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OBJECTIVE: Colorectal cancer (CRC) is the most common malignancy for cancer-associated death. This study aimed to investigate the effects of microRNA-124 (miR-124) on tumor proliferation of CRC in vivo and in vitro. MATERIALS AND METHODS: MiR-124 mimics were synthesized and transfected into SW620 cells, which were divided into SW620, microRNA-normal control (miR-NC) and miR-124 mimics group. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine miR-124, chemokine (C-C motif) ligand-20 (CCL20), tankyrase-2 (TNKS2), phospholipase Cbeta1 (PLCB1) and Wnt4. Cell counting kit-8 (CCK-8) was employed to evaluate cell proliferation. The interaction between miR-124 and PLCB1 was tested with the Dual-Luciferase assay. Cell cycle, apoptosis and invasion were also evaluated. CRC xenograft mouse model was established and tumor size was measured. Hematoxylin and eosin (HE) was used to examine inflammation. Western blot was utilized to detect Wnt4. RESULTS: MiR-124 was over-expressed in SW620 cells, significantly reduced CCL20 and enhanced TNKS2 compared to that of the miR-NC group (p<0.05). MiR-124 might play roles by initiating PLCB1 expression. MiR-124 significantly decreased cell viability compared to the miR-NC group (p<0.05). MiR-124 regulated cell cycle and markedly induced apoptosis and inhibited cell invasion compared to the miR-NC group (p<0.05). MiR-124 significantly decreased tumor size of CRC models compared to miR-NC mice (p<0.05). MiR-124 remarkably alleviated inflammation of tumor tissues. MiR-124 markedly enhanced Wnt4 expression compared to the miR-NC group (p<0.05). CONCLUSIONS: MiR-124 inhibited tumor cell proliferation in vitro and suppressed tumor growth in vivo by interacting with PLCB1 and regulating the Wnt/ß-catenin signaling pathway.
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Neoplasias Colorrectales/terapia , Terapia Genética/métodos , MicroARNs/genética , Fosfolipasa C beta/genética , Vía de Señalización Wnt/genética , Animales , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Femenino , Humanos , Ratones , MicroARNs/agonistas , MicroARNs/metabolismo , Oligonucleótidos/administración & dosificación , Transfección , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina/metabolismoRESUMEN
OBJECTIVE: To examine the associations between personality traits and suicidal ideation (SI) and attempt (SA) in mood disorder patients and community controls. METHOD: We recruited 365 bipolar, 296 major depressive disorder patients, and 315 community controls to assess their lifetime suicidality. Participants filled out self-reported personality questionnaires to collect data of personality traits, including novelty seeking (NS), harm avoidance (HA), extraversion (E), and neuroticism (N). We used logistic regression models adjusted for diagnoses to analyze combinational effects of personality traits on the risk of suicide. Additionally, radar charts display personality profiles for suicidal behaviours by groups. RESULTS: All personality traits were associated with the risk of suicidality with various effect size, except for E that showed protective effect. High N or HA had prominent and independent risk effects on SI and SA. Combinations of high N and low E, or high HA and NS were the risk personality profiles for suicidality. Higher N scores further distinguished SA from SI in mood disorder patients. CONCLUSION: Introvert personality traits showed independent risk effects on suicidality regardless of diagnosis status. Among high-risk individuals with suicidal thoughts, higher neuroticism tendency is further associated with increased risk of suicide attempt.
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Trastorno Bipolar/psicología , Trastorno Depresivo Mayor/psicología , Personalidad , Ideación Suicida , Intento de Suicidio/psicología , Adulto , Estudios de Casos y Controles , Conducta Exploratoria , Extraversión Psicológica , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neuroticismo , Factores de Riesgo , Suicidio/psicología , Suicidio/estadística & datos numéricos , Intento de Suicidio/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 and JQ1 synergistically caused an arrest of tumor cells at the G2/M phase and a decrease in the XIAP-linked cell survival. Our subsequent mechanistic analyses indicate that this functional cooperation was strongly associated with the concomitant disruption of activation or expression of FAK and c-Myc as well as their downstream signaling through the PI3K/Akt pathway. In line with these observations, we detected a strong co-amplification or upregulation at genomic or protein level for FAK and c-Myc in a large portion of primary tumors in the TCGA or a local HGSOC patient cohort. Taken together, our results suggest that the integrin-FAK signaling axis and c-Myc synergistically drive cell proliferation, survival and oncogenic potential in HGSOC. As such, our study provides key genetic, functional and signaling bases for the small-molecule-based co-targeting of these two distinct oncogenic drivers as a new line of targeted therapy against human ovarian cancer.
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This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.
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Adulto , Femenino , Humanos , Masculino , Agotamiento Profesional/genética , Enfermedades en Gemelos/genética , Lugar de Trabajo , Agotamiento Profesional/epidemiología , Agotamiento Profesional/etiología , Agotamiento Profesional/psicología , Demografía , Enfermedades en Gemelos/epidemiología , Enfermedades en Gemelos/etiología , Enfermedades en Gemelos/psicología , Interacción Gen-Ambiente , Sistema de Registros , Factores de Riesgo , Encuestas y Cuestionarios , Suecia/epidemiologíaRESUMEN
This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.
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Antioxidantes/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Umbeliferonas/uso terapéutico , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Neoplasias Experimentales , Distribución AleatoriaRESUMEN
A well-behaved spin-light emitting diode (LED) composed of InGaN/GaN multiple quantum disks (MQDs), ferromagnetic contact, and Fe3O4 nanoparticles has been designed, fabricated, and characterized. The degree of circular polarization of electroluminescence (EL) can reach up to a high value of 10.9% at room temperature in a low magnetic field of 0.35 T, which overcomes a very low degree of spin polarization in nitride semiconductors due to the weak spin-orbit interaction. Several underlying mechanisms play significant roles simultaneously in this newly designed device for the achievement of such a high performance. Most of all, the vacancy between nanodisks can be filled by half-metal nanoparticles with suitable energy band alignment, which enables selective transfer of spin polarized electrons and holes and leads to the enhanced output spin polarization of LED. Unlike previously reported mechanisms, this new process leads to a weak dependence of spin relaxation on temperature. Additionally, the internal strain in planar InGaN/GaN multiple quantum wells can be relaxed in the nanodisk formation process, which leads to the disappearance of Rashba Hamiltonian and enhances the spin relaxation time. Our approach therefore opens up a new route for the further research and development of semiconductor spintronics.
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The quantum efficiency and carrier lifetime that decide the photoconduction (PC) efficiencies in the metal oxide semiconductor nanowires (NWs) have been investigated. The experimental result surprisingly shows that the SnO2, TiO2, WO3, and ZnO NWs reveal extraordinary quantum efficiencies in common, which are over one to three orders of magnitude lower than the theoretical expectation. The surface depletion region (SDR)-controlled photoconductivity is proposed to explain the anomalous quantum efficiency and its power dependence. The inherent difference between the metal oxide nanostructures such as carrier lifetime, carrier concentration, and dielectric constant leading to the distinct PC performance and behavior are also discussed.
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OBJECTIVE: Because of ethnic differences in metabolic syndrome (MS) criteria, this study aimed to investigate the MS prevalence among patients with schizophrenia or schizoaffective disorder in Taiwan. METHOD: We recruited 650 patients with schizophrenia or schizoaffective disorder from 36 psychiatric institutions. The MS prevalence was assessed based on the modified Adult Treatment Panel (ATP) III criteria for Asians. RESULTS: The overall MS prevalence was 34.9%, with 38.9% in female and 31.5% in male patients respectively. The difference of MS prevalence between our sample and the general population was marked in male patients under 40 years of age and in female patients under 50 years old. Body mass index > or =24 and age over 40 years old are two important risk factors of MS. Female and polypharmacy had marginal significance with the presence of MS. CONCLUSION: Patients with schizophrenia or schizoaffective disorder in Taiwan had a high prevalence of MS, which appeared early in their lives.
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Síndrome Metabólico/epidemiología , Trastornos Psicóticos/epidemiología , Esquizofrenia/epidemiología , Grasa Abdominal , Antipsicóticos/uso terapéutico , Índice de Masa Corporal , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Prevalencia , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Taiwán/epidemiología , Circunferencia de la CinturaRESUMEN
A sequential manual lifting job is defined as a job where workers rotate between a series of manual lifting rotation slots or elements at specified time intervals during the course of a work shift. The original NIOSH lifting equation lacked a method for assessing the physical demands of these types of jobs. This paper presents the sequential lifting index (SLI), a new conceptual method for assessing the physical demands for sequential manual lifting jobs. The new method is similar to the composite lifting index (CLI) method that was provided by NIOSH for assessing multi-task jobs. The SLI method expands upon the methods originally provided by NIOSH by providing a simple method for estimating the relative magnitude of physical stress for sequential manual lifting jobs. It should also be useful in assisting safety and health specialists to prioritize or rank hazardous jobs within a plant.
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Salud Laboral , Levantamiento de Peso , Soporte de Peso , Fenómenos Biomecánicos , Indicadores de Salud , Humanos , Italia , Modelos Teóricos , National Institute for Occupational Safety and Health, U.S. , Medición de Riesgo , Análisis y Desempeño de Tareas , Estados UnidosRESUMEN
The impact of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism on bladder cancer is unknown. We found no clear correlations between the FGFR4 genotype and risk of bladder cancer or pathological parameters. Neither the polymorphism nor TP53 mutation status was an independent predictor of prognosis, but they might act jointly on the disease-specific survival of patients.
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Genes p53/genética , Polimorfismo de Nucleótido Simple/genética , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidad , Anciano , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
Loss of deoxyribonuclease I (Dnase1) function is associated with systemic lupus erythematosus (SLE) in humans and mice; however, no coding mutations in Dnase1 are found in polygenic murine models. Instead, both MRL-lpr strains and NZB/W F1 hybrids are homozygous for T89I missense in the macrophage-DNASE, desoxyribonuclease I-like 3 (Dnase1l3). By in vitro expression studies, this substitution decreases this enzyme's nuclease activity against free DNA by only approximately twofold; however, the mutation has a greater effect on the capacity of media conditioned with Dnase1l3 to confer a barrier to liposomal gene transfection to HeLa cells. The 89I substitution decreases the Dnase1l3 barrier function in vitro by eightfold (P < 0.01). In splenocytes and BM-derived macrophages of SLE mice, while cellular Dnase1l3 levels are induced relative to C57BL/6 (control) mice, levels of FD-nuclease activity are similar. Finally, media conditioned by MRL and NZB/W F1 macrophages, relative to control, contains a weak interferon-gamma (IFN-gamma) inducible Dnase1l3-associated barrier to transfection. This barrier function is hypothesized to reflect the inability of SLE mice to degrade membrane-enveloped DNA-associated antigens, such as apoptotic bodies, which are predicted to stimulate the characteristic autoimmunity of SLE. Our results for these two generally independent models strongly suggest that Dnase1l3 deficiency increases the susceptibility of these mice to polygenic SLE.
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Endodesoxirribonucleasas/deficiencia , Endodesoxirribonucleasas/genética , Lupus Eritematoso Sistémico/enzimología , Mutación Missense , Animales , Femenino , Immunoblotting/métodos , Fragmentos de Inmunoglobulinas/genética , Lupus Eritematoso Sistémico/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Mutantes , Modelos Animales , Análisis de Secuencia de ADN , TransfecciónRESUMEN
During angiogenesis, microvascular endothelial cells (ECs) secrete proteinases that permit penetration of the vascular basement membrane as well as the interstitial extracellular matrix. This study tested the hypothesis that cathepsin S (Cat S) contributes to angiogenesis. Treatment of cultured ECs with inflammatory cytokines or angiogenic factors stimulated the expression of Cat S, whereas inhibition of Cat S activity reduced microtubule formation by impairing cell invasion. ECs from Cat S-deficient mice showed reduced collagenolytic activity and impaired invasion of collagens type I and IV. Cat S-deficient mice displayed defective microvessel development during wound repair. This abnormal angiogenesis occurred despite normal vascular endothelial growth factor and basic fibroblast growth factor levels, implying an essential role for extracellular matrix degradation by Cat S during microvessel formation. These results demonstrate a novel function of endothelium-derived Cat S in angiogenesis.
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Catepsinas/fisiología , Endotelio Vascular/enzimología , Endotelio Vascular/crecimiento & desarrollo , Animales , Capilares/citología , Catepsinas/genética , Adhesión Celular , Movimiento Celular , Células Cultivadas , Colágeno/metabolismo , Elastina/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/fisiología , Humanos , Ratones , Ratones Noqueados , Cicatrización de HeridasRESUMEN
This study investigated interactions between SRY, the Y chromosome encoded male sex determining factor, and the androgen receptor (AR). Coexpression of AR and SRY caused marked repression of AR transcriptional activity on a series of androgen-responsive reporter genes. Mammalian one- and two-hybrid experiments demonstrated an AR-SRY interaction mediated by the AR DNA binding domain. Precipitations with glutathione S-transferase fusion proteins indicated that AR-SRY interactions were direct and mediated by the AR DNA binding domain and the SRY high mobility group box DNA binding domain. Transient expression of SRY in LNCaP prostate cancer cells repressed expression of an androgen-dependent prostate-specific antigen (PSA) reporter gene and stable SRY expression repressed the endogenous PSA gene. SRY protein expression was increased by proteosome inhibitors and by the androgen-liganded AR in transient and stable transfectants. AR transcriptional activity was also repressed by DAX1, and the effects of SRY and DAX1 on the AR were additive. These findings indicate that interactions between the AR, SRY, and DAX1 contribute to normal male development and function and suggest a general role for protein-protein interactions between high mobility group box proteins and steroid hormone receptors in regulating tissue-specific gene expression.
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Proteínas de Unión al ADN/fisiología , Proteínas Nucleares , Receptores Androgénicos/fisiología , Proteínas Represoras , Procesos de Determinación del Sexo , Transcripción Genética/fisiología , Secuencia de Bases , Línea Celular , Receptor Nuclear Huérfano DAX-1 , Cartilla de ADN , Proteínas de Unión al ADN/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Humanos , Hidrólisis , Masculino , Antígeno Prostático Específico/genética , Neoplasias de la Próstata/inmunología , Receptores Androgénicos/metabolismo , Receptores de Ácido Retinoico/fisiología , Proteína de la Región Y Determinante del Sexo , Factores de Transcripción/fisiología , Técnicas del Sistema de Dos HíbridosRESUMEN
The Chinese version of the Davidson Trauma Scale (DTS-C) was developed to respond to the need of Chinese-speaking individuals. The DTS is a validated self-rating scale used in the diagnosis of posttraumatic stress disorder (PTSD). The DTS-C is translated from DTS through a two-stage translation. Subjects were drawn from a sample of 210 survivors of the 21 September 1999, Chi-Chi Earthquake. The scale showed good internal consistency (Cronbach's alpha = 0.97) and test-retest reliability (r = 0.88). Concurrent validity was obtained against the clinical diagnostic interview, with a diagnostic accuracy of 0.85 at DTS-C score of 44. It showed that the sensitivity was 0.9, specificity 0.81, positive likelihood ratio 4.74, and negative likelihood ratio 0.12. The recommended stratum-specific likelihood ratios were 0.10 (95% CI: 0.05-0.20) for the score range 0-39, 4 (2.22-7.23) for the score range of 40-59, and 6.14 (3.42-11.02) for the scores above 60. In PTSD diagnosed subjects, the factor structures closely resembled the DSM-IV grouping of PTSD symptoms. The psychometric strength of DTS-C is reliable for its future use, particularly for screening for subjects with possible diagnosis of PTSD.
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Comparación Transcultural , Desastres , Inventario de Personalidad/estadística & datos numéricos , Trastornos por Estrés Postraumático/diagnóstico , Sobrevivientes/psicología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Trastornos por Estrés Postraumático/etnología , Trastornos por Estrés Postraumático/psicología , TaiwánRESUMEN
OBJECTIVES: In a population-based case-control study in Yangzhong, China, we investigated the relationship between genetic polymorphisms of GSTP1 and susceptibility to gastric cancer and its premalignant lesion, chronic gastritis. The possible gene-gene interactions between GSTP1 polymorphisms and GSTM1, GSTT1 genes were explored. METHODS: Epidemiologic data were collected by standard questionnaire from 133 gastric cancer cases, 166 chronic gastritis cases, and 433 cancer-free population controls. Blood samples for Helicobacter pylori and molecular marker assays were collected from 84 gastric cancer cases, 146 chronic gastritis, and 429 population controls. GSTP1 polymorphisms were determined by the PCR-RFLP method and H. pylori infection was measured by the ELISA method. Associations between certain GSTP1 genotypes and both gastric cancer and chronic gastritis were assessed by odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression. RESULTS: The distributions of three GSTP1 genotypes, Ile/Ile, Ile/Val, and Val/Val, were similar in gastric cancer cases, chronic gastritis, and controls. After adjusting for age, gender, education, body mass index, pack-year of smoking, alcohol drinking, H. pylori infection, salt and fruit intakes, the adjusted ORs of Val/Val were 1.3 (95% CI: 0.1-11.2) for gastric cancer and 0.9 (95% CI: 0.2-4.8) for chronic gastritis. Combining the Val alleles (Val/Val and Ile/Val) into one group, no association was observed between GSTP1 and both gastric cancer and chronic gastritis. In addition, the allelism at the GSTP1 locus did not increase gastric cancer and chronic gastritis risks associated with the GSTM1 or GSTT1 genotypes. CONCLUSION: Our data suggest that the GSTP1 genotype seems not to be associated with the risk of gastric cancer and chronic gastritis in a high-risk Chinese population.
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Glutatión Transferasa/genética , Isoenzimas/genética , Polimorfismo Genético/genética , Neoplasias Gástricas/genética , Adulto , Estudios de Casos y Controles , China , Enfermedad Crónica , Femenino , Gutatión-S-Transferasa pi , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/inmunología , Humanos , Modelos Logísticos , Masculino , Oportunidad Relativa , Prevalencia , Factores de RiesgoAsunto(s)
Trastornos Neurocognitivos/diagnóstico , Papiloma del Plexo Coroideo/cirugía , Complicaciones Posoperatorias/diagnóstico , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Adulto , Atrofia , Cerebelo/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Trastornos Neurocognitivos/psicología , Complicaciones Posoperatorias/psicologíaRESUMEN
Despite the declining trend, stomach cancer remains the second most common cancer worldwide. We examined the role of green tea consumption on chronic gastritis and stomach cancer risks. A population-based case-control study was conducted in Yangzhong, China, with 133 stomach cancer cases, 166 chronic gastritis cases, and 433 healthy controls. Epidemiologic data were collected by standard questionnaire and odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models in SAS. Inverse association was observed between green tea drinking and chronic gastritis and stomach cancer risks. After adjusting for age, gender, education, body mass index, pack-years of smoking and alcohol drinking, ORs of green tea drinking were 0.52 (95% CI: 0.29-0.94) and 0.49 (95% CI: 0.31-0.77) for stomach cancer and chronic gastritis, respectively. In addition, dose-response relationships were observed with years of green tea drinking in both diseases. The results provide further support on the protective effect of green tea against stomach cancer. This is the first time that green tea drinking was found to be protective against chronic gastritis, which may be of importance when designing intervention strategies for stomach cancer and its pre-malignant lesions in the high-risk population.
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Gastritis/prevención & control , Fitoterapia , Neoplasias Gástricas/prevención & control , Té/uso terapéutico , Adulto , Factores de Edad , Consumo de Bebidas Alcohólicas , Estudios de Casos y Controles , Relación Dosis-Respuesta a Droga , Femenino , Gastritis/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Análisis de Regresión , Factores de Riesgo , Factores Sexuales , Fumar , Neoplasias Gástricas/epidemiologíaRESUMEN
Androgen receptor (AR) belongs to the steroid hormone nuclear receptor superfamily. It functions as an androgen-dependent transcriptional factor that regulates genes for cell proliferation and differentiation. Caveolin is a principal component of caveolae membranes serving as a scaffold protein of many signal transduction pathways. Recent results correlate caveolin-1 expression with androgen sensitivity in murine prostate cancer. Furthermore, immunohistochemical staining of patient specimens suggests that caveolin expression may be an independent predictor of progression of prostate cancer. In this study, we investigate the potential interactions between AR signaling and caveolin-1 and demonstrate that overexpression of caveolin-1 potentiates ligand-dependent AR activation. Conversely, down-regulation of caveolin-1 expression by a caveolin-1 antisense expression construct can down-regulate ligand-dependent AR activation. Association between these two molecules is also demonstrated by co-localization of AR with caveolin-rich, low-density membrane fractions isolated by an equilibrium sucrose gradient centrifugation method. Co-immunoprecipitation and glutathione S-transferase fusion protein pull-down experiments demonstrate that interaction between AR and caveolin-1 is an androgen-dependent process, offering further evidence for a physiological role of this interaction. Using a mammalian two-hybrid assay system, we determine that the NH(2) terminus region of caveolin-1 is responsible for the interaction with both the NH(2)-terminal domain and the ligand-binding domain of AR.