Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
1.
J Community Health Nurs ; 41(2): 96-109, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38376116

RESUMO

PURPOSE: To prevent workplace violence (WV) against visiting nurses (VNs), understanding the influencing factors is crucial. To better comprehend potential violence prevention strategies, the U.S. Centers for Disease Control and Prevention has presented the four-level social-ecological model (SEM) at the 1) individual, 2) relationship, 3) community, and 4) societal levels. This study aims to quantify WV studies against VNs, examine the influencing factors, identify gaps based on SEM levels, and propose future research and policy directions. DESIGN: A scoping review was conducted following the five-stage protocol proposed by Arksey and O'Malley in 2005. METHODS: Systematic searches, including manual searches, were performed using English and Korean databases. Published journal articles including editorials on WV against VNs were included, irrespective of the publication date. FINDINGS: Sixty journal articles were finally selected. Until the 1990s, most of the literature comprised editorials, with empirical research emerging after the 2000s. Classifying studies by SEM level, many studies have focused on individual (86.7%) and community (66.7%) factors, but fewer have addressed relationship (21.7%) and societal (16.7%) factors. CONCLUSIONS: The study revealed that much research has focused on individual-centered training, with gaps in risk assessment tool development, training incorporating relational aspects, standardized protocols, and understanding of the impact of legal rights and policies. This article advocates a comprehensive approach that considers all SEM levels to address WV against VNs. CLINICAL EVIDENCE: The findings confirm a research gap, which suggests the direction for future research and policies. Stakeholders should be urged to implement evidence-based strategies that contribute to safer work environments for VNs.


Assuntos
Enfermeiros de Saúde Comunitária , Violência no Trabalho , Estados Unidos , Humanos , Violência no Trabalho/prevenção & controle , Local de Trabalho
2.
PLoS One ; 18(12): e0296234, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38113226

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0251243.].

3.
Public Health Nurs ; 40(6): 857-867, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37551850

RESUMO

OBJECTIVES: Although home-visit healthcare programs in Korea are expected to expand, providing hands-on experience to nursing students may be limited. This study aimed to develop and evaluate a problem-based learning (PBL) simulation module that reflects home-visit healthcare services provided by public health centers for pre-frail older adults. DESIGN AND SAMPLE: The simulation module, including PBL as prebriefing, was developed by the researchers and revised based on expert reviews. The module was evaluated using a mixed-method embedded one-group post-test-only design with focus group interviews (FGIs). Quantitative data (n = 29) were collected between April and June, 2021. FGIs (n = 10) were conducted twice in June 2021, and qualitative data were analyzed using an inductive content analysis approach. RESULTS: The average score of the Simulation Design Scale was 4.67 ± 0.36. The overall mean score of the Educational Practices Questionnaire was 4.75 ± 0.37. Three themes emerged from the FGIs: immersive learning experience, changes in perspective on nursing, and enhanced nursing competency. CONCLUSION: This PBL-based simulation module was evaluated as a systematic learning process in which nursing students could become self-directed learners, interacting and collaborating with colleagues, instructors, and environments. The module encourages them to practice home visit services.


Assuntos
Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Idoso , Aprendizagem Baseada em Problemas/métodos , Visita Domiciliar , Aprendizagem , Bacharelado em Enfermagem/métodos , Currículo
4.
Epilepsy Behav ; 140: 109112, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36780775

RESUMO

PURPOSE: This study aimed to develop a questionnaire to assess parents' treatment adherence for their child or adolescent with epilepsy (PQ-TAE). MATERIAL AND METHODS: Seventy-one preliminary items were developed as a first draft and refined based on reviews from experts and cognitive interviews with parents. Then, an online survey was conducted from June 15 to July 15, 2020, to test the psychometric properties of the questionnaire and to modify it. Reliability and validity were additionally tested using exploratory factor analysis, internal consistency, and statistical relationships including parents' partnership with healthcare providers, educational attainment, and economic status. RESULTS: The 4-factor model was adopted as the final factor structure of the PQ-TAE (CMIN/df = 2.15, RMSEA = 0.07, SRMR = 0.04, CFI = 0.93, TLI = 0.90). The reliability of the PQ-TAE was statistically acceptable (Cronbach's alpha = 0.93). The PQ-TAE score was statistically related to the partnership with healthcare providers (r = 0.58, p < 0.001), educational attainment (t = -2.12, p = 0.037), and economic status (t = -4.05, p < 0.001). CONCLUSIONS: The PQ-TAE using a 5-point Likert scale consists of 25 items classified into four factors. The higher the score (Range 25-125), the better the treatment adherence of the parent of a child or adolescent with epilepsy.


Assuntos
Epilepsia , Pais , Humanos , Criança , Adolescente , Reprodutibilidade dos Testes , Pais/psicologia , Psicometria , Cooperação e Adesão ao Tratamento , Inquéritos e Questionários , Epilepsia/tratamento farmacológico , Epilepsia/psicologia , Análise Fatorial
5.
Artigo em Inglês | MEDLINE | ID: mdl-34769828

RESUMO

Nurses working amid the COVID-19 pandemic are at increased risk of developing post-traumatic stress disorder (PTSD). This study was conducted to verify the reliability and validity of the Korean version of Impact of Event Scale-Revised (IES-R), one of the most used tools for assessing trauma. Secondary data of 249 nurses who performed face-to-face nursing tasks during the COVID-19 pandemic, collected through an online survey, were analyzed by conducting a factor analysis of the K-IES-R and testing the internal consistency and concurrent validity with the Perceived Stress Scale (PSS), Generalized Anxiety Disorder Screener (GAD-7), and Dimensions of Anger Reactions-5 (DAR-5). The result of an exploratory factor analysis of the K-IES-R supported a three-factor structure of intrusion, avoidance, and sleep disturbance, with CMIN/DF = 2.98, RMSEA = 0.09, SRMR = 0.03, CFI = 0.93, and TLI = 0.90. The Cronbach's alpha of each subscale was 0.88-0.94. The total K-IES-R score and each factor's value showed a significant correlation (moderate or higher) with the PSS, GAD-7, and DAR-5. The K-IES-R was verified as a useful tool for assessing post-traumatic stress symptoms in nurses who directly perform nursing tasks in crises such as COVID-19. This study suggests the tool be used for early assessment of post-traumatic stress symptoms in nurses and providing appropriate interventions.


Assuntos
COVID-19 , Enfermeiras e Enfermeiros , Transtornos de Estresse Pós-Traumáticos , Humanos , Pandemias , Reprodutibilidade dos Testes , República da Coreia/epidemiologia , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Inquéritos e Questionários
6.
mSphere ; 6(5): e0056421, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34523983

RESUMO

Accurate nutrient sensing is important for rapid fungal growth and exploitation of available resources. Sulfur is an important nutrient source found in a number of biological macromolecules, including proteins and lipids. The model filamentous fungus Neurospora crassa is capable of utilizing sulfur found in a variety of sources from amino acids to sulfate. During sulfur starvation, the transcription factor CYS-3 is responsible for upregulation of genes involved in sulfur uptake and assimilation. Using a combination of RNA sequencing and DNA affinity purification sequencing, we performed a global survey of the N. crassa sulfur starvation response and the role of CYS-3 in regulating sulfur-responsive genes. The CYS-3 transcription factor bound the promoters and regulated genes involved in sulfur metabolism. Additionally, CYS-3 directly activated the expression of a number of uncharacterized transporter genes, suggesting that regulation of sulfur import is an important aspect of regulation by CYS-3. CYS-3 also directly regulated the expression of genes involved in mitochondrial electron transfer. During sulfur starvation, genes involved in nitrogen metabolism, such as amino acid and nucleic acid metabolic pathways, along with genes encoding proteases and nucleases that are necessary for scavenging nitrogen, were activated. Sulfur starvation also caused changes in the expression of genes involved in carbohydrate metabolism, such as those encoding glycosyl hydrolases. Thus, our data suggest a connection between sulfur metabolism and other aspects of cellular metabolism. IMPORTANCE Identification of nutrients present in the environment is a challenge common to all organisms. Sulfur is an important nutrient source found in proteins, lipids, and electron carriers that are required for the survival of filamentous fungi such as Neurospora crassa. Here, we transcriptionally profiled the response of N. crassa to characterize the global response to sulfur starvation. We also used DNA affinity purification sequencing to identify the direct downstream targets of the transcription factor responsible for regulating genes involved in sulfur uptake and assimilation. Along with genes involved in sulfur metabolism, this transcription factor regulated a number of uncharacterized transporter genes and genes involved in mitochondrial electron transfer. Our data also suggest a connection between sulfur, nitrogen, and carbon metabolism, indicating that the regulation of a number of metabolic pathways is intertwined.


Assuntos
Proteínas Fúngicas/metabolismo , Neurospora crassa/genética , Enxofre/metabolismo , Fatores de Transcrição/metabolismo , Regulação Fúngica da Expressão Gênica , Redes Reguladoras de Genes , Redes e Vias Metabólicas/genética , Neurospora crassa/metabolismo , RNA-Seq
7.
PLoS One ; 16(5): e0251243, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33961641

RESUMO

OBJECTIVE: We assessed the prevalence of, and factors associated with, heated tobacco product (HTP) use and analysed the association between HTP use and quitting combustible cigarettes (CCs) in Korean adults. METHODS: We conducted an online survey with 7,000 adults (males, 2,300; females, 4,700; ages 20-69) out of 70,000 age-, sex- and provincial-distribution-matched individuals based on 2018 national population statistics. Females were oversampled because the prevalence of tobacco product use is very low among women in Korea. Chi-square tests were used for bivariate analyses, and odds ratios were assessed after adjusting for sociodemographic variables. RESULTS: The prevalence of current CC, electronic cigarette (EC), and HTP use was 24.8% (males, 40.4%; females, 9.3%), 6.8% (males, 10.1%; females, 3.4%), and 10.2% (males, 16.2%; females, 4.3%), respectively. Among the 574 current HTP users, 77 (13.4%) were HTP-only users and >80% were either dual users of HTP and CC/EC, or triple users of HTP, EC, and CC. Among the current CC users, the odds of having attempted to quit CCs in the past year were greater among EC-only users (aOR 2.92; 95% CI 1.81-4.69) and dual users of HTPs and ECs (aOR 8.42; 95% CI 4.85-14.62) than among non-HTP and non-EC users. Among 2,121 ever CC smokers, the likelihood of being a former CC smoker was 0.19 (95% CI 0.15-0.24) for HTP users, 0.29 (95% CI 0.20-0.42) for EC users, and 0.03 (95% CI 0.01-0.06) for users of both HTPs and ECs compared with non-HTP and non-EC users. CONCLUSION: EC-only use and dual use of HTPs and ECs were associated with increased attempts to quit CCs; however, HTP and EC use was associated with lower odds of CC smoking abstinence.


Assuntos
Abandono do Hábito de Fumar/estatística & dados numéricos , Produtos do Tabaco , Uso de Tabaco/epidemiologia , Vaping/epidemiologia , Adulto , Idoso , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia , Fumantes/estatística & dados numéricos , Adulto Jovem
8.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33753477

RESUMO

Sensing available nutrients and efficiently utilizing them is a challenge common to all organisms. The model filamentous fungus Neurospora crassa is capable of utilizing a variety of inorganic and organic nitrogen sources. Nitrogen utilization in N. crassa is regulated by a network of pathway-specific transcription factors that activate genes necessary to utilize specific nitrogen sources in combination with nitrogen catabolite repression regulatory proteins. We identified an uncharacterized pathway-specific transcription factor, amn-1, that is required for utilization of the nonpreferred nitrogen sources proline, branched-chain amino acids, and aromatic amino acids. AMN-1 also plays a role in regulating genes involved in responding to the simple sugar mannose, suggesting an integration of nitrogen and carbon metabolism. The utilization of nonpreferred nitrogen sources, which require metabolic processing before being used as a nitrogen source, is also regulated by the nitrogen catabolite regulator NIT-2. Using RNA sequencing combined with DNA affinity purification sequencing, we performed a survey of the role of NIT-2 and the pathway-specific transcription factors NIT-4 and AMN-1 in directly regulating genes involved in nitrogen utilization. Although previous studies suggested promoter binding by both a pathway-specific transcription factor and NIT-2 may be necessary for activation of nitrogen-responsive genes, our data show that pathway-specific transcription factors regulate genes involved in the catabolism of specific nitrogen sources, while NIT-2 regulates genes involved in utilization of all nonpreferred nitrogen sources, such as nitrogen transporters. Together, these transcription factors form a nutrient sensing network that allows N. crassa cells to regulate nitrogen utilization.


Assuntos
Repressão Catabólica/genética , Regulação Fúngica da Expressão Gênica , Neurospora crassa/fisiologia , Nitrogênio/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Fúngicas/metabolismo , Redes Reguladoras de Genes , Redes e Vias Metabólicas/genética , RNA-Seq , Transativadores , Fatores de Transcrição/metabolismo
10.
Sci Rep ; 10(1): 5250, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251355

RESUMO

Fungal plant pathogens remain a serious threat to the sustainable agriculture and forestry, despite the extensive efforts undertaken to control their spread. White root rot disease is threatening rubber tree (Hevea brasiliensis) plantations throughout South and Southeast Asia and Western Africa, causing tree mortality and severe yield losses. Here, we report the complete genome sequence of the basidiomycete fungus Rigidoporus microporus, a causative agent of the disease. Our phylogenetic analysis confirmed the position of R. microporus among the members of Hymenochaetales, an understudied group of basidiomycetes. Our analysis further identified pathogen's genes with a predicted role in the decay of plant cell wall polymers, in the utilization of latex components and in interspecific interactions between the pathogen and other fungi. We also detected putative horizontal gene transfer events in the genome of R. microporus. The reported first genome sequence of a tropical rubber tree pathogen R. microporus should contribute to the better understanding of how the fungus is able to facilitate wood decay and nutrient cycling as well as tolerate latex and utilize resinous extractives.


Assuntos
Proteínas Fúngicas/genética , Látex/metabolismo , Polyporales/genética , Polyporales/patogenicidade , Madeira/microbiologia , Parede Celular/metabolismo , Parede Celular/microbiologia , Enzimas/genética , Enzimas/metabolismo , Regulação Fúngica da Expressão Gênica , Transferência Genética Horizontal , Genoma Fúngico , Interações Hospedeiro-Patógeno/genética , Interações Microbianas/genética , Filogenia , Polyporales/metabolismo , Metabolismo Secundário , Madeira/metabolismo
11.
Proc Natl Acad Sci U S A ; 117(11): 6003-6013, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32111691

RESUMO

Filamentous fungi, such as Neurospora crassa, are very efficient in deconstructing plant biomass by the secretion of an arsenal of plant cell wall-degrading enzymes, by remodeling metabolism to accommodate production of secreted enzymes, and by enabling transport and intracellular utilization of plant biomass components. Although a number of enzymes and transcriptional regulators involved in plant biomass utilization have been identified, how filamentous fungi sense and integrate nutritional information encoded in the plant cell wall into a regulatory hierarchy for optimal utilization of complex carbon sources is not understood. Here, we performed transcriptional profiling of N. crassa on 40 different carbon sources, including plant biomass, to provide data on how fungi sense simple to complex carbohydrates. From these data, we identified regulatory factors in N. crassa and characterized one (PDR-2) associated with pectin utilization and one with pectin/hemicellulose utilization (ARA-1). Using in vitro DNA affinity purification sequencing (DAP-seq), we identified direct targets of transcription factors involved in regulating genes encoding plant cell wall-degrading enzymes. In particular, our data clarified the role of the transcription factor VIB-1 in the regulation of genes encoding plant cell wall-degrading enzymes and nutrient scavenging and revealed a major role of the carbon catabolite repressor CRE-1 in regulating the expression of major facilitator transporter genes. These data contribute to a more complete understanding of cross talk between transcription factors and their target genes, which are involved in regulating nutrient sensing and plant biomass utilization on a global level.


Assuntos
Parede Celular/metabolismo , Proteínas Fúngicas/metabolismo , Neurospora crassa/genética , Pectinas/metabolismo , Polissacarídeos/metabolismo , Fatores de Transcrição/metabolismo , Biocombustíveis , Biomassa , Repressão Catabólica , Parede Celular/química , Regulação Fúngica da Expressão Gênica , Engenharia Metabólica/métodos , Redes e Vias Metabólicas/genética , Neurospora crassa/metabolismo , RNA-Seq
12.
Sci Data ; 6(1): 285, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772173

RESUMO

Metagenomic sequence data from defined mock communities is crucial for the assessment of sequencing platform performance and downstream analyses, including assembly, binning and taxonomic assignment. We report a comparison of shotgun metagenome sequencing and assembly metrics of a defined microbial mock community using the Oxford Nanopore Technologies (ONT) MinION, PacBio and Illumina sequencing platforms. Our synthetic microbial community BMock12 consists of 12 bacterial strains with genome sizes spanning 3.2-7.2 Mbp, 40-73% GC content, and 1.5-7.3% repeats. Size selection of both PacBio and ONT sequencing libraries prior to sequencing was essential to yield comparable relative abundances of organisms among all sequencing technologies. While the Illumina-based metagenome assembly yielded good coverage with few misassemblies, contiguity was greatly improved by both, Illumina + ONT and Illumina + PacBio hybrid assemblies but increased misassemblies, most notably in genomes with high sequence similarity to each other. Our resulting datasets allow evaluation and benchmarking of bioinformatics software on Illumina, PacBio and ONT platforms in parallel.


Assuntos
Metagenoma , Microbiota , Análise de Sequência de DNA/métodos , Bactérias/classificação , Sequenciamento de Nucleotídeos em Larga Escala
13.
Mol Biol Evol ; 35(8): 1840-1854, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29771364

RESUMO

Ustilaginomycotina is home to a broad array of fungi including important plant pathogens collectively called smut fungi. Smuts are biotrophs that produce characteristic perennating propagules called teliospores, one of which, Ustilago maydis, is a model genetic organism. Broad exploration of smut biology has been hampered by limited phylogenetic resolution of Ustilaginiomycotina as well as an overall lack of genomic data for members of this subphylum. In this study, we sequenced eight Ustilaginomycotina genomes from previously unrepresented lineages, deciphered ordinal-level phylogenetic relationships for the subphylum, and performed comparative analyses. Unlike other Basidiomycota subphyla, all sampled Ustilaginomycotina genomes are relatively small and compact. Ancestral state reconstruction analyses indicate that teliospore formation was present at the origin of the subphylum. Divergence time estimation dates the divergence of most extant smut fungi after that of grasses (Poaceae). However, we found limited conservation of well-characterized genes related to smut pathogenesis from U. maydis, indicating dissimilar pathogenic mechanisms exist across other smut lineages. The genomes of Malasseziomycetes are highly diverged from the other sampled Ustilaginomycotina, likely due to their unique history as mammal-associated lipophilic yeasts. Despite extensive genomic data, the phylogenetic placement of this class remains ambiguous. Although the sampled Ustilaginomycotina members lack many core enzymes for plant cell wall decomposition and starch catabolism, we identified several novel carbohydrate active enzymes potentially related to pectin breakdown. Finally, ∼50% of Ustilaginomycotina species-specific genes are present in previously undersampled and rare lineages, highlighting the importance of exploring fungal diversity as a resource for novel gene discovery.


Assuntos
Interações Hospedeiro-Patógeno/genética , Filogenia , Ustilaginales/genética , Genoma Fúngico , Doenças das Plantas , Ustilaginales/classificação , Ustilaginales/enzimologia , Ustilaginales/patogenicidade , Sequenciamento Completo do Genoma
15.
Nat Ecol Evol ; 1(12): 1931-1941, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29085064

RESUMO

Armillaria species are both devastating forest pathogens and some of the largest terrestrial organisms on Earth. They forage for hosts and achieve immense colony sizes via rhizomorphs, root-like multicellular structures of clonal dispersal. Here, we sequenced and analysed the genomes of four Armillaria species and performed RNA sequencing and quantitative proteomic analysis on the invasive and reproductive developmental stages of A. ostoyae. Comparison with 22 related fungi revealed a significant genome expansion in Armillaria, affecting several pathogenicity-related genes, lignocellulose-degrading enzymes and lineage-specific genes expressed during rhizomorph development. Rhizomorphs express an evolutionarily young transcriptome that shares features with the transcriptomes of both fruiting bodies and vegetative mycelia. Several genes show concomitant upregulation in rhizomorphs and fruiting bodies and share cis-regulatory signatures in their promoters, providing genetic and regulatory insights into complex multicellularity in fungi. Our results suggest that the evolution of the unique dispersal and pathogenicity mechanisms of Armillaria might have drawn upon ancestral genetic toolkits for wood-decay, morphogenesis and complex multicellularity.


Assuntos
Armillaria/genética , Proteínas Fúngicas/genética , Genoma Fúngico , Proteômica , Análise de Sequência de RNA , Especificidade da Espécie , Transcriptoma
16.
J Korean Acad Nurs ; 47(4): 499-513, 2017 Aug.
Artigo em Coreano | MEDLINE | ID: mdl-28894072

RESUMO

PURPOSE: This concept analysis was done to clarify 'uncertainty in epilepsy'. METHODS: Walker and Avant's methodology guided the analysis. In addition, the concept was compared with uncertainty in other health problems. RESULTS: 'Uncertainty in epilepsy' was defined as being in the condition as seen from the epilepsy experience where cues were difficult to understand because they changed, were in discord with past ones, or they had two or more contradictory values at the same time. Uncertainty in epilepsy is evolved from appraisal of the epilepsy experience. As a result, uncertainty leads epilepsy patients, their family or health care providers to impaired functioning and proactive/passive coping behavior. CONCLUSION: Epilepsy patients with uncertainty need to be supported by nursing strategies for proactive, rational coping behavior. This achievement has implications for interventions aimed at changing perception of epilepsy patients, their families or health care providers who must deal with uncertainty.


Assuntos
Epilepsia/psicologia , Adaptação Psicológica , Bases de Dados Factuais , Epilepsia/patologia , Humanos , Índice de Gravidade de Doença , Incerteza
17.
Oncoscience ; 2(4): 410-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26097874

RESUMO

S100A2, a member of the S100 protein family, is known to be downregulated in a number of human cancers, leading to its designation as a potential tumor suppressor gene. Here, we investigated the expression and methylation status of S100A2 in head&neck and bladder cancer. Reduced mRNA and protein expression was observed in 8 head&neck and bladder cancer cell lines. To explore the mechanism responsible for the downregulation of S100A2, we treated six cell lines with 5-aza-2'-deoxycytidine. We found S100A2 is silenced in association with aberrant promoter-region methylation and its expression is restored with 5-aza-2'-deoxycytidine treatment. Of 31 primary head&neck cancer cases and 31 bladder cancer cases, promoter methylation was detected in 90% and 80% of cases, respectively. Interestingly, only 1/9 of normal head&neck tissues and 2/6 of normal bladder tissues showed promoter methylation. S100A2 promoter methylation can be detected in urine and is more frequent in bladder cancer patients than in healthy subjects (96% vs 48% respectively). Moreover, increased methylation of S100A2 is linked to the progression of the tumor in bladder cancer (p<0.01). Together, this data shows that methylation-associated inactivation of S100A2 is frequent and may be an important event in the tumorigenesis of head&neck and bladder cancer.

18.
PLoS One ; 7(9): e44951, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23028699

RESUMO

The human cysteine dioxygenase 1 (CDO1) gene is a non-heme structured, iron-containing metalloenzyme involved in the conversion of cysteine to cysteine sulfinate, and plays a key role in taurine biosynthesis. In our search for novel methylated gene promoters, we have analyzed differential RNA expression profiles of colorectal cancer (CRC) cell lines with or without treatment of 5-aza-2'-deoxycytidine. Among the genes identified, the CDO1 promoter was found to be differentially methylated in primary CRC tissues with high frequency compared to normal colon tissues. In addition, a statistically significant difference in the frequency of CDO1 promoter methylation was observed between primary normal and tumor tissues derived from breast, esophagus, lung, bladder and stomach. Downregulation of CDO1 mRNA and protein levels were observed in cancer cell lines and tumors derived from these tissue types. Expression of CDO1 was tightly controlled by promoter methylation, suggesting that promoter methylation and silencing of CDO1 may be a common event in human carcinogenesis. Moreover, forced expression of full-length CDO1 in human cancer cells markedly decreased the tumor cell growth in an in vitro cell culture and/or an in vivo mouse model, whereas knockdown of CDO1 increased cell growth in culture. Our data implicate CDO1 as a novel tumor suppressor gene and a potentially valuable molecular marker for human cancer.


Assuntos
Cisteína Dioxigenase/genética , Inativação Gênica , Genes Supressores de Tumor , Neoplasias/genética , Regiões Promotoras Genéticas/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisteína Dioxigenase/deficiência , Metilação de DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Epigênese Genética/efeitos dos fármacos , Epigênese Genética/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Neoplasias/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Regiões Promotoras Genéticas/efeitos dos fármacos
19.
Exp Biol Med (Maywood) ; 236(4): 375-89, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21427235

RESUMO

As with many cancers, early detection of head and neck cancer increases a patient's survival rate. If diagnosed early, its five-year survival nears 90% with standard therapy alone. Unfortunately, the average survival rate for head and neck cancer is low due to the difficulty in early detection and achieving a sustainable response. Conventional treatments are not adequate for the majority of advanced or recurrent head and neck cancer patients because of the remarkable resistance of tumors to chemotherapy and radiation, and the situation is especially devastating for the first time treatment failure. The major limitations of these treatments are the lack of specificity for the tumor cell and unacceptable toxicity to the patient. As a result, current research in therapeutics for advanced, chemotherapy-resistant or recurrent head and neck cancer patients has focused on new treatment modalities that exploit biological differences between tumor and normal cells. These therapies include monoclonal antibodies, molecular inhibitors, gene therapy and photodynamic therapy. This article reviews the current preclinical and clinical evidence of these experimental therapeutics as they relate to head and neck cancer.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Anticorpos Monoclonais/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Terapia Genética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Humanos , Fotoquimioterapia
20.
Int J Cancer ; 128(10): 2261-73, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-20658532

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the sixth most frequent cause of cancer death in the world, and cigarette smoke is a key factor in esophageal carcinogenesis. To identify molecular changes during cigarette smoke-induced ESCC, we examined the methylation status of 13 gene promoters in the human immortalized, nontumorigenic esophageal epithelial cell line (Het-1A) that were exposed to mainstream (MSE) or sidestream cigarette smoke extract (SSE) for 6 months in culture. The promoter of sequence-specific single-stranded DNA-binding protein 2 (SSBP2) was methylated in the Het-1A cells exposed to MSE (MSE-Het-1A). Promoter methylation (86%, 56/70) and downregulation of SSBP2 expression were frequently detected in tumor tissues from ESCC patients. In addition, reintroduction of SSBP2 in an ESCC cell line (TE1) that does not express SSBP2 and in the MSE-Het-1A cells inhibited expression of LRP6 and Dvl3, which are mediators of the Wnt signaling pathway. SSBP2 expression markedly decreased the colony-forming ability of ESCC cell lines and significantly inhibited cell growth of the MSE-Het-1A cells. Our results indicate that cigarette smoking is a cause of SSBP2 promoter methylation and that SSBP2 harbors a tumor suppressive role in ESCC through inhibition of the Wnt signaling pathway.


Assuntos
Carcinoma de Células Escamosas/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Neoplasias Esofágicas/genética , Nicotiana , Regiões Promotoras Genéticas , Fumaça , Linhagem Celular Transformada , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase Via Transcriptase Reversa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...