Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
Mais filtros

Bases de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
J Clin Nurs ; 29(21-22): 4313-4320, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32865257

RESUMO

AIMS AND OBJECTIVES: To compare two health literacy measurements' ability to assess older adults' medication adherence by using the Korean Health Literacy Screening Questions (KHLSQ) and the Modified Korean Functional Health Literacy Test (M-KFHLT), and to identify an appropriate health literacy measurement. BACKGROUND: Lower health literacy has been associated with poorer medication adherence. Thus, health professionals should evaluate the available health literacy assessment instruments they are using and choose an appropriate instrument to assess health literacy to increase older adults' medication adherence. DESIGN: Following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist, a descriptive, cross-sectional study was conducted. METHODS: From November 2017-May 2018, 116 community-dwelling older adults were recruited in South Korea. Questionnaires were completed during a face-to-face interview with each participant in a private room; health literacy was assessed using the KHLSQ and the M-KFHLT and medication adherence using the Morisky Medication Adherence Scale. RESULTS: Health literacy assessed using the KHLSQ was found to be a predictor of medication adherence, but was not a predictor when measured by the M-KFHLT. Having low income, multiple chronic diseases and vision problems were also significant factors related to medication adherence. CONCLUSIONS: This study suggests that health literacy was negatively associated with medication adherence. Furthermore, KHLSQ is an appropriate tool for healthcare providers to use when assessing health literacy to predict older adults' medication adherence. RELEVANCE TO CLINICAL PRACTICE: This finding indicated that healthcare providers should select an appropriate health literacy measurement that suits their purposes and the population they serve, particularly for older adults.


Assuntos
Letramento em Saúde , Adesão à Medicação , Idoso , Estudos Transversais , Humanos , República da Coreia , Inquéritos e Questionários
2.
Biochem J ; 474(10): 1603-1618, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28473628

RESUMO

The enzyme Dicer is best known for its role as a riboendonuclease in the small RNA pathway. In this canonical role, Dicer is a critical regulator of the biogenesis of microRNA and small interfering RNA, as well as a growing number of additional small RNAs derived from various sources. Emerging evidence demonstrates that Dicer's endonuclease role extends beyond the generation of small RNAs; it is also involved in processing additional endogenous and exogenous substrates, and is becoming increasingly implicated in regulating a variety of other cellular processes, outside of its endonuclease function. This review will describe the canonical and newly identified functions of Dicer.


Assuntos
RNA Helicases DEAD-box/metabolismo , Regulação da Expressão Gênica , Modelos Moleculares , Interferência de RNA , Estabilidade de RNA , RNA Citoplasmático Pequeno/metabolismo , RNA Nucleolar Pequeno/metabolismo , Ribonuclease III/metabolismo , Animais , Apoptose , RNA Helicases DEAD-box/química , RNA Helicases DEAD-box/genética , Exossomos/enzimologia , Exossomos/metabolismo , Interações Hospedeiro-Patógeno , Humanos , MicroRNAs/metabolismo , Filogenia , Domínios e Motivos de Interação entre Proteínas , RNA Interferente Pequeno/metabolismo , RNA de Transferência/metabolismo , RNA Viral/metabolismo , Ribonuclease III/química , Ribonuclease III/genética , Especificidade por Substrato , Repetições de Trinucleotídeos
3.
Nurs Health Sci ; 16(3): 352-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24372859

RESUMO

The study aims to investigate the effects of education in an obesity-control program (EOCP) on the percentage of body fat and flexibility in obese women in Korea. Women with over 30% body fat were offered EOCP between July 2012 and October 2012. The EOCP consisted of an educational program, exercise program, and counseling. The numbers of participants both in the EOCP and control group were 17. The study was analyzed by Wilcoxon signed-rank test using the Statistical Analysis System package. The EOCP participants presented statistically significant increases in the degree of forward trunk flexion, but only the percentage of the body fat showed differences within the EOCP group. The EOCP improved flexibility in obese women, and can be used in local obesity-control programs.


Assuntos
Tecido Adiposo/fisiologia , Terapia por Exercício/métodos , Zeladoria , Obesidade/prevenção & controle , Amplitude de Movimento Articular/fisiologia , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Aconselhamento/métodos , Feminino , Promoção da Saúde/métodos , Humanos , Pessoa de Meia-Idade , Pesquisa em Avaliação de Enfermagem , Obesidade/enfermagem , Avaliação de Processos e Resultados em Cuidados de Saúde , Educação de Pacientes como Assunto , Avaliação de Programas e Projetos de Saúde , Seul , Estatísticas não Paramétricas , Fatores de Tempo , Saúde da Mulher
4.
Healthcare (Basel) ; 12(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38338186

RESUMO

BACKGROUND: In the post-COVID-19 condition, infection control education is important for geriatric care workers who care for the elderly and are vulnerable to emerging infectious diseases. This study was conducted to enhance the insight into the experiences of geriatric care workers in managing novel infectious diseases (COVID-19) and to identify the newly required educational requirements necessary to effectively implement infectious disease control. METHODS: This is a qualitative and pilot study using focus group interviews. Data from 10 participants were collected using a focus group interview. The data were analyzed using Qualitative content analysis. RESULTS: The findings showed that geriatric healthcare workers experienced difficulties following infection control protocols and emotional distress related to visitor restrictions and had an increased workload. The participants requested further education regarding general knowledge of infectious diseases to decrease their fears of infection and reported that visual and practical teaching methods were preferable. CONCLUSIONS: Further attention is needed regarding the education of infection control to strengthen infection prevention in long-term care facilities vulnerable to the spread of emerging infectious diseases.

5.
Nucleic Acids Res ; 39(4): 1510-25, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20972213

RESUMO

RNA interference is a powerful mechanism for sequence-specific inhibition of gene expression. It is widely known that small interfering RNAs (siRNAs) targeting the same region of a target-messenger RNA can have widely different efficacies. In efforts to better understand the siRNA features that influence knockdown efficiency, we analyzed siRNA interactions with a high-molecular weight complex in whole cell extracts prepared from two different cell lines. Using biochemical tools to study the nature of the complex, our results demonstrate that the primary siRNA-binding protein in the whole cell extracts is Dicer. We find that Dicer is capable of discriminating highly functional versus poorly functional siRNAs by recognizing the presence of 2-nt 3' overhangs and the thermodynamic properties of 2-4 bp on both ends of effective siRNAs. Our results suggest a role for Dicer in pre-selection of effective siRNAs for handoff to Ago2. This initial selection is reflective of the overall silencing potential of an siRNA.


Assuntos
Interferência de RNA , RNA Interferente Pequeno/metabolismo , Complexo de Inativação Induzido por RNA/metabolismo , Ribonuclease III/fisiologia , Proteínas Argonautas , Extratos Celulares , Fator de Iniciação 2 em Eucariotos/fisiologia , Células HCT116 , Células HEK293 , Humanos , RNA Interferente Pequeno/química , Proteínas de Ligação a RNA/fisiologia
6.
Ann Geriatr Med Res ; 27(1): 22-31, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37013435

RESUMO

BACKGROUND: This study developed a preliminary instrument to measure nurses' infection prevention compliance against emerging respiratory infectious diseases and to verify the reliability and validity of the developed instrument. METHOD: The participants were 199 nurses working at a university hospital with more than 800 beds and two long-term care hospitals. Data were collected in May 2022. RESULTS: The final version of the developed instrument consisted of six factors and 34 items, with an explanatory power of 61.68%. The six factors were equipment and environment management and education, hand hygiene and respiratory etiquette, infection risk assessment and flow management, protection of employees in contact with infected patients, ward access management of patients with infectious diseases, and wearing and removing personal protective equipment. We verified the convergent and discriminant validities of these factors. The instrument's internal consistency was adequate (Cronbach's α=0.82), and the Cronbach's α of each factor ranged from 0.71 to 0.91. CONCLUSION: This instrument can be utilized to determine the level of nurses' compliance with infection prevention activity against emerging respiratory infectious diseases and will contribute to measuring the effectiveness of future programs promoting infection-preventive activities.

7.
West J Nurs Res ; 45(6): 554-561, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36715305

RESUMO

Frontline screening nurses experienced exhaustion and depressive symptoms as a long-term impact of COVID-19. This study aimed to explore fatigue, depression, and empowerment among frontline screening nurses and examine the factors influencing depression. This was a descriptive cross-sectional study. The study included 140 frontline screening nurses in South Korea recruited from February to March 2021. The measures included a fatigue scale, the Text of Items Measuring Empowerment (TIME), and the Center for Epidemiological Studies Depression Scale (CES-D). The STROBE checklist was used for reporting aspects of the cross-sectional design. Frontline screening nurses showed high fatigue scores (M = 3.47, SD = 0.55), and 55.7% (n = 78) of them were depressed and had low empowerment scores (M = 3.53, SD = 0.69). Empowerment and fatigue were predictors of depression. Increased empowerment and decreased fatigue were important in decreasing depression. Therefore, efforts to provide sufficient staffing, screening for depression, and listening to nurses' voices are necessary.


Assuntos
COVID-19 , Enfermeiras e Enfermeiros , Humanos , Estudos Transversais , Depressão/diagnóstico , Fadiga/diagnóstico , Fadiga/etiologia , Inquéritos e Questionários
8.
Methods Mol Biol ; 2666: 317-346, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37166674

RESUMO

Live cell-based SELEX (Systematic Evolution of Ligand EXponential enrichment) is a promising approach for identifying aptamers that can selectively bind to a cell-surface receptor or recognize a particular target cell population. In particular, it offers a facile selection strategy for some special cell-surface proteins that are originally glycosylated or heavily posttranslationally modified and are unavailable in their native/active conformation after in vitro expression and purification. In this chapter, we describe a generalized procedure for evolution of cell type-specific RNA aptamers targeting a cell membrane bound target by combining the live cell-based SELEX strategy with high-throughput sequencing (HTS) and bioinformatics analysis.


Assuntos
Aptâmeros de Nucleotídeos , Aptâmeros de Nucleotídeos/genética , Aptâmeros de Nucleotídeos/metabolismo , Técnica de Seleção de Aptâmeros/métodos , Biologia Computacional , Ligantes , Sequenciamento de Nucleotídeos em Larga Escala/métodos
9.
Small ; 8(2): 209-13, 2012 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-22081508

RESUMO

A method in which a permanent magnet is introduced onto polydiacetylene (PDA) vesicle chips is introduced for enhancement of the fluorescence of PDA vesicles. This strategy can be applied to general antibody-based PDA vesicle chips to detect clinically important biomarkers for disease diagnosis.


Assuntos
Técnicas Biossensoriais/métodos , Polímeros , Poli-Inos , Neoplasias da Próstata/diagnóstico , Anticorpos Imobilizados , Anticorpos Monoclonais , Técnicas Biossensoriais/estatística & dados numéricos , Biotina , Fluorescência , Humanos , Fenômenos Magnéticos , Masculino , Microscopia Eletrônica de Varredura , Polímero Poliacetilênico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Estreptavidina , alfa 1-Antiquimotripsina/sangue , alfa-Macroglobulinas/análise
10.
Genes (Basel) ; 13(3)2022 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-35327991

RESUMO

Small interfering RNAs (siRNAs) are artificial molecules used to silence genes of interest through the RNA interference (RNAi) pathway, mediated by the endoribonuclease Dicer. Dicer-substrate small interfering RNAs (DsiRNAs) are an alternative to conventional 21-mer siRNAs, with an increased effectiveness of up to 100-fold compared to traditional 21-mer designs. DsiRNAs have a novel asymmetric design that allows them to be processed by Dicer into the desired conventional siRNAs. DsiRNAs are a useful tool for sequence-specific gene silencing, but the molecular mechanism underlying their increased efficacy is not precisely understood. In this study, to gain a deeper understanding of Dicer function in DsiRNAs, we designed nicked DsiRNAs with and without tetra-loops to target a specific mRNA sequence, established a Dicer knockout in the HCT116 cell line, and analyzed the efficacy of various DsiRNAs on RNAi-mediated gene silencing activity. The gene silencing activity of all DsiRNAs was reduced in Dicer knockout cells. We demonstrated that tetra-looped DsiRNAs exhibited increased efficacy for gene silencing, which was mediated by Dicer protein. Thus, this study improves our understanding of Dicer function, a key component of RNAi silencing, which will inform RNAi research and applications.


Assuntos
Inativação Gênica , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo
11.
Children (Basel) ; 8(9)2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34572255

RESUMO

The Rect-spring appliance, used for the management of ectopically erupting molars, shows weak retention on mesially tilted molars. We present three modifications of the appliance for better engagement and their advantages. We describe cases of two 7-year-old patients with ectopically erupting maxillary first molars with a 2.2 mm and 2.5 mm depth of entrapment, respectively. The modified Rect-spring (mRS) was inserted between the ectopically erupting first molar and adjacent primary second molar, and exerted a distalization force with an interproximal wedging effect at the same time. After 3 months, the ectopically erupting first molars were successfully brought into proper occlusion. No discomfort was reported. The mRS is suitable for various locking cases except for severely tilted molars without requiring any laboratory procedures. We suggest it as the first choice for unlocking the first molars.

12.
Analyst ; 134(9): 1896-901, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19684916

RESUMO

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of a newly emerged disease SARS. The SARS-CoV nucleocapsid (N) protein is one of the most abundant structural proteins and serves as a diagnostic marker for accurate and sensitive detection of the virus. Using a SELEX (systematic evolution of ligand by exponential enrichment) procedure and recombinant N protein, we selected a high-affinity RNA aptamer capable of binding to N protein with a dissociation constant of 1.65 nM. Electrophoretic mobility shift assays and RNA competition experiments showed that the selected aptamer recognized selectively the C-terminal region of N protein with high specificity. Using a chemiluminescence immunosorbent assay and a nanoarray aptamer chip with the selected aptamer as an antigen-capturing agent, we could sensitively detect N protein at a concentration as low as 2 pg/ml. These aptamer-antibody hybrid immunoassays may be useful for rapid, sensitive detection of SARS-CoV N protein.


Assuntos
Aptâmeros de Nucleotídeos , Imunoensaio/métodos , Proteínas do Nucleocapsídeo/análise , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Animais , Chlorocebus aethiops , Proteínas do Nucleocapsídeo de Coronavírus , Medições Luminescentes , Análise em Microsséries , Células Vero
13.
Clin Cancer Res ; 14(1): 281-90, 2008 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-18172280

RESUMO

PURPOSE: Our previous studies suggested that human telomerase reverse transcriptase (hTERT) RNA-targeting trans-splicing ribozyme could be a useful tool for cancer gene therapy. Here, we investigated whether adenoviruses harboring this ribozyme can be systemically delivered to mice, and whether they selectively mark tumors expressing hTERT and sensitize them to ganciclovir treatments. EXPERIMENTAL DESIGN: We constructed adenoviral vectors containing modified hTERT-targeting trans-splicing ribozyme with downstream reporter gene (Ad-Ribo-LacZ) or suicide gene (Ad-Ribo-HSVtk) driven by a cytomegalovirus promoter. The tumor-specific trans-splicing reaction and the tumor-killing effect of adenoviruses harboring ribozyme were investigated both in vitro and in vivo using mice with intrahepatic colon cancer metastasis via systemic administration. The safety of systemic administration of the viruses was also evaluated. RESULTS: We showed that Ad-Ribo-LacZ, when injected i.v., performs a highly specific trans-splicing reaction on hTERT mRNA and that it selectively marks tumors expressing hTERT in mice. More importantly, i.v. injection of Ad-Ribo-HSVtk plus ganciclovir significantly reduced tumor burden, with minimal liver toxicity, in mice with metastatic liver cancer, compared with the untreated group (P = 0.0009). Moreover, animals receiving Ad-Ribo-HSVtk showed improved survival compared with controls (P < 0.0001). CONCLUSIONS: This study shows that systemically delivered adenovirus harboring trans-splicing ribozyme can recognize cancer-specific transcripts and reprogram them to combat the cancer cells. Use of trans-splicing ribozymes seems to be a potentially useful gene therapy for cancer.


Assuntos
Neoplasias do Colo/patologia , Terapia Genética/métodos , Neoplasias Hepáticas/terapia , RNA Catalítico/genética , Trans-Splicing , Adenoviridae/genética , Animais , Sequência de Bases , Modelos Animais de Doenças , Feminino , Genes Reporter , Vetores Genéticos , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/secundário , Camundongos , Camundongos Nus , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Telomerase/genética , Telomerase/metabolismo
14.
J Microbiol Biotechnol ; 19(9): 1070-6, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19809268

RESUMO

Telomerase reverse transcriptase (TERT), which prolongs the replicative life span of cells, is highly upregulated in 85-90% of human cancers, whereas most normal somatic tissues in humans express limited levels of the telomerase activity. Therefore, TERT has been a potential target for anticancer therapy. Recently, we described a new approach to human cancer gene therapy, which is based on the group I intron of Tetrahymena thermophila. This ribozyme can specifically mediate RNA replacement of human TERT (hTERT) transcript with a new transcript harboring anticancer activity through a trans-splicing reaction, resulting in selective regression of hTERT-positive cancer cells. However, to validate the therapeutic potential of the ribozyme in animal models, ribozymes targeting inherent transcripts of the animal should be developed. In this study, we developed a Tetrahymena-based trans-splicing ribozyme that can specifically target and replace the mouse TERT (mTERT) RNA. This ribozyme can trigger transgene activity not only also in mTERT-expressing cells but hTERT-positive cancer cells. Importantly, the ribozyme could selectively induce activity of the suicide gene, a herpes simplex virus thymidine kinase gene, in cancer cells expressing the TERT RNA and thereby specifically hamper the survival of these cells when treated with ganciclovir. The mTERT-targeting ribozyme will be useful for evaluation of the RNA replacement approach as a cancer gene therapeutic tool in the mouse model with syngeneic tumors.


Assuntos
Íntrons/genética , Telomerase/genética , Telomerase/uso terapêutico , Tetrahymena thermophila/genética , Células 3T3 , Animais , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Éxons/genética , Fibroblastos/citologia , Fibroblastos/fisiologia , Genes Transgênicos Suicidas/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Pulmão/embriologia , Camundongos , Tetrahymena thermophila/enzimologia
15.
Appl Nurs Res ; 22(1): 42-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19171294

RESUMO

This study investigated the effects of a diabetes outpatient intensive management program (DOIMP) on glycosylated hemoglobin (HbA(1)c) levels and adherence to diabetes control recommendations over a 12-week follow-up period for patients with diabetes. The DOIMP was composed of multidisciplinary diabetes education, complication monitoring, and telephone counseling. Twenty-five patients in the intervention group participated in the DOIMP, whereas 24 in the control group were briefed on the conventional description of diabetes mellitus by diabetes education nurses. Patients in the intervention group decreased their mean HbA(1)c levels by 2.3%, as compared with 0.4% in the control group. There was a significant increase in adherence to diet for the intervention group as compared with the control group. These findings indicate that the DOIMP can improve HbA(1)c levels and adherence to diet in patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Hemoglobinas Glicadas/análise , Cooperação do Paciente , Adulto , Aconselhamento , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto
16.
Appl Nurs Res ; 21(2): 84-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18457747

RESUMO

This study applied a 6-month educational intervention that used the technology of the short message service (via cellular phones) and the Internet for obese patients with type 2 diabetes. Eighteen patients were randomly assigned to an intervention group and 16 were assigned to a control group (N = 34). Patients in the intervention group were asked to access a web site by using personal cellular phones or computer Internet services to input their blood glucose levels daily. Participants were then sent optimal recommendations via cellular phone and the Internet weekly. After 6 months, the intervention group had a statistically significant decrease in glycosylated hemoglobin, fasting plasma glucose, 2-hour postmeal glucose, and total cholesterol, as compared with the control group.


Assuntos
Telefone Celular , Diabetes Mellitus Tipo 2/prevenção & controle , Internet , Obesidade/enfermagem , Educação de Pacientes como Assunto/métodos , Feminino , Hemoglobina E/análogos & derivados , Hemoglobina E/metabolismo , Humanos , Hiperlipidemias/prevenção & controle , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade
17.
Oligonucleotides ; 17(1): 95-103, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17461766

RESUMO

Cytoskeleton-associated protein 2 (CKAP2) is known to be highly expressed in primary human cancers as well as most cancer cell lines. CKAP2 functions as microtubule stabilizer and probably as cell proliferation inducer, indicating that CKAP2 might be a potential anticancer target. In this study, we developed a specific ribozyme that can replace mouse CKAP2 (mCKAP2) RNA with new transcripts through trans-splicing reaction. This specific RNA replacement resulted in triggering of transgene activity selectively in mammalian cells that express the mCKAP2 RNA. Simultaneously, the ribozyme reduced the expression level of the target RNA in the cells. Noticeably, the ribozyme selectively induced activity of the suicide gene herpes simplex virus thymidine kinase in cells expressing the mCKAP2 RNA and thereby specifically retarded the survival of these cells with ganciclovir treatment. This mCKAP2-specific ribozyme will be useful for validation of the RNA replacement as cancer gene therapy approach in mouse model with syngeneic tumors.


Assuntos
Proteínas do Citoesqueleto/genética , RNA Catalítico/metabolismo , RNA Mensageiro/metabolismo , Trans-Splicing , Animais , Células Cultivadas , Terapia Genética , Humanos , Camundongos , RNA Catalítico/genética , Transcrição Gênica , Transgenes
18.
Exp Mol Med ; 39(6): 722-32, 2007 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-18160843

RESUMO

A trans-splicing ribozyme which can specifically reprogram human telomerase reverse transcriptase (hTERT) RNA was previously suggested as a useful agent for tumor-targeted gene therapy. In this study, we evaluated in vivo function of the hTERT-targeting trans-splicing ribozymes by employing the molecular analysis of expression level of genes affected by the ribozyme delivery into peritoneal carcinomatosis mice model. To this effect, we constructed adenoviral vector encoding the specific ribozyme. Noticeably, more than four-fold reduction in the level of hTERT RNA was observed in tumor nodules by the systemic infection of the ribozyme-encoding virus. Such hTERT RNA knockdown in vivo induced changes in the global gene expression profile, including the suppression of specific genes associated with anti-apoptosis including bcl2, and genes for angiogenesis and metastasis. In addition, specific trans-splicing reaction with the targeted hTERT RNA took place in the tumors established as peritoneal carcinomatosis in mice by systemic delivery of the ribozyme. In conclusion, this study demonstrates that an hTERT-specific RNA replacement approach using trans-splicing ribozyme represents a potential modality to treat cancer.


Assuntos
Expressão Gênica/fisiologia , RNA Catalítico/metabolismo , Telomerase/metabolismo , Trans-Splicing/genética , Animais , Linhagem Celular , Vetores Genéticos , Humanos , Camundongos , Metástase Neoplásica , Neoplasias/genética , Neoplasias/patologia , RNA Catalítico/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Telomerase/antagonistas & inibidores , Telomerase/genética
19.
FEBS Lett ; 580(21): 5033-43, 2006 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-16949075

RESUMO

For suicide gene therapy to be successfully applied for clinical settings, cancer-restricted expression of such suicide gene should be required. We previously showed that group I intron from Tetrahymena can induce new RNA that exerts anti-cancer activity through RNA replacement by trans-splicing reaction with high fidelity and specificity onto targeted human telomerase reverse transcriptase (hTERT) RNA in cancer cells, and hence the ribozyme can selectively retard growth of the cells in vivo as well as in vitro. However, the shortage of complete tumor-selectivity due to telomerase expression of highly proliferating normal cells can limit therapeutic applicability of the hTERT-targeting approach. In this study, to explore the possibility of improving specificity of cancer therapy, we have attempted to stimulate anticancer gene activity specifically in liver cancer cells by tissue-specific expression of the hTERT-targeting trans-splicing ribozyme using liver-specific promoters. Transient transfection experiments demonstrated that the expression of transgene such as luciferase gene was specifically and highly triggered from hTERT-expressing liver cancer cells transfected with the ribozyme. Moreover, liver-specific expression of the ribozyme with diphtheria toxin A or herpes simplex virus thymidine kinase gene as 3' exon could specifically and highly retard the growth of the hTERT-expressing liver cancer cells. In conclusion, we can greatly improve specificity of cancer cytotoxicity by combination of transcriptional targeting for tissue-specific transgene expression with RNA replacement for cancer-specific anticancer gene induction.


Assuntos
Neoplasias/patologia , RNA Catalítico/metabolismo , Trans-Splicing/genética , Sequência de Bases , Morte Celular/fisiologia , Sobrevivência Celular/fisiologia , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Genes Transgênicos Suicidas/genética , Células HT29 , Células HeLa , Humanos , Fígado/metabolismo , Luciferases/genética , Dados de Sequência Molecular , Especificidade de Órgãos , Regiões Promotoras Genéticas/genética , Telomerase/metabolismo , Timidina Quinase/metabolismo , Ativação Transcricional , Células Tumorais Cultivadas
20.
Gene ; 294(1-2): 141-6, 2002 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-12234675

RESUMO

We report cloning a cDNA that encodes a novel short-chain dehydrogenase/reductase, SDR-O, conserved in mouse, human and rat. Human and mouse liver express SDR-O (short-chain dehydrogenase/reductase-orphan) mRNA intensely. The mouse embryo expresses SDR-O mRNA as early as day seven. Human SDR-O localizes on chromosome 12; mouse SDR-O localizes on chromosome 10 with CRAD1, CRAD2 and RDH4. SDR-O shares highest amino acid similarity with rat RoDH1 and mouse RDH1 (69-70%), but does not have the retinol and 3alpha-hydroxysteroid dehydrogenase activity of either, nor is it active as a 17beta- or 11beta-hydroxysteroid dehydrogenase. Short-chain dehydrogenase/reductases catalyse the metabolism of ligands that bind with nuclear receptors: the occurrence of 'orphan' nuclear receptors may imply existence of 'orphan' SDR, suggesting that SDR-O may catalyse the metabolism of another class of nuclear receptor ligand. Alternatively, SDR-O may not have a catalytic function, but may regulate metabolism by binding substrates/products and/or by serving as a regulatory factor.


Assuntos
Cromossomos Humanos Par 12/genética , Cromossomos/genética , Oxirredutases/genética , Sequência de Aminoácidos , Animais , Células CHO , Mapeamento Cromossômico , Clonagem Molecular , Cricetinae , DNA Complementar/química , DNA Complementar/genética , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Oxirredutases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Sintenia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA