40.8%), RF (SUCRA 25.6%), LR (SUCRA 21.8%), GBT (SUCRA 1.1%), and best prediction performance is XGB (SUCRA 100%). Results show that the XGBoost model has the best predictive performance. Our study provides suggestions and directions for future research on the DVT prediction model. In the future, well-designed studies are still needed to validate this model.
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Metanálise em Rede , Complicações Pós-Operatórias , Trombose Venosa , Humanos , Trombose Venosa/etiologia , Artroplastia do Joelho/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologiaRESUMO
Background: Patients with New York Heart Association (NYHA) grade III chronic heart failure (CHF) present with low capacity for daily activities, severe self-perceived burden, and poor quality of life. Effective nursing interventions may reduce patients' self-perceived burden and improve their quality of life. Objectives: To explore the effects of an explain-simulate-practice-communicate-support intervention on the self-perceived burden, cardiac function, and activities of daily living (ADL) ability in patients with New York Heart Association grade III chronic heart failure. Methods: Of the 100 patients with New York Heart Association grade III chronic heart failure who were electronically randomized and equally divided into control and intervention groups, data from 88 patients who completed our study were analyzed. The primary outcome was quality of life; secondary outcomes were self-perceived burden, 6-min walking test distances, serum N-terminal pro-brain natriuretic peptide levels, New York Heart Association cardiac function classification, and ability to perform activities of daily living. Results: After 12 weeks' intervention, the intervention group had significantly lower self-perceived burden, Minnesota Living with Heart Failure Questionnaire scores, N-terminal pro-brain natriuretic peptide levels, and New York Heart Association grades compared with the control group, while 6-min walking test distances, left ventricular ejection fraction, and modified Barthel Index scale scores were significantly higher than those in the control group (P > 0.05). Conclusions: The explain-simulate-practice-communicate-support intervention improved patients' quality of life through reducing the level of self-perceived burden, and improving cardiac function and activities of daily living ability. This intervention was found to be effective for patients with New York Heart Association grade III chronic heart failure.
RESUMO
BACKGROUND: Exercise intervention (EI) is a promising and economical way for elderly patients with hip fracture, but the evidence regarding effective EIs remains fragmented and controversial, and it is unclear which type of exercise is optimal. The purpose of this Bayesian network meta-analysis (NMA) is to compare and rank the efficacy of various EIs in elderly patients with hip fracture. MATERIALS AND METHODS: A comprehensive literature search was performed using a systematic approach across various databases including Medline (via PubMed), CINAHL, CNKI, Web of Science, Wan Fang, Embase, VIP, Cochrane Central Register of Controlled Trials and CBM databases. The search encompasses all available records from the inception of each database until December 2022. The Inclusion literature comprises randomized controlled trials that incorporate at least one EI for elderly patients with hip fracture. We will assess the risk of bias of the studies in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, and assess each evidence of outcome quality in accordance with the Grading of Recommendations Assessment, Development and Evaluation framework. The NMA will be performed by STATA 15.0 software and OpenBUGS version 3.2.3. The identification of publication bias will be accomplished through the utilization of a funnel plot. We will rank the EIs effects according to the cumulative ranking probability curve (surface under the cumulative ranking area, SUCRA). The primary outcomes will be hip function in elderly patients, and the secondary outcomes will be activities of daily living, walking capacity and balance ability of elderly patients. TRIAL REGISTRATION: PROSPERO registration number: CRD4202022340737.
Assuntos
Atividades Cotidianas , Fraturas do Quadril , Idoso , Humanos , Teorema de Bayes , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Fraturas do Quadril/terapia , Terapia por Exercício , Metanálise como AssuntoRESUMO
The implementation of exercise intervention (EI) presents a promising and economical way for patients with hip fracture. However, the optimal type of EI remains unclear. The objective of this study is to evaluate the efficacy of various EI approaches and identify the optimal intervention for improving the prognosis of patients with hip fracture. A comprehensive search of Medline (via PubMed), Web of Science, Embase, Cochrane Central Register of Controlled Trials, CINAHL, CNKI, Wan Fang, VIP, and CBM was conducted from their earliest records to June 2022. The included randomized controlled trials (RCTs) included at least one type of exercise for patients with hip fracture. The methodological quality of these trials was assessed using the Cochrane Collaboration Risk of Bias Tool. All direct and indirect comparisons were analyzed by Stata 14.0 and OpenBUGS 3.2.3 software. The primary outcome was hip function, and the secondary outcomes were activity of daily living (ADL), walking capacity and balance ability of patients. Based on the ranking probabilities, resistance exercise (RE) was ranked as the most effective among all exercise interventions (surface under cumulative ranking curve values [SUCRA]: 94.8%, [MD]: - 11.07, [Crl]: - 15.07 to - 7.08) in improving the efficacy of patients' hip function, followed by balance exercise (BE) ([SUCRA]:81.1%, [MD]: - 8.79, [Crl]: - 13.41 to - 4.18) and muscle strength exercise ([SUCRA]:57.6%, [MD]: - 5.35, [Crl]: - 9.70 to - 0.95). For the improvement of ADL for patients with hip fracture, BE ([SUCRA]:98.4%, [MD]: - 17.38, [Crl]: - 23.77 to - 11.04) may be the best EI. The findings of this study indicate that RE and BE might be the best approach to improve prognosis for patients with hip fracture. However, further rigorous and meticulously planned RCTs are required to substantiate the conclusions drawn from this study.
Assuntos
Fraturas do Quadril , Lepidópteros , Humanos , Exercício Físico , Terapia por Exercício , Fraturas do Quadril/terapia , Metanálise em Rede , CaminhadaRESUMO
OBJECTIVE: To investigate the differential protein profile of human lung squamous carcinoma (HLSC) and normal bronchial epithelium (NBE) and provide preliminary results for further study to explore the carcinogenic mechanism of HLSC. METHODS: Laser capture microdissection (LCM) was used to purify the target cells from 10 pairs of HLSC tissues and their matched NHBE, respectively. A stable-isotope labeled strategy using iTRAQ, followed by 2D-LC/Q-STAR mass spectrometry, was performed to separate and identify the differential expression proteins. RESULTS: A total of 96 differential expression proteins in the LCM-purified HLSC and NBE were identified. Compared with NBE, 49 proteins were upregulated and 47 proteins were downregulated in HLSC. Furthermore, the expression levels of the differential proteins including HSPB1, CKB, SCCA1, S100A8, as well as S100A9 were confirmed by western blot and tissue microarray and were consistent with the results of quantitative proteomics. CONCLUSION: The different expression proteins in HLSC will provide scientific foundation for further study to explore the carcinogenic mechanism of HLSC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Microdissecção e Captura a Laser/métodos , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Proteômica/métodos , Mucosa Respiratória/metabolismo , Análise de Variância , Antígenos de Neoplasias/análise , Antígenos de Neoplasias/metabolismo , Western Blotting , Brônquios/citologia , Carcinoma de Células Escamosas/química , Feminino , Humanos , Imuno-Histoquímica , Marcação por Isótopo , Neoplasias Pulmonares/química , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Reprodutibilidade dos Testes , Mucosa Respiratória/química , Serpinas/análise , Serpinas/metabolismoRESUMO
EGFR is a potent stimulator of invasion and metastasis in head and neck squamous cell carcinomas (HNSCC). However, the mechanism by which EGFR may stimulate tumor cell invasion and metastasis still need to be elucidated. In this study, we showed that activation of EGFR by EGF in HNSCC cell line SCC10A enhanced cell migration and invasion, and induced loss of epitheloid phenotype in parallel with downregulation of E-cadherin and upregulation of N-cadherin and vimentin, indicating that EGFR promoted SCC10A cell migration and invasion possibly by an epithelial to mesenchymal transition (EMT)-like phenotype change. Interestingly, activation of EGFR by EGF induced production of matrix metalloproteinase-9 (MMP-9) and soluble E-cadherin (sE-cad), and knockdown of MMP-9 by siRNA inhibited sE-cad production induced by EGF in SCC10A. Moreover, both MMP-9 knockdown and E-cadherin overexpression inhibited cell migration and invasion induced by EGF in SCC10A. The results indicate that EGFR activation promoted cell migration and invasion through inducing MMP-9-mediated degradation of E-cadherin into sE-cad. Pharmacologic inhibition of EGFR, MEK, and PI3K kinase activity in SCC10A reduced phosphorylated levels of ERK-1/2 and AKT, production of MMP-9 and sE-cad, cell migration and invasion, and expressional changes of EMT markers (E-cadherin and N-cadherin) induced by EGF, indicating that EGFR activation promotes cell migration and invasion via ERK-1/2 and PI3K-regulated MMP-9/E-cadherin signaling pathways. Taken together, the data suggest that EGFR activation promotes HNSCC SCC10A cell migration and invasion by inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin into sE-cad related to activation of ERK-1/2 and PI3K signaling pathways.
Assuntos
Caderinas/metabolismo , Movimento Celular , Transição Epitelial-Mesenquimal , Receptores ErbB/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteólise , Carcinoma de Células Escamosas , Adesão Celular , Linhagem Celular Tumoral , Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Epidérmico/fisiologia , Receptores ErbB/agonistas , Humanos , Sistema de Sinalização das MAP Quinases , Invasividade Neoplásica , Fenótipo , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
BACKGROUND: The epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC) and is associated with pathogenesis of NPC. However, the downstream signaling proteins of EGFR in NPC have not yet been completely understood at the system level. The aim of this study was identify novel downstream proteins of EGFR signaling pathway in NPC cells. RESULTS: We analyzed EGFR-regulated phosphoproteome in NPC CNE2 cells using 2D-DIGE and mass spectrometry analysis after phosphoprotein enrichment. As a result, 33 nonredundant phosphoproteins including five known EGFR-regulated proteins and twenty-eight novel EGFR-regulated proteins in CNE2 were identified, three differential phosphoproteins were selectively validated, and two differential phosphoproteins (GSTP1 and GRB2) were showed interacted with phospho-EGFR. Bioinformatics analysis showed that 32 of 33 identified proteins contain phosphorylation modification sites, and 17 identified proteins are signaling proteins. GSTP1, one of the EGFR-regulated proteins, associated with chemoresistance was analyzed. The results showed that GSTP1 could contribute to paclitaxel resistance in EGF-stimulated CNE2 cells. Furthermore, an EGFR signaling network based on the identified EGFR-regulated phosphoproteins were constructed using Pathway Studio 5.0 software, which includes canonical and novel EGFR-regulated proteins and implicates the possible biological roles for those proteins. CONCLUSION: The data not only can extend our knowledge of canonical EGFR signaling, but also will be useful to understand the molecular mechanisms of EGFR in NPC pathogenesis and search therapeutic targets for NPC.
RESUMO
BACKGROUND: Radioresistance leads to treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, enhancing the radiosensitivity of NPC cells would likely increase the effectiveness of radiotherapy. Annexin VII (Annexin A7, ANXA7) might be a tumor promoter in NPC but its functions in radiosensitivity remain unclear. METHODS: NPC cell lines CNE2-shANXA7 and CNE2-pLKO.1 were generated and CNE2-shANXA7 nude mice xenograft tumor models were established. The main effects and molecular mechanisms of ANXA7 knockdown in NPC radiosensitivity were studied in vitro and in vivo by analyzing cell viability, clonogenicity, apoptosis, cell cycle distribution, tumor radioresponse and immunohistochemistry assay. RESULTS: ANXA7 knockdown revealed potentially enhanced NPC cell radiosensitivity via apoptosis and increased the cell number at the G2/M phase. In the xenograft model, NPC cells with ANXA7 knockdown were dramatically sensitive to irradiation and tumor growth was significantly suppressed. Compared to CNE2-pLKO.1 xenografts, CNE2-shANXA7 showed more γ-H2AX foci and less phospho-DNA PKcs. CONCLUSIONS: ANXA7 knockdown increased the radiosensitivity of NPC by enhancing apoptosis, modulating the cell cycle distribution into more radiosensitive phases, promoting DNA damage, and inhibiting repair. We showed that decreased ANXA7 levels enhanced radiosensitivity and provided insights into the therapeutic targets for NPC radiotherapy.
Assuntos
Anexina A7/metabolismo , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Animais , Anexina A7/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Nasofaringe/patologia , RNA Interferente Pequeno/metabolismo , Tolerância a Radiação/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Radiotherapy is the primary treatment for nasopharyngeal carcinoma while radioresistance can hinder efficient treatment. To explore the role of annexin A1 and its potential mechanisms in radioresistance of nasopharyngeal carcinoma, human nasopharyngeal carcinoma cell line CNE2-sh annexin A1 (knockdown of annexin A1) and the control cell line CNE2-pLKO.1 were constituted and CNE2-sh annexin A1 xenograft mouse model was generated. The effect of annexin A1 knockdown on the growth of xenograft tumor after irradiation and radiation-induced DNA damage and repair was analyzed. The results of immunohistochemistry assays and Western blotting showed that the level of annexin A1 was significantly downregulated in the radioresistant nasopharyngeal carcinoma tissues or cell line compared to the radiosensitive nasopharyngeal carcinoma tissues or cell line. Knockdown of annexin A1 significantly promoted CNE2-sh annexin A1 xenograft tumor growth compared to the control groups after irradiation. Moreover, the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays revealed that knockdown of annexin A1 significantly inhibited apoptosis in vivo compared to the control groups. We assessed the intracellular reactive oxygen species levels and the extent of radiation-induced DNA damage and repair using reactive oxygen species assay, comet assays, and immunohistochemistry assay. The results showed that knockdown of annexin A1 remarkedly reduced the intracellular reactive oxygen species levels, level of DNA double-strand breaks, and the phosphorylation level of H2AX and increased the accumulation of DNA-dependent protein kinase in nasopharyngeal carcinoma cells after irradiation. The findings suggest that knockdown of annexin A1 inhibits DNA damage via decreasing the generation of intracellular reactive oxygen species and the formation of γ-H2AX and promotes DNA repair via increasing DNA-dependent protein kinase activity and therefore improves the radioresistance in nasopharyngeal carcinoma cells. Together, our findings suggest that knockdown of annexin A1 promotes radioresistance in nasopharyngeal carcinoma and provides insights into therapeutic targets for nasopharyngeal carcinoma radiotherapy.
Assuntos
Anexina A1/genética , Apoptose/genética , Carcinoma Nasofaríngeo/genética , Tolerância a Radiação/genética , Adulto , Idoso , Animais , Anexina A1/metabolismo , Biomarcadores , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Dano ao DNA , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Histonas/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Gradação de Tumores , Estadiamento de Neoplasias , Interferência de RNA , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but radioresistance often remains an obstacle to successful treatment. In our previous study, it was demonstrated that Annexin A1 (ANXA1) was involved in the p53-mediated radioresponse in NPC cells, which suggested that it may be associated with radioresistance in NPC; however, the role of ANXA1 in NPC radioresistance is unknown. In the present study, CNE2 cells were stably transfected with pLKO.1-ANXA1-small hairpin (sh)RNAs to investigate the effects of ANXA1 on the radiosensitivity of NPC. CNE2 cells transfected with pLKO.1 were used as the control. The radiosensitivities of the cells in vitro were analyzed using the clonogenic survival assay, cell growth analysis, flow cytometry and Hoechst 33258 staining. ANXA1 downregulation significantly enhanced clonogenic survival and cell growth following treatment of CNE2 cells with ionizing radiation (IR), increased the number of cells in the S phase and decreased IR-induced apoptosis. These results suggested that the radiosensitivity of CNE2 cells transfected with ANXA1-specific shRNA was significantly lower compared with the control cells. Therefore, ANXA1 downregulation may be involved in the radioresistance of NPC, and ANXA1 may be considered a novel biomarker for predicting NPC response to radiotherapy.
RESUMO
OBJECTIVE: To amplify and sequence the partial gene coding for mucin-like protein from Chinese isolates of Schistosoma japonicum (SjMLP). METHODS: The antigenic determinants of SmMLP were predicted by PCGENE software and specific oligonucleotide primers were designed and synthesized. Total RNA was isolated from adult worms of S. japonicum using Trizol reagent and the coding region gene of SjMLP was amplified by RT-PCR technique. RESULTS: The coding region of SjMLP gene was specifically amplified by RT-PCR and the size of amplified fragment was 756 base pairs. The DNA sequence analysis result indicated that the coding sequence of the MLP was highly homologous between S. mansoni and S. japonicum. CONCLUSION: The amplified fragment is consistent to the predicted one, providing a basis for cloning and further study on DNA immunization.
Assuntos
Antígenos de Helmintos/genética , Mucinas/genética , Schistosoma japonicum/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Camundongos , Dados de Sequência Molecular , Técnicas de Amplificação de Ácido Nucleico , Proteínas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Vacinas de DNA/genéticaRESUMO
Nasopharyngeal carcinoma (NPC) has a highly increased incidence rate (20/100,000) in Southern regions of China, while being rare in the rest of the world. NPC is a malignant type of cancer due to its high occurrence rate of metastasis; however, biomarkers for effective diagnosis and treatment are yet to be identified. Annexin A1 is a glucocorticoidregulated member of a large superfamily of calcium and phospholipidbinding proteins and has been shown to have important roles in tumor development and progression, and was demonstrated to be a prognostic biomarker for head and neck cancer types. A previous study by our group showed that Annexin A1 was decreased in NPC tissue as compared with normal adjacent tissue. To investigate whether Annexin A1 is a potential biomarker for NPC, the present study assessed the effect of the Annexin A1 on the biological behavior (i.e., invasion and metastasis) of the highly metastatic NPC cell line 58F and the nonmetastatic NPC cell line 610B. The expression levels of Annexin A1 in the above two cell lines were determined by western blot analysis. Next, the recombinant plasmid pEGFPC1Annexin A1 and the small interfering (si)RNA plasmid pRNATU6.1Annexin A1 were used and stably transfected into 58F and 610B cells, respectively. These established recombinant cell lines were then used to study the up- and downregulation of Annexin A1, respectively. The correlation of Annexin A1 expression levels with the biological behavior of NPC cell lines was analyzed using a cell proliferation assay, flow cytometry, soft agar colony formation assay, as well as Transwell invasion and migration assays. The results demonstrated that upregulation of Annexin A1 suppressed the proliferation, invasion and migration of NPC cells, while downregulation of Annexin A1 promoted the proliferation, invasion and migration of NPC cells. These findings suggested that Annexin A1 may be a potential biomarker for the development and prognosis of NPC, and its dysregulation may have an important role in its underlying pathogenesis.
Assuntos
Anexina A1/genética , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Biomarcadores Tumorais/genética , Carcinoma , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo/genética , Humanos , Carcinoma Nasofaríngeo , Prognóstico , RNA Interferente Pequeno/genética , Regulação para Cima/genéticaRESUMO
BACKGROUND: Preclinical evaluation of the anti-neoplastic activity of antisense oligonucleotide (AS) suppression of human insulin-like growth factor I receptor (IGF-IR) in human epithelial ovarian cancer (EOC). METHODS: Ovarian cancer cells from 36 patients with EOC were investigated under serum-free tissue culture conditions. IGF-I production was evaluated by standard ELISA. IGF-IR and phosphorylated IRS-1, AKT, and MAP kinase expression and protein levels were evaluated by immunohistochemistry and Western blotting. Cancer cell growth and proliferation assays were performed in triplicates using MTT assay. Apoptosis was evaluated by TUNNEL assay. RESULTS: All ovarian cancer tissue samples tested produced IGF-I and expressed IGF-IR, supporting the existence of an autocrine loop. Treatment of primary ovarian cancer cell lines with an IGF-1R AS inhibited growth and proliferation and decreased clonogenicity in soft agar assay. AS treatment was demonstrated to inhibit the expression of IGF-1R and decrease the concentration of phosphorylated IRS-1, AKT, and MAP kinase signaling protein downstream of the IGF-IR. We also observed that the IGF-1R AS sensitized cancer cell lines to cisplatin in vitro through the PI3K pathway. CONCLUSIONS: IGF-IR enhances the proliferation and tumorigenicity of human ovarian cancer cells and inhibition of IGF-IR by AS oligonucleotide treatment potentiates the activity of cisplatin in vitro. Therefore, IGF-1R is a potential molecular target in ovarian cancer.
RESUMO
BACKGROUND: Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1) was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC) carcinogenesis. METHODS: iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium) from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(a)pyrene (B[a]P)-induced human bronchial epithelial cell transformation were determined. RESULTS: 102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. CONCLUSIONS: The present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.
Assuntos
Brônquios/patologia , Carcinoma de Células Escamosas/metabolismo , Transformação Celular Neoplásica/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Ligação a Selênio/genética , Sequência de Aminoácidos , Apoptose , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Ciclo Celular , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Regulação para Baixo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Microdissecção e Captura a Laser , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Dados de Sequência Molecular , Proteoma/genética , Proteoma/metabolismo , Curva ROC , Mucosa Respiratória/patologia , Proteínas de Ligação a Selênio/química , Proteínas de Ligação a Selênio/metabolismo , Espectrometria de Massas em TandemRESUMO
Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but radioresistance remains a serious obstacle to successful treatment in many cases. Therefore, the biomarkers for predicting NPC response to radiotherapy are very important for targeted therapy and individualized radiotherapy of NPC. Accumulating evidences have shown that Annexin A1 was correlated with NPC radioresistance. First, Annexin A1 is a potential tumor suppressor gene, and can regulate tumor cell proliferation and apoptosis, thus abnormal expression of Annexin A1 in NPC affects apoptosis of tumor cells induced by ionizing radiation and radiotherapeutic efficacy. Second, Annexin A1 is one of the proteins that are involved in p53-mediated radioresponse in NPC, and it might be related to NPC radioresistance. Third, the expression level of Annexin A1 is down-regulated in NPC, and is correlated with metastasis, recurrence and poor prognosis of NPC, thus Annexin A1 downregulation may increase NPC radioresistance, leading to poor prognosis. Last but not the least, Annexin A1 is closely related with tumor chemoresistance, whereas radioresistance is similar to chemoresistance in many aspects, thus Annexin A1 may also be involved in NPC radioresistance. Based on the above mentions, we hypothesize that Annexin A1 is closely correlated with NPC radioresistance and is an important new biomarker for predicting NPC response to radiotherapy.
Assuntos
Anexina A1/análise , Biomarcadores Tumorais/análise , Neoplasias Nasofaríngeas/radioterapia , Radioterapia/normas , Humanos , Neoplasias Nasofaríngeas/metabolismoRESUMO
To discover novel lung adenocarcinoma (AdC) biomarkers, isobaric tags for relative and absolute quantitation (iTRAQ)-tagging combined with 2D-LC-MS/MS analysis was used to identify differentially expressed plasma membrane proteins in lung AdC and paired paraneoplastic normal lung tissues (PNLTs) adjacent to tumors. In this study, significant caveolin-1 downregulation and integrin ß1 upregulation was observed in primary lung AdC vs. PNLT. As there has been no report on the association of integrin ß1 with lung AdC, immunohistochemical staining was performed to detect the expression of integrin ß1 in an independent set of archival tissue specimens including 42 cases of PLNT, 46 cases of without lymph node metastasis primary AdC (non-LNM AdC) and 62 cases of LNM AdC; the correlation of their expression levels with clinicopathological characteristics and clinical outcomes were evaluated. Based on the data, upregulation of integrin ß1 was significantly correlated with advanced clinical stage and lymph node metastasis. Integrin ß1 overexpression was significantly associated with advanced clinical stage (P<0.05), lymph node metastasis (P<0.05), increased relapse rate (P<0.05) and decreased overall survival (P<0.05) in AdCs. Cox regression analysis indicated that integrin ß1 overexpression is an independent prognostic factor. The data suggest that integrin ß1 is a potential biomarker for LNM and prognosis of AdC and integrin ß1 upregulation may play an important role in the pathogenesis of AdC.