RESUMO
OBJECTIVE: Body piercing is defined as the penetration of jewellery into openings made in different body areas. In the last decades, it has become increasingly common in the general population. The aim is to analyse the available literature about complications from body piercing for contributing to raise the awareness towards this issue and to plan and perform appropriate prevention interventions. STUDY DESIGN: This is a systematic review. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to perform this systematic review; the protocol was registered with PROSPERO [CRD42020177972]. PubMed, Scopus and Web of Science were searched from database inception to April 2020, and articles in English language reporting a proven association between piercings and health risks were included, and their quality were assessed by adequate quality assessment tools. RESULTS: A total of 4748 studies were found, and after duplicates removal and screening, 84 articles were included. Studies dealing with microbiological effects reported these complications both locally and at distant sites as a result of the spreading of the primary site infection: mastitis, endocarditis, glomerulonephritis, cephalic tetanus, viral hepatitis, HIV, cerebellar brain abscess and toxic shock syndrome. In addition, bleeding, gingival recession, dental injuries, contact dermatitis, granulomatous dermatitis, keloid, fibroma and basal cell carcinoma were reported. CONCLUSIONS: Health authorities should promote educational campaigns to spread the knowledge on health risks related to piercings. Besides, piercers are often not adequately aware of all the possible adverse effects due to piercings because their professional training differs among countries. It is therefore advisable to provide periodical upgrade of their education in this field.
Assuntos
Piercing Corporal , Piercing Corporal/efeitos adversos , Feminino , HumanosRESUMO
BACKGROUND: The literature shows that gut microbiota composition is related with health, and a lot of individual and outer factors may determine its variability. In particular, nutrition and exercise seem to influence the presence in the gut of the two major bacterial phyla of Firmicutes and Bacteroidetes. STUDY DESIGN: An ongoing cross-sectional investigation is aimed to explore these associations in humans. METHODS: Healthy Caucasian young adults were asked to provide a fecal sample in order to analyze their gut microbiome considering their Body Mass Index (BMI), adherence to Mediterranean diet and Physical Activity (PA) level. RESULTS: A total of 59 participants (49.1% males, mean age 23.1 ± 3.14 years) were enrolled so far. Firmicutes (61.6±14.6) and Bacteroidetes (30.7 ± 13.3) showed the highest relative abundance in fecal samples. The Pearson's analysis showed a significant negative correlation between PA and Firmicutes (r =-0.270, p = 0.03). Linear regression confirmed a significant decrease of this phylum with the increase of PA (R2 = 0.07, p = 0.03). CONCLUSIONS: These preliminary results suggest the association between physical activity and gut microbiota composition in healthy humans.
Assuntos
Bacteroidetes/isolamento & purificação , Dieta Mediterrânea , Exercício Físico , Firmicutes/isolamento & purificação , Microbioma Gastrointestinal , Adulto , Estudos Transversais , Fezes/microbiologia , Feminino , Humanos , Masculino , Projetos Piloto , Valores de Referência , Adulto JovemRESUMO
OBJECTIVE: S100 proteins are demonstrated to exert a protective role in the gastrointestinal tract. In the present study, we investigated whether S100B protein, that is typically expressed by enteroglial cells, is detectable in feces and could be a useful noninvasive indicator of gut chronic inflammation. PATIENTS AND METHODS: This clinical prospective study included n=48 patients suffering Crohn's disease (CD) or ulcerative colitis (UC) and non IBD-controls. The clinical disease activity was evaluated using Harvey-Bradshaw or Mayo Score Index while the diagnosis of IBD was defined based on standard endoscopic and histological criteria. S100B and calprotectin were extracted and analyzed using commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Unlike calprotectin, S100B was significantly decreased in both CD and UC compared to non IBD-patients. The strongest quantitative alterations of S100B were detected concomitantly with signs of active or quiescent disease, including high/normal expression of fecal calprotectin, mucosal damage/cryptitis, mucin depletion and inflammatory infiltrate, as defined by endoscopic evaluation and histological analysis. At the onset of disease and under no Infliximab-based therapy, the lowest was detected suggesting that S100B in feces could have a potential diagnostic value for IBD. CONCLUSIONS: Testing for S100B and calprotectin could be a useful screening tool to better predict IBD activity.
Assuntos
Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Fezes/química , Subunidade beta da Proteína Ligante de Cálcio S100/análise , Adulto , Idoso , Biomarcadores/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
INTRODUCTION: Doping is an important public health problem widespread not only among elite athletes, but also among amateur and recreational athletes and the general population. In Italy the introduction of doping prevention within the Essential Levels of Care (LEA) with the DPCM 12/1/2017 represents a crucial step towards the implementation of education and health promotion interventions. In this context, the Departments of Prevention (DP) of the Local Health Authorities (LHA) have to play a fundamental role, becoming the cultural and operational reference on this issue. As part of the "Doping prevention: development of a permanent educational tool coordinated by the National Health Service Prevention Departments" project, funded by the Italian Ministry of Health, a survey was conducted on the activities carried out by the DP regarding doping prevention and improper use and abuse of drugs and food supplements in sports and physical activities, as a basis for the harmonization of organizational structures and prevention programs and the creation of a collaboration network at a regional and national level. METHODS: A semi-structured questionnaire consisting of 11 questions, prepared on an electronic platform, was sent to the DP of all the Italian LHA. RESULTS: A total of 38 DP out of 131 (29%) completed the questionnaire, with representation from all regions. 42.1% of DP carried out or are still running programs for the prevention of doping, a percentage that decreases to 27% considering the programs for the prevention of misuse and abuse of drugs and food supplements in sports and in physical activities; in less than half of the DP, 37.5% and 41.7%, respectively, dedicated funds have been allocated. The professionals most involved in prevention of doping are the Specialists in Sport Medicine (81.3%) followed by Specialists in Hygiene (43.8%) and Psychologists (37.5%), while Health Care Assistants (50%) are the professionals most involved in the prevention of the improper use of drugs and food supplements, followed by Specialists in Hygiene and Specialists in Sport Medicine (40%). Most of the DP (71.9%) believe that the introduction of programs to prevent and counteract doping in the LEA will have repercussions on their approach against doping. CONCLUSIONS: The survey, although conducted on a limited sample, has provided an important framework relating to programs for the prevention of doping and the misuse and abuse of drugs and food supplements in sports and in the physical activities carried out by DP. A remarkable heterogeneity has been highlighted, both at national and regional level. It is urgent to provide DP with homogeneous and effective organizational models and adequate operational tools, paying particular attention to the training of all the professionals involved. It is also essential to implement permanent monitoring tools.
Assuntos
Suplementos Nutricionais , Dopagem Esportivo/prevenção & controle , Promoção da Saúde/organização & administração , Saúde Pública/métodos , Atletas , Humanos , Itália , Medicina Estatal/organização & administração , Inquéritos e QuestionáriosRESUMO
When planning actions to prevent doping in the general population, public health operators may collide against the interests of criminal organizations involved in illicit trafficking of drugs. In addition to technical and professional expertise, or clinical and pharmacological skills, also a deep knowledge of legal and social issues is strongly required to face the problem and assure the effectiveness of the preventive actions. Sports competitions, athletes training or adapted physical activity may all represent conditions and environments at risk for misusing or abusing drugs and dietary supplements. A correct approach to sport and physical activity implies respect of competition rules, attention to own body limits and knowledge of risk factors. Health education campaigns and preventive actions should also consider education to legality in the different settings. The comprehension of the complex net that is available to access doping, locally or globally through online Internet sites, is essential as well as the awareness of the huge economic burden of crime interests behind the illicit trafficking of drugs. A modern whole rounded approach needs to consider doping not only as a violation of sport rules but also of the own body health, representing almost a form of addiction involving individuals and communities, and being supported by crime. Within this frame, doping is considered not just as a sport violation or a risk factor for individual's health, but as a disease of the society, in the society, against the society. A peculiar equilibrium seems to prevail between crime external pressures and resigned internal acceptance, according to the 'mafia hypothesis' model, where hosts accept parasitism to avoid retaliation. Here, main contributes and topics from the Erice 53rd Course are summarized and reviewed, providing links and references for further studies in the field. Health education and education to legality represent two sides of a same question, concerning both the general population and the health authorities. In conclusion, education to legality is a key component for prevention of doping and a priority for public health operators involved in protecting population health.
Assuntos
Dopagem Esportivo/prevenção & controle , Tráfico de Drogas/prevenção & controle , Educação em Saúde/métodos , Saúde Pública , Atletas , Suplementos Nutricionais , Dopagem Esportivo/legislação & jurisprudência , Tráfico de Drogas/legislação & jurisprudência , Humanos , Drogas Ilícitas/legislação & jurisprudência , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controleRESUMO
BACKGROUND: Inactive lifestyles are a key risk factor underpinning the development of many chronic diseases, yet more than half of the Italian population does not meet WHO thresholds for at least moderate physical activity. This study aims to make the economic case to upscale investments in policy actions to promote exercise and physical activity. STUDY DESIGN: Modelling-based cost-effectiveness analysis in Italy. METHODS: The study assesses the impact on health and healthcare expenditure of seven public health policies to promote exercise and physical activity against a business as usual scenario. Assessed policies include: promotion of active transport, workplace sedentarily interventions, investments in sports and recreation, mass media campaigns, prescription of physical activity in primary care, school-based interventions and mobile apps. RESULTS: Public policies to promote exercise have the potential to improve population health and produce savings in healthcare expenditure. Assessed policies can avoid hundreds of cases of cardiovascular diseases and diabetes per year and tens of cases of cancer resulting in gains in DALYs in the order of thousands per year. In the medium-term, the vast majority of policies show excellent cost-effectiveness ratio, below internationally recognized thresholds. CONCLUSIONS: Investing in policies to promote active lifestyles is a good investment for Italy.
Assuntos
Exercício Físico/fisiologia , Política de Saúde , Promoção da Saúde/métodos , Política Pública , Análise Custo-Benefício , Gastos em Saúde/estatística & dados numéricos , Promoção da Saúde/economia , Humanos , Itália , Estilo de Vida , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco , Comportamento SedentárioRESUMO
The gut microbiota is implicated in digestive, metabolic and immune processes of the host. The physiological and pathophysiological functions of the intestinal microbiota depend of its composition, and several individual or external factors may be associated with the presence of some categories, phyla or species of microorganisms in the gut. In particular, two bacterial phyla - Firmicutes and Bacteroidetes - are predominant in the human gut and their relative concentrations seem to be related with age, gender, diet habits and weight status. In the last decade, several studies have tried to characterize the possible role of physical activity in determining qualitative and quantitative composition of the intestinal microbiota. This review is aimed at exploring the current evidences regarding the association between physical activity and gut microbiota composition in animal models and in the humans. Further studies are needed to clarify the mutual relationships among exercise, diet, nutritional supplements/doping agents and gut microbiota.
Assuntos
Dieta , Exercício Físico/fisiologia , Microbioma Gastrointestinal/fisiologia , Animais , Bacteroidetes/fisiologia , Firmicutes/fisiologia , HumanosRESUMO
BACKGROUND: Healthcare associated infections (HAIs) represent a serious problem for public health, as they increase the morbidity and mortality rates, present a relevant financial burden, and significantly contribute to the antimicrobial resistance. METHODS: The aim of this review was to investigate the literature about HAIs, with particular reference to hospital environments and the role of cleaning and disinfection procedures. Hospital environments are an essential reservoir for HAIs cross transmission, and the application of appropriate procedures related to hand hygiene and disinfection/sterilization of surfaces and instruments remain key strategies for controlling HAIs. RESULTS: Different procedures, based on the risk associated with the healthcare procedure, are recommended for hand hygiene: washing with soap and water, antiseptic rubbing with alcohol-based disinfectants, antiseptic and surgical hand washing. Environmental surfaces can be treated with different products, and the mostly used are chlorine-based and polyphenolic disinfectant. The reprocessing of instruments is related to their use according to the Spaulding's classification. In addition, scientific evidence demonstrated the great relevance of the "bundles" (small set of practices performed together) in controlling HAIs. CONCLUSIONS: Research agenda should include the improvement of well-known effective preventive procedures and the development of new bundles devoted to high-risk procedures and specific microorganisms.
Assuntos
Infecção Hospitalar/prevenção & controle , Desinfecção/métodos , Contaminação de Equipamentos/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/transmissão , Desinfetantes/química , Desinfecção das Mãos/métodos , Hospitais/normas , Humanos , Saúde PúblicaRESUMO
BACKGROUND: Exposure to single and multiple carcinogenic metals and/or semimetals represents a major environmental risk factor for public health. In particular, children are more susceptible to environmental pollutants than adults, but specific studies are still limited. The aims of the present study were: 1) to trace the exposure and co-exposure profiles to eight known or suspected carcinogenic metals and semimetals (As, Be, Cd, Co, Cr, Ni, Pb, and Sb); and: 2) to evaluate the influence of some possible interfering/confounding factors on the exposure to these elements during childhood. STUDY DESIGN: Cross-sectional study. METHODS: We recruited 159 healthy Italian children attending a primary school of the urban area of Rome, Italy. Selected metals were determined by inductively coupled plasma mass spectrometry on urinary samples collected at the end of a "typical" day (one sample for each child), while information about possible confounding/interfering factors were collected via questionnaires. RESULTS: The great part of the studied children resulted co-exposed to the monitored metals: 83.2%, 69.2%, 51.0% and 29.3% of the participants were concurrently exposed to at least two, three, four and five trace elements, respectively. Gender was the only one among the investigated variable that significantly influenced the co-exposure, with females resulting at lower risk (OR = 0.392; 95 IC = 0.156 - 0.989; p < 0.047). CONCLUSIONS: Given the importance of protecting child's health and the risks related to the exposure to carcinogenic metals, especially when they occur simultaneously, other researches in this field are strongly recommended.
Assuntos
Carcinógenos Ambientais/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Saúde da População Urbana , Criança , Estudos Transversais , Feminino , Humanos , Itália , MasculinoRESUMO
Administration of prohibited substances to enhance athletic performance represents an emerging medical, social, ethical and legal issue. Traditional controls are based on direct detection of substances or their catabolites. However out-of-competition doping may not be easily revealed by standard analytical methods. Alternative indirect control strategies are based on the evaluation of mid- and long-term effects of doping in tissues. Drug-induced long-lasting changes of gene expression may be taken as effective indicators of doping exposure. To validate this approach, we used real-time PCR to monitor the expression pattern of selected genes in human haematopoietic cells exposed to nandrolone, insulin-like growth factor I (IGF-I) or growth hormone (GH). Some candidate genes were found significantly and consistently modulated by treatments. Nandrolone up-regulated AR, ESR2 and PGR in K562 cells, and SRD5A1, PPARA and JAK2 in Jurkat cells; IGF-I up-regulated EPOR and PGR in HL60 cells, and SRD5A1 in Jurkat; GH up-regulated SRD5A1 and GHR in K562. GATA1 expression was down-regulated in IGF-1-treated HL60, ESR2 was down-regulated in nandrolone-treated Jurkat, and AR and PGR were down-regulated in GH-treated Jurkat. This pilot study shows the potential of molecular biology-based strategies in anti-doping controls.
Assuntos
Anabolizantes/farmacologia , Dopagem Esportivo , Marcadores Genéticos/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Hormônio do Crescimento Humano/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia , Nandrolona/farmacologia , Detecção do Abuso de Substâncias/métodos , Anabolizantes/administração & dosagem , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Quimioterapia Combinada , Células HL-60 , Células-Tronco Hematopoéticas/efeitos dos fármacos , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Fator de Crescimento Insulin-Like I/administração & dosagem , Itália , Células Jurkat , Células K562 , Nandrolona/administração & dosagem , Projetos Piloto , Reação em Cadeia da Polimerase/métodos , Estudos Prospectivos , Reprodutibilidade dos Testes , Detecção do Abuso de Substâncias/estatística & dados numéricos , Regulação para Cima/efeitos dos fármacosRESUMO
Ets genes are transcription factors expressed in different tissues. Biochemical pathways interfering with the intracellular calcium ion concentration are known to influence members of this gene family. Considering experimental observations and previous reports, we proposed a hypothetical model of interaction between EMF and Ets, based on possible interference in pathways involving calcium as a second messenger. This approach comprehend different hypothesis and may contribute to clarify EMF biological effects, providing an experimental model and a procedure based on gene expression analysis. Additional knowledge on biological mechanisms is required to support these promising results. Further experiments are in progress to assess the role of EMF in modulating gene expression and its biological meaning. Identification of early endpoints is needed for mechanism understanding and development of sensitive biomarkers for molecular epidemiology studies.
Assuntos
Campos Eletromagnéticos , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Animais , Células Cultivadas/efeitos da radiação , Campos Eletromagnéticos/efeitos adversos , Expressão Gênica , Camundongos , Camundongos Endogâmicos BALB C , Biologia Molecular , Epidemiologia Molecular , Proteínas Proto-Oncogênicas c-ets , RNA Mensageiro/genética , RNA Mensageiro/efeitos da radiação , Transcrição Gênica , Células Tumorais Cultivadas/efeitos da radiaçãoRESUMO
We have previously shown that electromagnetic field (EMF) exposure induces ETS1 oncogene overexpression in different cell lines. In order to investigate in vivo EMF effects, BALB/c mice were exposed at different times to 50 MHz radiation, modulated (80%) at 16 Hz. The exposed and control animals were sacrificed and the spleen excised for rt-pcr and western blot analysis. We observed an increase in ETS1 mRNA and protein expression, but a decrease in ETS2 protein levels. Preliminary results from this experimental model show in vivo evidence of the effect of EMF on ETS oncogene expression.
Assuntos
Proteínas de Ligação a DNA , Campos Eletromagnéticos/efeitos adversos , Regulação da Expressão Gênica , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras , Transativadores/genética , Fatores de Transcrição/genética , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteína Proto-Oncogênica c-ets-1 , Proteína Proto-Oncogênica c-ets-2 , Proteínas Proto-Oncogênicas c-ets , RNA MensageiroRESUMO
The use of antiblastic drugs has opened up new perspectives in improvement of therapy and life quality for cancer patients. The widespread clinical application of cytostatic drugs implies risks for exposed hospital personnel, due to genotoxic and toxic-reproductive effects. Biological monitoring is fundamental to identify individuals at risk but is limited by the long latency of chronic effects, absence of unique cellular targets and low sensitivity of available laboratory tests. The objective of this study was to investigate toxic mechanisms by a molecular biology approach, searching for biomarkers potentially useful in monitoring programs. The proposed experimental model consisted of cell line exposure to cyclophosphamide, an alkylating agent of wide clinical use. Cellular response has been investigated focusing on potential targets at RNA level, through reverse transcription polymerase chain reaction (RT-PCR) and differential display analysis. We studied the expression of several genes involved in differentiation, apoptosis and chemoresistance: ets1, bax, bcl-2, bag-1, bcl-X, mdr1 and mrp. Specific patterns of mRNA modulations were observed. Differential display analysis revealed candidate genes induced or repressed following exposure: their characterization is in progress. Besides improving the understanding of toxic mechanisms, identification of modulated molecular targets opens up new perspectives in exposure risk assessment, biomonitoring and preventive strategies at occupational level.
Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Ciclofosfamida/efeitos adversos , Pessoal de Saúde , Exposição Ocupacional/efeitos adversos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Antineoplásicos Alquilantes/farmacologia , Apoptose/genética , Biomarcadores , Proteínas de Transporte/genética , Linhagem Celular , Ciclofosfamida/farmacologia , Proteínas de Ligação a DNA , Regulação da Expressão Gênica/efeitos dos fármacos , Nível de Saúde , Humanos , Camundongos , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Proteína Proto-Oncogênica c-ets-1 , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-ets , Fatores de Risco , Fatores de Transcrição/genética , Transcrição Gênica/efeitos dos fármacos , Células Tumorais Cultivadas , Proteína X Associada a bcl-2 , Proteína bcl-XRESUMO
We have analyzed gene expression in hemopoietic and testicular cell types after their exposure to 50 MHz radiofrequency (RF) non-ionizing radiation modulated (80%) with a 16 Hz frequency. The exposure system generates a 0.2 microT magnetic field parallel to the ground and a 60 V/m electric field orthogonal to the earth's magnetic field. Exposure conditions were selected so as to interfere with the calcium ion flow. Under these electromagnetic field (EMF) conditions, we observed an overexpression of the ets1 mRNA in Jurkat T-lymphoblastoid and Leydig TM3 cell lines. This effect was observed only in the presence of the 16 Hz modulation, corresponding to the resonance frequency for calcium ion with a DC magnetic field of 45.7 microT. We have also identified a putative candidate gene repressed after EMF exposure. The experimental model described in this paper may contribute to the understanding of the biological mechanisms involved in EMF effects.
Assuntos
Campos Eletromagnéticos , Oncogenes/efeitos da radiação , Proteínas Proto-Oncogênicas/genética , Ondas de Rádio , Fatores de Transcrição/genética , Transcrição Gênica/efeitos da radiação , Animais , Linhagem Celular , Neoplasias do Colo , Células HL-60 , Humanos , Células Jurkat , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/efeitos da radiação , Masculino , Camundongos , Proteína Proto-Oncogênica c-ets-1 , Proteínas Proto-Oncogênicas c-ets , RNA Mensageiro/genética , Testículo , Células Tumorais CultivadasRESUMO
We characterized a new human ATP-binding cassette (ABC) transporter gene that is highly expressed in the placenta. The gene, ABCP, produces two transcripts that differ at the 5' end and encode the same 655-amino acid protein. The predicted protein is closely related to the Drosophila white and yeast ADP1 genes and is a member of a subfamily that includes several multidrug resistance transporters. ABCP, white, and ADP1 all have a single ATP-binding domain at the NH2 terminus and a single COOH-terminal set of transmembrane segments. ABCP maps to human chromosome 4q22, between the markers D4S2462 and D4S1557, and the murine gene (Abcp) is located on chromosome 6 28-29 cM from the centromere. ABCP defines a new syntenic segment between human chromosome 4 and mouse chromosome 6. The abundant expression of this gene in the placenta suggests that the protein product has an important role in transport of specific molecule(s) into or out of this tissue.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Cromossomos Humanos Par 4 , Resistência a Múltiplos Medicamentos/genética , Placenta/fisiologia , Transportadores de Cassetes de Ligação de ATP/biossíntese , Sequência de Aminoácidos , Animais , Mapeamento Cromossômico , DNA Complementar/genética , Humanos , Camundongos , Dados de Sequência Molecular , Especificidade de Órgãos , Placenta/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Using differential display method, we have isolated and characterized a novel gene, N8, encoding an approximately 24 kDa protein. It is located on human chromosome 8q13 region. N8 gene is expressed at high levels in tumor derived cell lines from multiple cancers. It is also expressed at higher levels in lung tumors than normal lung tissue. N8 is also differentially expressed in fetal and adult tissues. In adult, N8 is expressed at high levels in brain, kidney, prostate, pancreas and intestine and at very low levels in lung, liver, hematopoietic cells and gonads. During murine embryonic development N8 is expressed in the epithelium of the intestine, stomach, olfactory epithelium, neuronal layers of retina, kidney and salivary gland. Taken together, these results suggest that N8 may play different roles during embryogenesis and in the adult animals.
Assuntos
Cromossomos Humanos Par 8 , Proteínas de Neoplasias/genética , Neoplasias/genética , Proteínas Repressoras/genética , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Linhagem Celular , Mapeamento Cromossômico , Sequência Consenso , Primers do DNA , DNA Complementar , Feminino , Expressão Gênica , Humanos , Hibridização In Situ , Cariotipagem , Zíper de Leucina , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Masculino , Dados de Sequência Molecular , Neoplasias/patologia , Especificidade de Órgãos , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Células Tumorais CultivadasRESUMO
We have ectopically expressed transcription factor ETS1 in two different highly tumorigenic human colon cancer cell lines, DLD-1 and HCT116, that do not express endogenous ETS1 protein and have obtained several independent clones. The expression of wild-type ETS1 protein in these colon cancer cells reverses the transformed phenotype and tumorigenicity in a dose-dependent manner. By contrast, expression in DLD-1 cells of a variant form of ETS1, lacking transcriptional activity, did not alter the tumorigenic properties of the cells, suggesting that the reduction in tumorigenicity in these clones was specific for the wild-type ETS1 gene products. Since these colon cancer cells have multiple genetic alterations, the system described in this paper could be a good model to study the suppression of tumorigenicity at a transcriptional level, which could lead to the design and development of novel drugs for cancer treatment.
Assuntos
Neoplasias do Colo/patologia , Mutação Puntual , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Primers do DNA , Humanos , Dados de Sequência Molecular , Família Multigênica , Fases de Leitura Aberta , Reação em Cadeia da Polimerase , Proteína Proto-Oncogênica c-ets-1 , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ets , Proteínas Recombinantes/biossíntese , Transfecção , Células Tumorais CultivadasRESUMO
The ETS1 gene encodes a sequence-specific transcription factor binding to purine-rich DNA sequences (-GGAA-) present in the transcriptional regulatory regions of many cellular and viral promoters/enhancers, including many lymphokine genes. The ETS1 gene is expressed at high levels in resting T cells and at very low levels after T cell activation, suggesting it may suppress the expression of genes induced during T cell activation. To find out if ETS1 regulates expression of the IL-2 gene, we have ectopically expressed antisense (AS) ETS1 in Jurkat T cells to block the formation of ETS1 proteins. AS ETS1 transfectants produce higher levels of IL-2 compared with sense ETS1 transfectants. Expression of ETS1 DNA binding domain in Jurkat T cells also decreased the production of IL-2. In AS ETS1 transfectants, IL-2 formation was completely inhibited by cyclosporin A and FK590. The IL-2 promoter linked to a chloramphenicol acetyl transferase reporter gene has high activity in AS ETS1 transfectants, indicating that increased IL-2 production seems to be a result of transcriptional induction. Taken together, these results suggest the possibility that ETS1 may act as a negative regulator of IL-2 gene transcription and provide a rational approach toward engineering the endogenous expression of IL-2 in T cells.
Assuntos
Regulação da Expressão Gênica/genética , Interleucina-2/biossíntese , Interleucina-2/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição , Linhagem Celular , Cloranfenicol O-Acetiltransferase/genética , Humanos , Ionomicina/farmacologia , Regiões Promotoras Genéticas/genética , Proteína Proto-Oncogênica c-ets-1 , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/fisiologia , Proteínas Proto-Oncogênicas c-ets , Acetato de Tetradecanoilforbol/farmacologia , Transcrição Gênica/genética , Transfecção/genéticaRESUMO
The epitope for E44 monoclonal antibody (mAb) was mapped using mutated ETS1 proteins lacking different carboxy-terminal regions and by the employment of synthetic oligopeptides spanning the epitope region. This epitope lies around Arg211 of the human ETS1 protein since substitution of Arg211 by Gln211 in the epitope region results in the loss of recognition of the mouse ETS1 protein by E44 mAb. Substitution of Leu214 by valine214 in the epitope region (as is found in the chicken ETS1 and viral Ets proteins) does not alter the capacity of the E44 mAb to recognize this antigen. Taken together, these results suggest that a specific ionic interaction is able to play a pivotal role in the recognition of the ETS1 protein by the E44 mAb.
Assuntos
Anticorpos Monoclonais/imunologia , Epitopos/imunologia , Fragmentos de Peptídeos/imunologia , Proteínas Proto-Oncogênicas/imunologia , Fatores de Transcrição , Sequência de Aminoácidos , Western Blotting , Humanos , Dados de Sequência Molecular , Mapeamento de Peptídeos , Proteína Proto-Oncogênica c-ets-1 , Proteínas Proto-Oncogênicas c-ets , Células Tumorais CultivadasRESUMO
We studied the correlation between dexamethasone (Dex) induced growth effects and modulation of epidermal growth factor receptor (EGFR) expression in OVCA 433 ovarian cancer cells. These cells express specific high and low affinity 125I-EGF binding sites and are growth stimulated by EGF. Dex exhibits mitoinhibitory effects by recruiting OVCA 433 cells in the G0-G1 phase of the cycle, but increases the number of both the high and the low affinity EGFR in a dose dependent manner. The maximal EGFR expression increase occurs after 24 h of Dex treatment consistently with Northern blot studies. The mitogenic activity of EGF in OVCA 433 cells is not affected by the presence of Dex. Moreover Dex growth inhibition occurs in JA1 cells, an ovarian cancer cell line which expresses unfunctional EGFR and which is unresponsive to EGF. Our results indicate that the Dex induced growth effects occur independently of EGFR expression.