RESUMEN
Metal-free ultralong organic phosphorescence (UOP) materials have attracted significant attention owing to their anomalous photophysical properties and potential applications in various fields. Here, three pyrimidine-based organic luminogens, 9-(pyrimidin-2-yl)-9H-carbazole, 9-(4,6-dimethylpyrimidin-2-yl)-9H-carbazole, and 9-(5-bromopyrimidin-2-yl)-9H-carbazole are designed and synthesized, which show efficient yellow UOP with the longest lifetimes up to 1.37 s and the highest absolute phosphorescence quantum yields up to 23.6% under ambient conditions. Theoretical calculations, crystal structures, and photophysical properties of these compounds reveal that intramolecular hydrogen bonding, intermolecular π-π interactions, and intermolecular electronic coupling are responsible for forming dimers and generating highly efficient UOP. Their efficacy as solid materials for data encryption is demonstrated.
RESUMEN
Room-temperature phosphorescence (RTP) was realized for the first time in a polyoxometalate-based charge-transfer (CT) hybrid material bearing polyoxometalates (POMs) as electron-donors (D) and rigid naphthalene diimides (NDIs) as electron-acceptors (A), meanwhile, this hybrid material displayed photochromism as well. The significant D-A anion-π interaction induced an additional through-space charge-transfer pathway. The resulting suitable D-A CT states can efficiently bridge the relatively large energy gap between the NDI-localized 1 π-π* and 3 π-π* states and thus trigger the ligand-localized phosphorescence (3 π-π*).
RESUMEN
Two efficient blue thermally activated delayed fluorescence compounds, B-oCz and B-oTC, composed of ortho-donor (D)-acceptor (A) arrangement were designed and synthesized. The significant intramolecular D-A interactions induce a combined charge transfer pathway and thus achieve small ΔEST and high efficiencies. The concentration quenching can be effectively inhibited in films of these compounds. The blue non-doped organic light emitting diodes (OLEDs) based on B-oTC prepared from solution processes shows record-high external quantum efficiency (EQE) of 19.1 %.
RESUMEN
Two mononuclear cuprous complexes [Cu(PNNA)(POP)]BF4 (1) and [Cu(PNNA)(Xantphos)]BF4 (2) (PNNA = 9,9-dimethyl-10-(6-(3-phenyl-1H-pyrazol-1-yl)pyridin-3-yl)-9,10-dihydroacridine, POP = bis[2-(dipenylphosphino)phenyl]ether, Xantphos =4,5-bis(diphenylphosphino)-9,9-dimethylxanthene), with intense bluish-green luminescence based on a new diimine ligand were designed and synthesized. Their structural, electrochemical, and photophysical properties were characterized by single-crystal X-ray analysis, cyclic voltammetry, temperature dependence of spectroscopy, time-dependent emission spectroscopy, etc. The complexes exhibit high photoluminescence quantum yields in doped films (up to 74.6%) at room temperature. Thermally activated delayed fluorescence based on intraligand charge transfer was observed by grafting a strong electron-donor moiety, 9,9-dimethylacridan, on the diimine ligand, which is supported by the density functional theory calculations on two complexes. Highly efficient solution-processed OLEDs based on these two complexes were fabricated, among which the electroluminescent device using 2 as dopant shows a peak external quantum efficiency of 7.42%, a peak current efficiency of 20.24 cd/A, and a maximum brightness of 5579 cd/m(2).
RESUMEN
Recent studies have revealed that microRNA-29c (miR-29c) is involved in a variety of biological processes including carcinogenesis. Here, we report that miR-29c was significantly downregulated in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) cell lines as well as in clinical tissues compared with their corresponding controls. Tumor necrosis factor alpha-induced protein 3 (TNFAIP3), a key regulator in inflammation and immunity, was found to be inversely correlated with miR-29c levels and was identified as a target of miR-29c. Overexpression of miR-29c in HepG2.2.15 cells effectively suppressed TNFAIP3 expression and HBV DNA replication as well as inhibited cell proliferation and induced apoptosis. We conclude that miR-29c may play an important role as a tumor suppressive microRNA in the development and progression of HBV-related HCC by targeting TNFAIP3. Thus miR-29c and TNFAIP3 represent key diagnostic markers and potential therapeutic targets for the prevention and treatment of HBV infection.
Asunto(s)
Carcinoma Hepatocelular/virología , Regulación Neoplásica de la Expresión Génica , Virus de la Hepatitis B , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Hepáticas/virología , MicroARNs/biosíntesis , Proteínas Nucleares/genética , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica/genética , Proteínas de Unión al ADN , Regulación hacia Abajo , Antígenos de Superficie de la Hepatitis B/metabolismo , Antígenos e de la Hepatitis B/metabolismo , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Virus de la Hepatitis B/fisiología , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Transfección , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfaRESUMEN
A novel cuprous complex bearing two functional parts, i.e. a luminophoric part and a structural part, exhibits distinct luminescence responses to a variety of volatile organic compounds of different polarities in the solid state.
RESUMEN
Two emissive copper(i) halide complexes (PNNP)Cu2Br2 (1) and (PNNP)Cu2I2 (2), which are constructed from butterfly-shaped dinuclear Cu2X2 cores and a new tetradentate ligand (PNNP = 1,3-bis(1-(2-(diphenylphosphanyl)phenyl)-1H-pyrazol-3-yl)benzene), were synthesized and characterized. These chelates exhibit bright green (λmax = 517 nm, 1) and bluish-green (λmax = 492 nm, 2) photoluminescence in the solid state with quantum yields of 42% (1) and 58% (2), and lifetimes of 13 µs (1) and 8.8 µs (2) at room temperature. Computational density functional theory/time-dependent density functional theory (DFT/TDDFT) calculations were performed to elucidate the nature of their electronic transitions and to predict their detailed photophysical properties. The results of DFT/TDDFT calculations, combined with the temperature dependence of spectroscopic properties and emission decay behaviors, suggest that the emission in the solid state originates from the 1,3(MLCT + XLCT + ILCT) excited states, which are in thermal equilibrium with small energy differences of about 0.1 eV. A comparative study of the titled complexes reveals that the emissive-state characteristics and photophysical properties of these complexes are significantly affected by the ligand field strength and atomic number of the halogen atom, as well as by the percentage of the XLCT transition involved in the lowest excited states. Compared with its bromide counterpart (1), the iodide complex (2) shows a much higher phosphorescence quantum yield (0.94 vs. 0.50), a much shorter phosphorescence decay time (58 µs vs. 274 µs), a much larger phosphorescence rate constant (1.6 × 104 s-1vs. 1.8 × 103 s-1), and a larger phosphorescence contribution (25% vs. 8%) in room-temperature emission, due to the more efficient spin-orbit coupling (SOC).
RESUMEN
Human gastric epithelial immortalized GES-1 cells were infected with spiral and coccoid Helicobacter pylori. Scanning electron microscopy was used to determine the ability of the two forms of H. pylori to adhere to GES-1 cells. GES-1 cell apoptosis induced by coccoid and spiral H. pylori was analysed using flow cytometry. A cDNA microarray for 22,000 human genes was used to identify the gene-expression differences in GES-1 cells infected with the two forms of H. pylori, and the gene expression identified by the cDNA microarray was confirmed by RT-PCR. Scanning electron microscope observation showed that both coccoid and spiral bacteria can adhere to GES-1 cells. After 4 h infection, apoptosis induction was 27.4% for spiral-form infection and 10.2% for coccoid-form infection. Of 268 differentially expressed genes identified by cDNA microarray, 166 showed higher expression with the spiral H. pylori infection than with the coccoid H. pylori infection. To the best of the authors' knowledge, this is the first report that GES-1 cells infected with spiral H. pylori have higher expression of cxcl10, ccl11, ccl5, groalpha, TLR5, ATF3, fos, fosl2, gadd45a and myc. The cells infected with coccoid H. pylori had higher expression of survivin. The global profile of gene expression in GES-1 cells infected with coccoid and spiral H. pylori is described for the first time.
Asunto(s)
Células Epiteliales/metabolismo , Infecciones por Helicobacter/metabolismo , Helicobacter pylori , Factor de Transcripción Activador 3/genética , Factor de Transcripción Activador 3/metabolismo , Apoptosis , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Quimiocina CCL11 , Quimiocina CCL5 , Quimiocina CXCL10 , Quimiocinas/genética , Quimiocinas/metabolismo , Quimiocinas CC/genética , Quimiocinas CC/metabolismo , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Células Epiteliales/patología , Antígeno 2 Relacionado con Fos/genética , Antígeno 2 Relacionado con Fos/metabolismo , Perfilación de la Expresión Génica , Genes fos/genética , Infecciones por Helicobacter/microbiología , Helicobacter pylori/ultraestructura , Humanos , Proteínas Inhibidoras de la Apoptosis , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Especificidad de la Especie , Estómago , Survivin , Receptor Toll-Like 5/genética , Receptor Toll-Like 5/metabolismoRESUMEN
5-Fluorouracil is the first choice chemotherapeutic drug for patients with gastric cancer, but the mechanism that 5-fluorouracil plays the anti-tumor role remains unclear. The aim of this study was to clarify correlated [corrected] proteins induced by 5-fluorouracil in the apoptosis-initiation of human gastric cancer (MGC-803) cells. The time point of apoptosis-initiation induced by 5-fluorouracil in MGC-803 cells was determinated using 5-fluorouracil-withdrawal. Two-dimensional electrophoreses (2-DE) were employed to compare the differentials of protein expressions of the MGC-803 cells at the apoptosis-initiation phase and those of the MGC-803 cells untreated with 5-fluorouracil. The differential proteins included 14 upregulated proteins and 8 downregulated proteins. They indicated a more-than-doubled alteration. These proteins were digested in gels by trypsin and the mass of generated peptides were measured by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The data obtained from peptide mass fingerprinting (PMF) were searched out using the internet available database mascot (http://www.matrixscience.com). The results showed that proteomics analyses have evidenced that many kinds of proteins are involved in the apoptosis initiation of human gastric cancer MGC-803 cells. These proteins are related to metabolism, oxidation, cytoskeleton and signal transduction and other aspects of cells. In conclusion, the experiment model of apoptosis-initiation of human gastric cancer MGC-803 cells induced by 5-fluorouracil based on proteomic analysis has been established, giving an impetus to researches of the mechanism of apoptosis in human gastric cancer, and laying a foundation for the selection of potential drug precursors specific for inducing apoptosis-initiation in human gastric cancer.
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Apoptosis/efectos de los fármacos , Fluorouracilo/farmacología , Proteómica , Neoplasias Gástricas/fisiopatología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/fisiopatología , Línea Celular Tumoral , Fluorouracilo/uso terapéutico , Humanos , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
In this communication, we report a new greenish-blue-emitting Cu(i) complex, Cu4Cl4(NP)2, a with high photoluminescence quantum yield of 90% and a short decay time of 9.9 µs. Due to the strong SOC combined with the small activation energy ΔEST, the emission at room temperature consists of approximately equivalent fast phosphorescence and TADF.
RESUMEN
Correction for 'A strongly greenish-blue-emitting Cu4Cl4 cluster with an efficient spin-orbit coupling (SOC): fast phosphorescence versus thermally activated delayed fluorescence' by Xu-Lin Chen et al., Chem. Commun., 2016, 52, 6288-6291.
RESUMEN
Multi-drug resistance (MDR) is an important factor that causes treatment failure in acute leukemia. However, the full development mechanisms of MDR still await [corrected] investigation. The purpose of this study is to investigate differentially expressed proteins in the multi-drug resistant acute myeloblastic leukemia (AML) cell line HL-60/DOX and the drug sensitive cell line HL-60, and to identify new potential multi-drug resistant related molecules with the proteomic approach. Two-dimensional gel electrophoresis (2-DE) maps of the proteins, extracted from two AML cell lines, HL-60/DOX and HL-60, were established respectively. The extracted proteins were digested by enzymes and identified with the matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The data of the peptide mass fingerprinting (PMF) was matched with databases of proteomics available on the Internet. Results showed that 16 proteins were identified to be differentially expressed between HL-60/DOX and HL-60 cells. They involved the protein disulfide isomerase precursor (PDI), the proteasomes alpha1 and other proteins which are related to drug resistance or cell metabolism, but their functional significances are required further investigation. Nevertheless, it is clear that this proteomic approach for studing the biology and development of MDR is a prerequisite in leukemia.
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Resistencia a Múltiples Medicamentos , Leucemia Mieloide Aguda/fisiopatología , Proteómica , Electroforesis en Gel Bidimensional , Células HL-60 , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Mapeo Peptídico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
OBJECTIVE: To construct the human cytomegalovirus (HCMV) pp65 DNA vaccine vector and VP22 and pp65 coexpressing vector. To evaluate and compare immunological effects in mice. METHODS: Twenty-one BALB/C mice were divided into 3 equal groups: pcDNA3.pp65 group undergoing injection of pcDNA3.pp65 as DNA vaccine, pVP22.pp65 group undergoing injection of pVP22.pp65, and control group undergoing injection of normal saline. HCMV pp65 expression vector pcDNA3.pp65, VP22 and pp65 coexpressing vector pVP22.pp65 were constructed by molecular biology methods. The vectors were immunized into BALB/C mice as DNA vaccines. The T cell proliferation activity and IL-2 biological activity were determined using MTT method. NK activity was detected using LDH release test. The serum IgM and IgG levels of HCMV, the concentrations of IL-2 and IL-4 in serum and supernatant of spleen cells were detected using ELISA method. RESULTS: The HCMV DNA vaccine expression vectors were successfully constructed. Some indexes of the two vaccine groups (pcDNA3.pp65 and pVP22.pp65), that is, T cell proliferation activity (5.11 and 5.55 for SI at 8th week respectively), NK activity (8.74% and 12.08% at 12th week respectively), IgM level (1.20 and 1.58 for A value at 6th week respectively) and IgG level (1.09 and 1.78 for A value at 6th week respectively) were higher than those of negative control, and pVP22.pp65 group was higher than pcDNA3.pp65 group (P < 0.05). The concentrations of IL-2 and IL-4 and the IL-2 biological activity were very low in sera of three groups which showed no significant difference between them (P > 0.05), but higher in the spleen supernatant and the pVP22.pp65 group was highest (411.11 pg/ml, 76.10 pg/ml for the concentrations of IL-2 and IL-4 and 0.22 for IL-2 biological activity). CONCLUSION: The HCMV pp65 could induce certain immunological activity, and VP22 could significantly enhance pp65 in vivo immunological activity.
Asunto(s)
Citomegalovirus/inmunología , Fosfoproteínas/genética , Vacunas de ADN/inmunología , Proteínas de la Matriz Viral/genética , Proteínas Estructurales Virales/genética , Vacunas Virales/inmunología , Animales , Infecciones por Citomegalovirus/prevención & control , Femenino , Vectores Genéticos , Interleucina-2/sangre , Células Asesinas Naturales/inmunología , Ratones , Ratones Endogámicos BALB C , Linfocitos T/inmunologíaRESUMEN
OBJECTIVE: To investigate the correlation between helicobacter pylori L-form (Hp-L) infection in human esophageal carcinoma (EC) and tumor angiogenesis, and study the effect of Hp-L on the malignant biological behaviors of EC. METHODS: Hp-L was examined in 98 patients with EC and 30 controls by Gram stain, electronmicroscopic technique and immunohistochemical stain (ABC method). VEGF, p53 protein and microvessel density (MVD) were examined by immunohistochemical stain (SP method) with their relationship with the clinicopathologic factors analyzed. RESULTS: The positive rate of Hp-L was 60.2% in EC group. Two types of Hp-L were detected in the tissue of EC by electronmicroscopic technique, which lay in the outer or inner carcinoma cells. The positive rates of Hp-L, MVD, VEGF and p53 in the cancer group were significantly higher than those in control group (P < 0.005-0.001). The positive rates of MVD, VEGF and p53 in the Hp-L positive group of EC were significantly higher than those in Hp-L negative group (P < 0.005-0.001). The positive rate of Hp-L was correlated with MVD (r = 0.46, P < 0.01) and the expression of VEGF and p53 (r = 0.31, P < 0.01). The positive rate of Hp-L in the EC group was correlated with vessel invasion, depth of invasion, metastasis to the para-esophageal and distant lymph nodes except tumor size. CONCLUSION: Hp-L infection in EC is closely related with tumor angiogenesis and may be an important promoting factor in esophageal carcinoma growth, invasion and metastasis.
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Neoplasias Esofágicas/complicaciones , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Neovascularización Patológica/complicaciones , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIMS AND BACKGROUND: The human life expectancy and the incidence of lung cancer have increased dramatically in recent years. As a result, there is a high demand for the management of older patients with advanced non-small cell lung cancer (NSCLC) in clinical practice. The purpose of this study is to evaluate the prognostic factors in ≥65-year-old patients with advanced NSCLC in China. METHOD: This study involved a retrospective review of 78 ≥65-year-old patients with a diagnosis of NSCLC and at an advanced stage of disease, defined as stage IIIB or IV. All patients were followed up for a 3-year interval to determine the survival rates. Clinical data including gender, smoking history, comorbidities, performance status (PS), histological differentiation, disease stage, treatment and overall survival were recorded. The log-rank test was used to calculate survival rates. Multivariate Cox regression analysis was performed to determine independent prognostic factors. RESULTS: The 1-year, 2-year and 3-year survival rates of the 78 patients were 44.9%, 23.1% and 9.0%, respectively. In univariate analysis by the log-rank test, the 3-year survival rate was significantly associated with PS (P <0.01), disease stage (P <0.01) and chemotherapy treatment (P <0.01). The results of multivariate Cox regression analysis confirmed that PS and disease stage were independent prognostic factors. CONCLUSION: The 3-year survival rate in ≥65-year-old patients with advanced NSCLC was significantly associated with PS, disease stage and chemotherapy. PS and disease stage were independent prognostic factors. Older patients with advanced NSCLC in China might benefit from chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , China/epidemiología , Femenino , Humanos , Estimación de Kaplan-Meier , Estado de Ejecución de Karnofsky , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: To study whether progestogen antagonist mifepristone could reverse multidrug resistance of K562/A02 cells and its mechanisms. METHODS: MTT was used to study the proliferation of K562/A02 cells and sensitivity of K562/A02 cells to ADM after 72 hours treatment with mifepristone. Flow cytometry was used to assay the expression of P-glycoprotein and the mean fluorescent intensity of intracellular daunorubicin. The expressions of apoptosis related proteins (bcl-2, Bax and caspase-3) were assayed by immunohistochemistry and the glucosylceramide synthase mRNA expression by RT-PCR before and after mifepristone treatment. RESULTS: MTT assay revealed that 2.5, 5.0 and 10 micromol/L mifepristone did not affect the proliferation of K562/A02 cells, but enhanced the sensitivity of K562/A02 cells to ADM, by 1. 68-, 4.17- and 10.71- fold increase, respectively. Expression of P-gp in K562/A02 cells was (49.03 +/- 5.32)%, and was decreased to (28.60 +/- 2.13)% (P < 0.01) after 10 micromol/L mifepristone treatment for 72 hours. and intracellular DNR accumulation in K562/A02 was (61.07 +/- 8.61)%, and was increased to (92.72 +/- 3.48)% (P < 0.01). After 10 micromol/L mifepristone treatment, the expression of bcl-2 protein was decreased from (56 +/- 9)% to (37 +/- 6)% (P < 0.05), Bax and caspase-3 proteins was increased from (40 +/- 5)% to (87 +/- 10)% (P < 0.01), and from (36 +/- 7)% to (89 +/- 6)% (P < 0.01) respectively. RT-PCR analysis revealed that expression of glucosylceramide synthase mRNA was higher in K562/A02 than in K562 cells, whereas 10 micromol/L mifepristone significantly down-regulated its expression in K562/A02 cells. CONCLUSION: Mifepristone at 10 micromol/L could dose-dependently reverse the multidrug resistance of K562/A02 cells. The possible mechanisms are related with decreasing the expression of P-gp, regulating the expression of apoptosis related proteins and decreasing the expression of glucosylceramide synthase.
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Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Mifepristona/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Proliferación Celular/efectos de los fármacos , Daunorrubicina/farmacocinética , Doxorrubicina/farmacología , Glucosiltransferasas/genética , Glucosiltransferasas/metabolismo , Humanos , Células K562 , ARN Mensajero/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVE: To study the maturation effect of CpG2006 and phosphodiester oligonucleotides on leukemia-derived dendritic cells. METHODS: Leukemia cells K562/A02 were induced into dendritic cells by rhGM-CSF and rhIL-4. After 7 days induction, the cell-morphology was observed, the immunophenotype of cells was detected by flow cytometry and the cell function was evaluated by allogeneic mixed lymphocyte reactions, CTL responses and secretion of IL-12 and IL-6. Then a CpG oligonucleotide CpG2006, two synthetic bacterial phosphodiester oligonucleotides A-ODN and T-ODN were added to these leukemia-derived DCs. Three days later, the DCs were re-detected by the above-mentioned methods. RESULTS: After induced by CpG2006, A-ODN or T-ODN, the leukemia-derived DCs with typical dendritic morphology were increased. The expressions of CD83, HLA-DR and CD86 were (65.5 +/- 8.4)%, (32.0 +/- 4.3)% and (18.6 +/- 3.2)% respectively in day 7 leukemia-derived DCs, raised to (88.9 +/- 3.6)%, (53.9 +/- 3.2)% and (39.9 +/- 7.3)% respectively after exposing CpG2006 for 3 days; increased to (97.0 +/- 5.3)%, (63.9 +/- 7.3)% and (40.2 +/- 7.4)% respectively after treated by A-ODN; and further increased to (93.26 +/- 4.65)%, (58.3 +/- 5.6)% and (36.2 +/- 6.8)% respectively after treated by T-ODN. These results was markedly different than unaffected cells did. These DCs induced by the above-mentioned three oligonucleotides could upregulate significantly the capacity for stimulating allogeneic T cells. They could also induce CTL to generate specific cytotoxic activity against K562/A02 cells. The secretion of IL-6 and IL-12 was increased remarkably. CONCLUSION: CpG2006, as well as two phosphodiester oligonucleotides can induce leukemia-derived DCs maturation.
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Diferenciación Celular/efectos de los fármacos , Células Dendríticas/citología , Oligonucleótidos/farmacología , Supervivencia Celular/efectos de los fármacos , Células Dendríticas/efectos de los fármacos , Humanos , Células K562 , Oligodesoxirribonucleótidos/farmacologíaRESUMEN
Although human papillomavirus (HPV) infections are the primary cause of cervical cancer, the molecular mechanism by which HPV induces cervical cancer remains largely unclear. We used two-dimensional electrophoresis with mass spectrometry to study protein expression profiling between HPV16-positive cervical mucosa epithelial H8 cells and cervical cancer Caski cells to identify 18 differentially expressed proteins. Among them, retinoblastoma-binding protein 4 (RbAp48) was selected, and its differentiation expression was verified with both additional cervical cancer-derived cell lines and human tissues of cervical intraepithelial neoplasia and cervical cancer. Suppression of RbAp48 using small interfering RNA approach in H8 cells significantly stimulated cell proliferation and colony formation and inhibited senescence-like phenotype. Remarkably, H8 cells acquired transforming activity if RpAp48 was suppressed, because H8 cells stably transfected with RbAp48 small interfering RNA led to tumor formation in nude mice. In addition, overexpression of RbAp48 significantly inhibited cell growth and tumor formation. This RbAp48-mediated transformation of HPV16 is probably because of the regulation by RbAp48 of tumor suppressors retinoblastoma and p53, apoptosis-related enzymes caspase-3 and caspase-8, and oncogenic genes, including E6, E7, cyclin D1 (CCND1), and c-MYC. In brief, RbAp48, previously unknown in cervical carcinogenesis, was isolated in a global screen and identified as a critical mediator controlling the transforming activity of HPV16 in cervical cancer.
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Proteínas Portadoras/metabolismo , Transformación Celular Viral , Regulación Neoplásica de la Expresión Génica , Papillomavirus Humano 16/metabolismo , Proteínas Nucleares/metabolismo , Displasia del Cuello del Útero/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Animales , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/genética , Caspasa 3/biosíntesis , Caspasa 3/genética , Caspasa 8/biosíntesis , Caspasa 8/genética , Línea Celular Transformada , Línea Celular Tumoral , Transformación Celular Viral/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Ciclina D , Ciclinas/biosíntesis , Ciclinas/genética , Electroforesis en Gel Bidimensional , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HeLa , Papillomavirus Humano 16/genética , Humanos , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/genética , Proteínas Oncogénicas Virales/biosíntesis , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus , Fenotipo , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Proteínas Proto-Oncogénicas c-myc/genética , ARN Interferente Pequeño/farmacología , Proteínas Represoras/biosíntesis , Proteínas Represoras/genética , Proteína de Retinoblastoma/biosíntesis , Proteína de Retinoblastoma/genética , Proteína 4 de Unión a Retinoblastoma , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genética , Neoplasias del Cuello Uterino/genética , Displasia del Cuello del Útero/genética , Displasia del Cuello del Útero/virologíaRESUMEN
OBJECTIVE: To study the related proteins of apoptosis initiation induced by homoharringtonine (HHT) in HL-60 cells. METHODS: After establishment of an apoptosis initiation model induced by HHT in HL-60 cells, proteins of untreated and HHT treated HL-60 cells were extracted, and the two-dimensional polyacrylamide gel electrophoresis (2-DE) maps of the extracted proteins were established by using the immobilized pH gradient (IPG) two-dimensional electrophoresis respectively. The alteration protein spots were identified with assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and database searching. RESULTS: Proteomics analysis showed that proteins including MHC class I antigen, calbindin D-28K, chloride channel protein 6, oncoprotein 18, zinc finger protein Helios and apoptosis inhibitor like protein 2 were involved in apoptosis initiation induced by HHT. CONCLUSION: The present study might conduce to the researches of HL-60 cells carcinogenesis and pave the way to exploit drug precursor related to HHT and initiation of apoptosis in HL-60 cells.
Asunto(s)
Apoptosis/efectos de los fármacos , Harringtoninas/farmacología , Proteínas de Microtúbulos , Proteoma/análisis , Antineoplásicos Fitogénicos/farmacología , Calbindinas , Canales de Cloruro/análisis , Proteínas de Unión al ADN/análisis , Electroforesis en Gel Bidimensional/métodos , Células HL-60 , Antígenos de Histocompatibilidad Clase I/análisis , Homoharringtonina , Humanos , Factor de Transcripción Ikaros , Proteínas Inhibidoras de la Apoptosis , Fosfoproteínas/análisis , Proteínas/análisis , Proteína G de Unión al Calcio S100/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Estatmina , Factores de Transcripción/análisisRESUMEN
OBJECTIVE: To observe the antileukemic effect of lymphocytes from cord blood treated by CpG-oligodeoxynucleotides (CpG-ODN). METHODS: Lymphocytes from cord blood were exposed to different oligodeoxynucleotides containing a panel of CpG-ODN and were cultured with K562 cells. The cytotoxic effects were detected by MTT method. Immunological markers of cord blood treated by CpG-ODN(3) which showed highest activity were measured with flow cytometry. RESULTS: Different CpG-motifs have different immunostimulatory activity and CpG-ODN(3) has the highest one. After treated by CpG-ODN(3), NK killing activity to K562 cells increased in a dose-dependent manner, and CD(3), CD(4), CD(19) and CD(56) increased to (60.6 +/- 7.9)%, (40.2 +/- 3.5)%, (22.4 +/- 1.9)% and (15.5 +/- 3.1)%, respectively. CONCLUSION: CpG-ODN could reinforces the immunological competence of cord blood lymphocytes and their effects on K562 cells. This provides a new approach to reinforce the antitumor effects of cord blood.