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[PMID]: 27775692 [Au] Autor: Aeffner F; Martin NT; Peljto M; Black JC; Major JK; Jangani M; Ports MO; Krueger JS; Young GD [Ad] Endereço: Flagship Biosciences Inc., Westminster, CO, USA. [Ti] Título: Quantitative assessment of pancreatic cancer precursor lesions in IHC-stained tissue with a tissue image analysis platform. [So] Source: Lab Invest;96(12):1327-1336, 2016 12. [Is] ISSN: 1530-0307 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Tissue image analysis (tIA) is emerging as a powerful tool for quantifying biomarker expression and distribution in complex diseases and tissues. Pancreatic ductal adenocarcinoma (PDAC) develops in a highly complex and heterogeneous tissue environment and, generally, has a very poor prognosis. Early detection of PDAC is confounded by limited knowledge of the pre-neoplastic disease stages and limited methods to quantitatively assess disease heterogeneity. We sought to develop a tIA approach to assess the most common PDAC precursor lesions, pancreatic intraepithelial neoplasia (PanIN), in tissues from Kras ; Trp53 ; Pdx-Cre (KPC) mice, a validated model of PDAC development. tIA profiling of training regions of PanIN and tumor microenvironment (TME) cells was utilized to guide identification of PanIN/TME tissue compartment stratification criteria. A custom CellMap algorithm implementing these criteria was applied to whole-slide images of KPC mice pancreata sections to quantify p53 and Ki-67 biomarker staining in each tissue compartment as a proof-of-concept for the algorithm platform. The algorithm robustly identified a higher percentage of p53-positive cells in PanIN lesions relative to the TME, whereas no difference was observed for Ki-67. Ki-67 expression was also quantified in a human pancreatic tissue sample available to demonstrate the translatability of the CellMap algorithm to human samples. Together, our data demonstrated the utility of CellMap to enable objective and quantitative assessments, across entire tissue sections, of PDAC precursor lesions in preclinical and clinical models of this disease to support efforts leading to novel insights into disease progression, diagnostic markers, and potential therapeutic targets. [Mh] Termos MeSH primário: Adenocarcinoma in Situ/diagnóstico Carcinoma Ductal Pancreático/diagnóstico Pâncreas/patologia Neoplasias Pancreáticas/diagnóstico Lesões Pré-Cancerosas/diagnóstico Proteína Supressora de Tumor p53/metabolismo [Mh] Termos MeSH secundário: Adenocarcinoma in Situ/diagnóstico por imagem Adenocarcinoma in Situ/metabolismo Adenocarcinoma in Situ/patologia Algoritmos Animais Automação Laboratorial Carcinoma Ductal Pancreático/diagnóstico por imagem Carcinoma Ductal Pancreático/metabolismo Carcinoma Ductal Pancreático/patologia Cruzamentos Genéticos Modelos Animais de Doenças Detecção Precoce de Câncer/métodos Seres Humanos Processamento de Imagem Assistida por Computador Imuno-Histoquímica Antígeno Ki-67/metabolismo Camundongos Mutantes Camundongos Transgênicos Pâncreas/metabolismo Neoplasias Pancreáticas/diagnóstico por imagem Neoplasias Pancreáticas/metabolismo Neoplasias Pancreáticas/patologia Lesões Pré-Cancerosas/diagnóstico por imagem Lesões Pré-Cancerosas/metabolismo Lesões Pré-Cancerosas/patologia Software Organismos Livres de Patógenos Específicos Bancos de Tecidos Ultrassonografia [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Ki-67 Antigen); 0 (Tumor Suppressor Protein p53) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 180306 [Lr] Data última revisão: 180306 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161025 [St] Status: MEDLINE [do] DOI: 10.1038/labinvest.2016.111

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[PMID]: 29352278 [Au] Autor: Teame H; Addissie A; Ayele W; Hirpa S; Gebremariam A; Gebreheat G; Jemal A [Ad] Endereço: Department of Public Health, College of Medicine and Health Sciences, Adigrat University, Adigrat, Ethiopia. [Ti] Título: Factors associated with cervical precancerous lesions among women screened for cervical cancer in Addis Ababa, Ethiopia: A case control study. [So] Source: PLoS One;13(1):e0191506, 2018. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: Cervical cancer is the second most prevalent cancer among women in the developing countries including Ethiopia. Precancerous lesions can be developed and risk to the development of cervical cancer over time. Early identification of the precancerous lesion and its risk factor is paramount in preventing cervical cancer. However, the determinants of cervical precancerous lesions are not well documented in Ethiopia. Therefore, this study is conducted to determine factors associated with cervical precancerous lesion among women screened for cervical cancer. METHODS: A hospital-based unmatched case-control study was conducted in selected health facilities in Addis Ababa from March to April 2016. Data were collected from 114 cases and 229 controls using an interviewer-administered questionnaire, entered to Epi Info version 7, and exported to SPSS version 20 for analysis. Odds ratios with its 95% confidence intervals and two-tailed P-value were calculated. Variables with P-value ≤ 0.2 in the bivariate analysis were included in the multivariate logistic regression model. RESULTS: Women aged 40-49 years had 2.4-fold higher odds of precancerous lesions compared to those aged 30-39 (Adjusted Odds Ratio = 2.4, 95% Confidence Interval: 1.27-4.54). Women having history of sexually transmitted infections were significantly associated with cervical precancerous lesion compared to their counterparts (Adjusted Odds Ratio = 3.20, 95% Confidence Interval: 1.26-8.10). Similarly, those women who had two or more lifetime sexual partners (Adjusted Odds Ratio = 2.17 95% Confidence Interval: 1.01-4.67), and women whose husbands had two or more lifetime sexual partners (Adjusted Odds Ratio = 3.03, 95% Confidence Interval: 1.25, 7.33) had higher odds of cervical precancerous lesions. CONCLUSIONS: Older age, history of multiple sexual partners and sexual transmitted infections were associated with increased risk of precancerous lesion. Therefore, women with higher risk of precancerous lesions should be encouraged to be screened more frequently for cervical cancer. [Mh] Termos MeSH primário: Lesões Pré-Cancerosas/epidemiologia Neoplasias do Colo do Útero/epidemiologia [Mh] Termos MeSH secundário: Ácido Acético Adulto Fatores Etários Estudos de Casos e Controles Etiópia/epidemiologia Feminino Seres Humanos Modelos Logísticos Programas de Rastreamento/métodos Meia-Idade Razão de Chances Lesões Pré-Cancerosas/diagnóstico Prevalência Fatores de Risco Comportamento Sexual Parceiros Sexuais Neoplasias do Colo do Útero/diagnóstico Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: Q40Q9N063P (Acetic Acid) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180226 [Lr] Data última revisão: 180226 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180121 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0191506

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[PMID]: 29372685 [Au] Autor: Fialkova V; Vidomanova E; Balharek T; Marcinek J; Kudela E; Hanysova S; Visnovsky J; Dobrota D; Hatok J [Ad] Endereço: Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. hatok@jfmed.uniba.sk. [Ti] Título: DNA methylation as mechanism of apoptotic resistance development in endometrial cancer patients. [So] Source: Gen Physiol Biophys;36(5):521-529, 2017 Dec. [Is] ISSN: 0231-5882 [Cp] País de publicação: Slovakia [La] Idioma: eng [Ab] Resumo: DNA methylation is a significant epigenetic modification which plays a key role in regulation of gene expression and influences functional changes in endometrial tissue. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients. The aim of our study was to examine the promoter DNA methylation changes in 22 apoptosis-associated genes in endometrioid endometrial cancer patients, precancerous lesions and healthy tissue from various normal menstrual cycle phases using a unique pre-designed methylation platform. We observed as the first a significant difference in promoter DNA methylation status in genes: BCL2L11 (p < 0.001), CIDEB (p < 0.03) and GADD45A (p < 0.05) during endometrial carcinogenesis and BIK gene (p < 0.03) in different phases of normal menstrual cycle. The results of our study indicate that deregulation of mitochondrial apoptotic pathway can considerably contributes to the apoptosis resistance development and may be helpful in identifying of new potent biomarkers in endometrial cancer. [Mh] Termos MeSH primário: Proteínas Reguladoras de Apoptose/genética Apoptose/genética Metilação de DNA/genética DNA de Neoplasias/genética Neoplasias do Endométrio/genética Epigênese Genética/genética Lesões Pré-Cancerosas/genética [Mh] Termos MeSH secundário: Adulto Idoso Carcinogênese/genética Feminino Predisposição Genética para Doença/genética Seres Humanos Meia-Idade Polimorfismo de Nucleotídeo Único/genética Eslováquia [Pt] Tipo de publicação: JOURNAL ARTICLE; MULTICENTER STUDY [Nm] Nome de substância: 0 (Apoptosis Regulatory Proteins); 0 (DNA, Neoplasm) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180223 [Lr] Data última revisão: 180223 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180127 [St] Status: MEDLINE [do] DOI: 10.4149/gpb_2017032

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[PMID]: 29284780 [Au] Autor: Herrera-Covarrubias D; Coria-Avila G; Hernandez ME; Ismail N [Ad] Endereço: School of Psychology, University of Ottawa, Ottawa K1N 6N5, ON, Canada. [Ti] Título: Stress during puberty facilitates precancerous prostate lesions in adult rats. [So] Source: Exp Oncol;39(4):269-275, 2017 Dec. [Is] ISSN: 1812-9269 [Cp] País de publicação: Ukraine [La] Idioma: eng [Ab] Resumo: Puberty can be a critical period for the long-term development of diseases, especially for stress-related disorders that depend on neuroendocrine and immune responses. Some organs like the prostate are prone to diseases that result from neuroendocrine or immune challenges, such as cancer. AIM: In the present study, we assessed the long-term effects of an acute pubertal stressor (immune-challenge) on the development of precancerous lesions in adult rats, and compared them with testosterone-induced prostatic lesions. MATERIALS AND METHODS: Pubertal male rats received a single injection of lipopolysaccharide (LPS) or saline during puberty (5 weeks old). At adulthood (8 weeks old) males were subcutaneously implanted with either an empty capsule or filled with testosterone propionate (100 mg/kg). This resulted in a total of five groups: 1) intact untreated, 2) saline-treated and implanted with a blank capsule, 3) saline-treated and implanted with a testosterone capsule, 4) LPS-treated and implanted with a blank capsule, 5) LPS-treated and implanted with a testosterone capsule. Four weeks later, the rats were sacrified and their prostates processed for histology (hematoxylin and eosin stain) and blood serum processed for hormone analysis (testosterone and corticosterone). RESULTS: Males treated with LPS (stressed during puberty via immune challenge) expressed epithelium dysplasia (specially in the ventral prostate), anisocytosis, presence of mononuclear cells, anisokariosis, non-basal polarity, abnormal nucleus-cytoplasm ratio, proplastic myoepithelium, and granular content in the lumen. These histological alterations were similar, but less severe than those observed in males implanted with testosterone during adulthood. CONCLUSION: These results indicate that pubertal exposure to an immune challenge (stress) facilitates the long-term development of prostatic lesions in adult male rats. [Mh] Termos MeSH primário: Lesões Pré-Cancerosas Neoplasias da Próstata Maturidade Sexual Estresse Fisiológico [Mh] Termos MeSH secundário: Animais Masculino Lesões Pré-Cancerosas/etiologia Lesões Pré-Cancerosas/patologia Neoplasias da Próstata/etiologia Neoplasias da Próstata/patologia Ratos Ratos Wistar [Pt] Tipo de publicação: JOURNAL ARTICLE [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180223 [Lr] Data última revisão: 180223 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171230 [St] Status: MEDLINE

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[PMID]: 28450390 [Au] Autor: East JE; Atkin WS; Bateman AC; Clark SK; Dolwani S; Ket SN; Leedham SJ; Phull PS; Rutter MD; Shepherd NA; Tomlinson I; Rees CJ [Ad] Endereço: Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. [Ti] Título: British Society of Gastroenterology position statement on serrated polyps in the colon and rectum. [So] Source: Gut;66(7):1181-1196, 2017 07. [Is] ISSN: 1468-3288 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Serrated polyps have been recognised in the last decade as important premalignant lesions accounting for between 15% and 30% of colorectal cancers. There is therefore a clinical need for guidance on how to manage these lesions; however, the evidence base is limited. A working group was commission by the British Society of Gastroenterology (BSG) Endoscopy section to review the available evidence and develop a position statement to provide clinical guidance until the evidence becomes available to support a formal guideline. The scope of the position statement was wide-ranging and included: evidence that serrated lesions have premalignant potential; detection and resection of serrated lesions; surveillance strategies after detection of serrated lesions; special situations-serrated polyposis syndrome (including surgery) and serrated lesions in colitis; education, audit and benchmarks and research questions. Statements on these issues were proposed where the evidence was deemed sufficient, and re-evaluated modified via a Delphi process until >80% agreement was reached. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool was used to assess the strength of evidence and strength of recommendation for finalised statements. : we suggest that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions (SSLs) that appear associated with a higher risk of future neoplasia or colorectal cancer (SSLs ≥10 mm or serrated lesions harbouring dysplasia including traditional serrated adenomas) should be offered a one-off colonoscopic surveillance examination at 3 years ( ). [Mh] Termos MeSH primário: Pólipos do Colo/diagnóstico Pólipos do Colo/cirurgia Pólipos/diagnóstico Pólipos/cirurgia Doenças Retais/diagnóstico Doenças Retais/cirurgia [Mh] Termos MeSH secundário: Adenoma/diagnóstico Adenoma/genética Adenoma/cirurgia Polipose Adenomatosa do Colo/diagnóstico Benchmarking Biomarcadores/análise Transformação Celular Neoplásica Colite/complicações Pólipos do Colo/genética Colonoscopia Ilhas de CpG/genética DNA/isolamento & purificação Metilação de DNA Fezes/química Seres Humanos Parassimpatolíticos/uso terapêutico Pólipos/genética Lesões Pré-Cancerosas/diagnóstico Lesões Pré-Cancerosas/cirurgia Doenças Retais/genética Terminologia como Assunto Conduta Expectante [Pt] Tipo de publicação: JOURNAL ARTICLE; PRACTICE GUIDELINE; REVIEW [Nm] Nome de substância: 0 (Biomarkers); 0 (Parasympatholytics); 9007-49-2 (DNA) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 180222 [Lr] Data última revisão: 180222 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170429 [St] Status: MEDLINE [do] DOI: 10.1136/gutjnl-2017-314005

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[PMID]: 29216866 [Au] Autor: Pritchett NR; Burgert SL; Murphy GA; Brockman JD; White RE; Lando J; Chepkwony R; Topazian MD; Abnet CC; Dawsey SM; Mwachiro MM [Ad] Endereço: National Cancer Institute, Bethesda, MD, USA. natalie.pritchett@nih.gov. [Ti] Título: Cross sectional study of serum selenium concentration and esophageal squamous dysplasia in western Kenya. [So] Source: BMC Cancer;17(1):835, 2017 12 08. [Is] ISSN: 1471-2407 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Low serum selenium status has been associated with increased risk of esophageal squamous cell carcinoma (ESCC). East Africa is a region of high ESCC incidence and is known to have low soil selenium levels, but this association has not previously been evaluated. In this study we assessed the association of serum selenium concentration and the prevalence of esophageal squamous dysplasia (ESD), the precursor lesion of ESCC, in a cross-sectional study of subjects from Bomet, Kenya. METHODS: 294 asymptomatic adult residents of Bomet, Kenya completed questionnaires and underwent endoscopy with Lugol's iodine staining and biopsy for detection of ESD. Serum selenium concentrations were measured by instrumental neutron activation analysis. Odds ratios (OR) and confidence intervals (95% CI) for associations between serum selenium and ESD were calculated using unconditional logistic regression. RESULTS: The mean serum selenium concentration was 85.5 (±28.3) µg/L. Forty-two ESD cases were identified (14% of those screened), including 5 (12%) in selenium quartile 1 (Q1), 5 (12%) in Q2, 15 (36%) in Q3, and 17 (40%) in Q4. Higher serum selenium was associated with prevalence of ESD (Q4 vs Q1: OR: 3.03; 95% CI: 1.05-8.74) and this association remained after adjusting for potential confounders (Q4 vs Q1: OR: 3.87; 95% CI: 1.06-14.19). CONCLUSION: This is the first study to evaluate the association of serum selenium concentration and esophageal squamous dysplasia in an African population at high risk for ESCC. We found a positive association between higher serum selenium concentration and prevalence of ESD, an association contrary to our original hypothesis. Further work is needed to better understand the role of selenium in the etiology of ESCC in this region, and to develop effective ESCC prevention and control strategies. [Mh] Termos MeSH primário: Carcinoma de Células Escamosas/epidemiologia Neoplasias Esofágicas/epidemiologia Lesões Pré-Cancerosas/epidemiologia Selênio/sangue [Mh] Termos MeSH secundário: Estudos Transversais Feminino Seres Humanos Quênia/epidemiologia Masculino Meia-Idade [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Nm] Nome de substância: H6241UJ22B (Selenium) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180217 [Lr] Data última revisão: 180217 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171209 [St] Status: MEDLINE [do] DOI: 10.1186/s12885-017-3837-9

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[PMID]: 29350503 [Au] Autor: Golubovic M; Lopicic M; Terzic N; Durovic M; Mugosa B; Mijovic G [Ti] Título: Presence of histopathological premalignant lesions and infection caused by high-risk genotypes of human papillomavirus in patients with suspicious cytological and colposcopy results: A prospective study. [So] Source: Vojnosanit Pregl;74(1):24-30, 2017 Jan. [Is] ISSN: 0042-8450 [Cp] País de publicação: Serbia [La] Idioma: eng [Ab] Resumo: Background/Aim: In patients with premalignant cervical lesions, human papillomavirus (HPV) infection, at any moment, may be spontaneously eliminated, or may persist or transform cervical epithelium from a lower to a higher degree. Due to that, it is necessary to wisely select the patients who are at high risk of cancer development. The aim of the study was to establish the interdependence between a suspicious Papanicolaou (Pap) test and colposcopy with the infection caused by high-risk genotypes of human papillomavirus and the presence of premalignant cervical lesions. Methods: This prospective study used cytological, colposcopy, real-time polymerase chain reaction (PCR) of high-risk genotypes of human papillomavirus and histopathological analysis of cervical biopsy specimen. Out of 2,578 female patients sent to cytological analyses in Clinical Center of Montenegro, during 2012, 2013 and 2014, the study included 80 women who had to submit their biopsy specimens due to a suspicious Pap test and atypical colposcopy results. Results: In the group of 80 (3.1%; n = 80/2,578) of the selected female patients with suspicious Pap test and colposcopy, 2/3 or 56 (70%) of them had cervicitis, and 1/3 or 24 (30%) had cervical intraepithelial neoplasia. The most common type in cervical intraepithelial neoplasia was HPV16 in 8 female patients, ie 61.53% out of the number of infected, or 33.33% out of the total number of premalignant lesions Conclusion: Patients with suspicious Papanicolaou test, colposcopy results and infection which is caused by high-risk HPV infection (HPV 16 in particular) often have premalignant cervical lesions. In these cases, histopathological confirmation of lesions is mandatory, since it serves as a definitive diagnostic procedure. [Mh] Termos MeSH primário: Células Escamosas Atípicas do Colo do Útero/patologia Neoplasia Intraepitelial Cervical/patologia Colposcopia DNA Viral/genética Testes de DNA para Papilomavírus Humano Teste de Papanicolaou Papillomaviridae/genética Infecções por Papillomavirus/virologia Lesões Pré-Cancerosas/patologia Lesões Intraepiteliais Escamosas Cervicais/patologia Neoplasias do Colo do Útero/patologia Esfregaço Vaginal [Mh] Termos MeSH secundário: Adolescente Adulto Idoso Células Escamosas Atípicas do Colo do Útero/virologia Biópsia Neoplasia Intraepitelial Cervical/virologia Criança Pré-Escolar Feminino Genótipo Seres Humanos Lactente Meia-Idade Estadiamento de Neoplasias Infecções por Papillomavirus/patologia Lesões Pré-Cancerosas/virologia Valor Preditivo dos Testes Estudos Prospectivos Reação em Cadeia da Polimerase em Tempo Real Lesões Intraepiteliais Escamosas Cervicais/virologia Neoplasias do Colo do Útero/virologia Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (DNA, Viral) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180213 [Lr] Data última revisão: 180213 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180120 [St] Status: MEDLINE [do] DOI: 10.2298/VSP150205143G

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[PMID]: 29275566 [Au] Autor: Qi MC; Chen H; Wang LP; Zhang M; Tang XF [Ad] Endereço: Institute of Dental Research, Capital Medical University School of Stomatology, Beijing 100050, China. [Ti] Título: [Interaction between transcriptional factor E26 transformation specific 1 and peroxiredoxin 1 in nicotine-induced oral precancerous lesion cells]. [So] Source: Zhonghua Kou Qiang Yi Xue Za Zhi;52(12):729-734, 2017 Dec 09. [Is] ISSN: 1002-0098 [Cp] País de publicação: China [La] Idioma: chi [Ab] Resumo: To investigate the interaction between nuclear transcriptional factor E26 transformation specific 1 (Ets1) and peroxiredoxin 1 (Prx1) in nicotine-induced oral precancerous lesion cells. Human oral precancerous lesion dysplastic oral keratinocyte (DOK) cells were cultured and divided into nicotine group, control group, knockdown group and knockdown control group. The nicotine group, knockdown group and knockdown control group were treated with 1 µmol/L nicotine for 7 days while the control group was untreated. Western blotting, co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) were performed to detect Prx1 and Ets1 protein expression, Prx1 and Ets1 protein interaction, combined activity of Ets1 with PRDX1 gene promoter region in nicotine group and control group DOK cells. In nicotine group, DOK cells were transfected with siRNA or lentivirus to knockdown Ets1 and Prx1 expression. Prx1 and Ets1 protein expression was examined by Western blotting. Nicotine increased the expression of Prx1 and Ets1 protein in DOK cells. The relative expression of Prx1 and Ets1 was 0.71±0.02, 0.12±0.01 in nicotine group and 0.53±0.06, 0.01±0.01 in control group ( 0.009, 0.000). Co-IP showed that Prx1 could form protein complex with Ets1. The expression of Prx1 and Ets1 complex protein was increased in nicotine group. ChIP revealed that nicotine upregulated the combination of transcriptional factor Ets1 with PRDX1 gene promoter region, and the enrichment fold was 80.9±19.7 in nicotine group and 13.8±1.2 in control group ( 0.004). Ets1 and Prx1 protein expression was knocked down. The relative expression of Ets1 and Prx1 was 0.60±0.06, 0.48±0.03 in knockdown group and 0.83±0.08, 0.80±0.06 in knockdown control group ( 0.016, 0.002). Ets1 knockdown suppressed the expression of Prx1 ( 0.002). Conversely, Prx1 knockdown also inhibited the expression of Ets1 significantly ( 0.000). In oral precancerous lesion cells, Ets1 directly regulates Prx1 expression and nicotine might promote the development of oral precancerous lesion by magnifying the positive feedback signal pathway between Ets1 and Prx1. [Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo Neoplasias Bucais/metabolismo Proteínas Nucleares/metabolismo Peroxirredoxinas/metabolismo Lesões Pré-Cancerosas/metabolismo [Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/genética Carcinógenos Técnicas de Silenciamento de Genes Seres Humanos Neoplasias Bucais/induzido quimicamente Nicotina Proteínas Nucleares/genética Peroxirredoxinas/genética Lesões Pré-Cancerosas/induzido quimicamente RNA Interferente Pequeno/metabolismo Transdução de Sinais Ativação Transcricional [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Adaptor Proteins, Signal Transducing); 0 (Carcinogens); 0 (DAXX protein, human); 0 (Nuclear Proteins); 0 (RNA, Small Interfering); 6M3C89ZY6R (Nicotine); EC 1.11.1.15 (Peroxiredoxins) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180209 [Lr] Data última revisão: 180209 [Sb] Subgrupo de revista: D; IM [Da] Data de entrada para processamento: 171226 [St] Status: MEDLINE [do] DOI: 10.3760/cma.j.issn.1002-0098.2017.12.004

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[PMID]: 27777126 [Au] Autor: Luxembourg A; Kjaer SK; Nygard M; Ellison MC; Group T; Marshall JB; Radley D; Saah A [Ad] Endereço: Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: alain_luxembourg@merck.com. [Ti] Título: Design of a long-term follow-up effectiveness, immunogenicity and safety study of women who received the 9-valent human papillomavirus vaccine. [So] Source: Contemp Clin Trials;52:54-61, 2017 01. [Is] ISSN: 1559-2030 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The 9-valent human papillomavirus (HPV) (9vHPV) vaccine targets four HPV types (6/11/16/18) also covered by the quadrivalent HPV (qHPV) vaccine and five additional types (31/33/45/52/58). Vaccine efficacy to prevent HPV infection and disease was established in a Phase III clinical study in women 16-26years of age. A long-term follow-up (LTFU) study has been initiated as an extension of the Phase III clinical study to assess effectiveness of the 9vHPV vaccine up to at least 14years after the start of vaccination. It includes participants from Denmark, Norway and Sweden and uses national health registries from these countries to assess incidence of cervical pre-cancers and cancers due to the 7 oncogenic types in the vaccine (HPV 16/18/31/33/45/52/58). Incidences will be compared to the estimated incidence rate in an unvaccinated cohort of similar age and risk level. This LTFU study uses a unique design: it is an extension of a Phase III clinical study and also has elements of an epidemiological study (i.e., endpoints based on standard clinical practice; surveillance using searches from health registries); it uses a control chart method to determine whether vaccine effectiveness may be waning. Control chart methods which were developed in industrial and manufacturing settings for process and production monitoring, can be used to monitor disease incidence in real-time and promptly detect a decrease in vaccine effectiveness. Experience from this innovative study design may be applicable to other medicinal products when long-term outcomes need to be assessed, there is no control group, or outcomes are rare. [Mh] Termos MeSH primário: Neoplasia Intraepitelial Cervical/prevenção & controle Imunogenicidade da Vacina Infecções por Papillomavirus/prevenção & controle Vacinas contra Papillomavirus/uso terapêutico Lesões Pré-Cancerosas/prevenção & controle Neoplasias do Colo do Útero/prevenção & controle [Mh] Termos MeSH secundário: Adolescente Adulto Neoplasia Intraepitelial Cervical/epidemiologia Neoplasia Intraepitelial Cervical/virologia Ensaios Clínicos Fase III como Assunto Dinamarca/epidemiologia Feminino Seguimentos Seres Humanos Incidência Noruega/epidemiologia Infecções por Papillomavirus/epidemiologia Infecções por Papillomavirus/virologia Vacinas contra Papillomavirus/imunologia Lesões Pré-Cancerosas/epidemiologia Lesões Pré-Cancerosas/virologia Ensaios Clínicos Controlados Aleatórios como Assunto Suécia/epidemiologia Resultado do Tratamento Neoplasias do Colo do Útero/epidemiologia Neoplasias do Colo do Útero/virologia Neoplasias Vaginais/epidemiologia Neoplasias Vaginais/prevenção & controle Neoplasias Vaginais/virologia Neoplasias Vulvares/epidemiologia Neoplasias Vulvares/prevenção & controle Neoplasias Vulvares/virologia Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Papillomavirus Vaccines) [Em] Mês de entrada: 1712 [Cu] Atualização por classe: 180209 [Lr] Data última revisão: 180209 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161108 [St] Status: MEDLINE

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MEDLINE

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[PMID]: 29369216 [Au] Autor: Dore MP; Cipolli A; Ruggiu MW; Manca A; Bassotti G; Pes GM [Ad] Endereço: Dipartimento di Medicina Clinica e Sperimentale. [Ti] Título: Helicobacter pylori eradication may influence timing of endoscopic surveillance for gastric cancer in patients with gastric precancerous lesions: A retrospective study. [So] Source: Medicine (Baltimore);97(4):e9734, 2018 Jan. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Chronic atrophic gastritis and intestinal metaplasia related to Helicobacter pylori infection, are major risk factors for gastric adenocarcinoma. Eradication of H pylori and endoscopy surveillance of precancerous lesions may reduce the risk and/or lead to early detection of gastric cancer improving survival. In this study, the progression of precancerous lesions after H pylori treatment was evaluated.Patients with incomplete or complete intestinal metaplasia and/or gastric atrophy at the index endoscopy, were examined for the extension/histological worsening of precancerous lesions at the endoscopy surveillance for gastric cancer. Progression of lesions was evaluated according to H pylori status, age, and sex. Cox proportional hazard regression model and Kaplan-Meier curves were used to evaluate the strength of predictors for lesions progression.Among 105 patients (61 women) H pylori negative patients showed a milder worsening of gastric lesions between index and surveillance endoscopy compared with patients positive for the infection (log-rank test: P < .0001, P = .012, and P = .032 for antrum, angulus, and corpus, respectively). The Cox regression model showed persistence of H pylori infection (hazard ratio = 4.436; P < .0001) as the only relevant factor for lesion progression, whereas age >65 years and sex were not significant predictors.According to literature our results demonstrate that H pylori eradication is the major factor able to delay gastric precancerous lesions progression. Time interval for endoscopic surveillance in patients negative for H pylori infection and with gastric precancerous lesions may be extended. [Mh] Termos MeSH primário: Endoscopia do Sistema Digestório/métodos Infecções por Helicobacter/tratamento farmacológico Helicobacter pylori/efeitos dos fármacos Vigilância da População/métodos Lesões Pré-Cancerosas/diagnóstico Neoplasias Gástricas/diagnóstico [Mh] Termos MeSH secundário: Idoso Progressão da Doença Detecção Precoce de Câncer/métodos Feminino Infecções por Helicobacter/complicações Seres Humanos Intestinos/microbiologia Intestinos/patologia Masculino Metaplasia/diagnóstico Metaplasia/microbiologia Meia-Idade Lesões Pré-Cancerosas/microbiologia Modelos de Riscos Proporcionais Análise de Regressão Estudos Retrospectivos Fatores de Risco Neoplasias Gástricas/microbiologia Fatores de Tempo [Pt] Tipo de publicação: EVALUATION STUDIES; JOURNAL ARTICLE [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180208 [Lr] Data última revisão: 180208 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 180126 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000009734

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