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1.
J Econ Entomol ; 106(6): 2548-56, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24498757

RESUMEN

The Asian corn borer, Ostrinia furnacalis (GuenCe), is a major pest of maize in China. Transgenic Bt maize could provide an effective way to control this pest. However, the potential of resistance evolution has been documented in the laboratory-a CrylAb-resistant strain of Asian corn borer (Asian corn borer-AbR) could survive well on two Bt maize events, that is, MON810 and Bt11. Pyramided transgenic crops with multiple dissimilar Bt insecticidal proteins offer a superior route for pests control compared with that with one Bt single gene. In this study, two novel transgenic Bt maize events (N30 and V3), which contained a fused gene Cry1Ab/Cry2Aj and CrylAb /Vip3DA, respectively, were evaluated for their efficacy on protection against CrylAb-susceptible Asian corn borer (Asian corn borer-BtS) as well as their potential for dealing with the Asian corn borer-AbR. In laboratory bioassay, no neonate larvae of Asian corn borer-BtS fed on the whorl leaves, tassels, husks, silks, and kernels of N30 and V3 could survive at 96 h after infestation. In contrast, only 2.0-8.7% larvae died as they fed on non-Bt maize tissues. As Asian corn borer-AbR neonate larvae fed on N30 and V3 silks and kernels, 95.0% even more larvae were killed at 96 h after infestation, and all died at 168 h after infestation, while 10.0-11.67% larvae survived on non-Bt control. In the field test under artificial infestation at middle whorl leaf and silking stages of maize, there were no significant leaf, silk, and stalk damage on Bt maize plants by comparison with severe leaf feeding, stalk born, and ear damage in control, in addition, the expression profiles of a fused protein of CrylAb/Cry2Aj or CrylAb/Vip3DA in different tissues of N30 and V3 were also confirmed. In conclusion, it is clear that both Bt maize events (N30 and V3) show great potential for protecting maize from attack by Asian corn borer that has resistance to Cry1Ab protein.


Asunto(s)
Bacillus thuringiensis/genética , Proteínas Bacterianas/genética , Endotoxinas/genética , Proteínas Hemolisinas/genética , Resistencia a los Insecticidas , Insecticidas/farmacología , Mariposas Nocturnas/efectos de los fármacos , Zea mays/genética , Animales , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/metabolismo , Endotoxinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Proteínas Hemolisinas/metabolismo , Larva/efectos de los fármacos , Control Biológico de Vectores , Plantas Modificadas Genéticamente/genética , Pupa/efectos de los fármacos
2.
Environ Sci Process Impacts ; 22(8): 1718-1730, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32672296

RESUMEN

Heavy metal pollution in fine particulate matter (PM2.5) is a serious environmental and health concern in China, particularly during winter. Here, we detected 40 elements in 24 h integrated daily PM2.5 samples collected in January 2014 from three typical Chinese metropolises (Beijing, Changchun, and Chengdu) to reflect elemental spatial variations, local sources, and regional transport. The measured elemental concentrations in Changchun were 11.1% and 48.4% higher than those in Beijing and Chengdu, respectively. Thus, PM2.5 from Changchun exhibited high levels and diversity in the elemental profile (characterized by high concentrations of industrial emission elemental markers). The results of elemental ratios and Pb isotopes proved that, except for a coal combustion source, vehicular emissions contributed more to PM2.5 heavy metals in Beijing than in the other two cities; Changchun PM2.5 elements received large contributions from industrial sources, including iron and steel manufacturing, and automobile industry. Moreover, crustal dust from long-range transport of regional air masses from the northwest regions of China played a crucial role in determining elemental levels in Beijing and Changchun, accounting for more than 50% of source intensity. However, a specific dominant source was not determined in Chengdu; the contribution of anthropogenic dust, mainly from construction activities, needs to be paid attention in Chengdu eastern area. This study contributed to enhancing our understanding of elemental spatial distribution characteristics and sources and to setting more judicious standards and strategies for PM2.5 bound heavy metals in China.


Asunto(s)
Contaminantes Atmosféricos , Plomo , Beijing , China , Ciudades , Polvo , Monitoreo del Ambiente , Isótopos , Material Particulado , Estaciones del Año
3.
Sheng Li Xue Bao ; 52(4): 301-4, 2000 Aug.
Artículo en Zh | MEDLINE | ID: mdl-11951111

RESUMEN

The effect of intracoronary radiation on extracellular signal regulated kinase 1/2 (ERK1/2) activity and c-fos mRNA after coronary artery balloon injury was investigated in swine. Twenty three swines were randomly divided into a radiation group and a control group after coronary balloon over stretch. The dilated segments in the radiation group were exposed to a dose of 20 Gy by a catheter based radiation system. The animals were sacrificed at 3 (6 swines from each group) and 30 days (6 swines from radiation group and 5 from control group) after the operation. The injured segments were processed to examine c-fos gene expression by reverse transcription polymerase chain reaction (RT PCR) and to measure the activity of ERK1/2 biochemically. Intracoronary radiation decreased significantly the ERK1/2 activity and gene expression of c-fos in the radiation treated animals 3 days after coronary balloon injury (20.5%,P<0.01; 47.7%,P<0.05), but neither ERK1/2 activity nor c-fos gene expression was significantly affected by endovascular radiation in animals 30 days after balloon injury. Therefore, both ERK1/2 and c-fos may be involved in inhibiting restenosis.


Asunto(s)
Braquiterapia/métodos , Reestenosis Coronaria/radioterapia , Proteínas Quinasas Activadas por Mitógenos/biosíntesis , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Angioplastia Coronaria con Balón/efectos adversos , Animales , Terapia Combinada , Reestenosis Coronaria/prevención & control , Femenino , Radioisótopos de Iridio/administración & dosificación , Masculino , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Proto-Oncogénicas c-fos/genética , ARN Mensajero/biosíntesis , Distribución Aleatoria , Porcinos Enanos
4.
Sheng Li Xue Bao ; 50(5): 539-42, 1998 Oct.
Artículo en Zh | MEDLINE | ID: mdl-11367750

RESUMEN

Mitogen-activated protein kinases (MAPKs) are thought to be critical components in signal transduction pathways in regulation of cell growth and differentiation. The purpose of the present investigation is to study possible involvement of MAPKs in the progress of cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and effects of age on Angiotensin II (Ang II), MAPK activity and cardiac hypertrophy. The animals were divided into three groups: 4 months old WKY rats (n = 8), 4 month old SHRs (n = 8) and 15 month old SHRs (n = 6). Ratio of heart to body weight was measured. Ang II was determined by RIA. MAPK activity in cardiac tissue was assayed by the "in-gel" myelin basic protein phosphorylation. The results show that in comparison with 4 month old WKY rats, Ang II in plasma and cardiac tissues were elevated (216.4%, P < 0.01; 101.2%, P < 0.01) in 4 months old SHRs, while the MAPK activity was increased 107.0% (P < 0.01) with a parallel cardiac hypertrophy (P < 0.01). In comparison with 4 month old SHRs, Ang II and MAPK activity in cardiac tissue of the 15 months old SHRs were decreased (31.3%, P < 0.01; 29.7%, P < 0.05) but the cardiac hypertrophy increased by 38.5% (P < 0.01). MAPK may be involved in the progress of cardiac hypetrophy in SHR and the increased MAPK activity may be partly induced by Ang II.


Asunto(s)
Angiotensina II/metabolismo , Cardiomegalia/metabolismo , Hipertensión/fisiopatología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Miocardio/metabolismo , Animales , Cardiomegalia/etiología , Hipertensión/complicaciones , Técnicas In Vitro , Masculino , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY
5.
Zhonghua Yi Xue Za Zhi ; 79(1): 34-7, 1999 Jan.
Artículo en Zh | MEDLINE | ID: mdl-11601004

RESUMEN

OBJECTIVE: To study the genomic abnormality underlying the blast crisis of chronic myeloid leukemia(CML). METHODS: 15 CML patients in blast crisis (BC), 3 in accelerated phase (AP) and 20 in chronic phase (CP) were analyzed by conventional cytogentics, comparative genomic hybridization (CGH) and dual color chromosomal painting. RESULTS: Philadelphia (Ph) chromosome was identified in every case studied. Only 5 among 20 CP patients had additional abnormalities while 12 out of 14 patients with disease progression (BC + AP) showed extra numerical and/or structural chromosmal aberrations. Cytogenetically, the most common chromosome gains during BC and AP were double or triple Ph chromosome(5/14), trisomy 8(5/14), trisomy 7(1/14) and 17 (1/14). Three cases showed the same region being involved in translocations t(1;17)(q12-21;q10), t(1;10) (q12-21;q26) and t(1;11)(q12-21;p15). CGH analysis detected genetic imbalances in 8 cases. In one case, a very complex chromosmal translocation del(3), del(6)(q13-21), der(6)t(17;3;6), der(17)t(6;17) was characterized by chromosomal painting. CONCLUSION: We find that the combined use of CGH, chromosomal painting, and classic cytogenetic analysis allows a better evaluation of the genomic aberration involved in CML blastic transformation, and offers new directions for its further molecular investigation.


Asunto(s)
Crisis Blástica/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Cromosoma Filadelfia , Adulto , Anciano , Niño , Deleción Cromosómica , Cromosomas Humanos Par 17 , Cromosomas Humanos Par 20 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Translocación Genética , Trisomía
6.
Curr Med Chem ; 19(35): 6072-9, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23036152

RESUMEN

Salubrinal is a selective inhibitor of endoplasmic reticulum (ER) stress and affords remarkable protection to cardiomyocytes. By studying the structure-activity relationship (SAR) of salubrinal, it was found that modification of the quinoline ring terminus and thiourea unit could confer the compound PP1-24 with markedly enhanced cardioprotective activity (EC50 ≤ 0.3 µM) that is 50-fold more potent than salubrinal. Comparative molecular field analysis (CoMFA) was performed using the obtained biological data and resulted in a statistically significant CoMFA model with high predictive power (q2 = 0.741, r2 = 0.991).


Asunto(s)
Cinamatos/química , Relación Estructura-Actividad Cuantitativa , Tiazoles/química , Tiourea/análogos & derivados , Animales , Cardiotónicos/síntesis química , Cardiotónicos/química , Cardiotónicos/farmacología , Células Cultivadas , Cinamatos/síntesis química , Cinamatos/farmacología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Fosforilación , Ratas , Tiazoles/síntesis química , Tiazoles/farmacología , Tiourea/síntesis química , Tiourea/química , Tiourea/farmacología , eIF-2 Quinasa/metabolismo
7.
Phys Rev Lett ; 101(10): 102004, 2008 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-18851209

RESUMEN

We observe an obvious anomalous line shape of the e;{+}e;{-}--> hadrons total cross sections in the energy region between 3.700 and 3.872 GeV. It is inconsistent with the explanation for only one simple psi(3770) resonance with a statistical significance of 7sigma. The anomalous line shape may be explained by two possible enhancements of the inclusive hadron production near the center-of-mass energies of 3.764 and 3.779 GeV, indicating that either there is likely a new structure in addition to the psi(3770) resonance around 3.773 GeV, or there are some physics effects reflecting the DD[over ] production dynamics.

8.
Phys Rev Lett ; 100(10): 102003, 2008 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-18352176

RESUMEN

The decays of J/psi --> etaphif(0)(980)[eta --> gammagamma, phi --> K(+) K(-), f(0)(980) --> pi(+)pi(-)] are analyzed using a sample of 5.8 x 10(7) J/psi events collected with the BESII detector at the Beijing Electron-Positron Collider. A structure at around 2.18 GeV/c(2) with about 5 sigma significance is observed in the phif(0)(980) invariant mass spectrum. A fit with a Breit-Wigner function gives the peak mass and width of m = 2.186+/-0.010(stat)+/-0.006(syst) GeV/c(2) and Gamma = 0.065+/-0.023(stat)+/-0.017(syst) GeV/c(2), respectively, which are consistent with those of Y(2175), observed by the BABAR Collaboration in the initial-state radiation process e(+)e(-) --> gamma(ISR) phif(0)(980). The production branching ratio is determined to be Br(J/psi --> etaY(2175))Br(Y(2175)- -> phif(0)(980))Br(f(0)(980) --> pi(+)pi(-)) = [3.23+/-0.75(stat)+/-0.73(syst)] x 10(-4), assuming that the Y(2175) is a 1(--) state.

9.
Phys Rev Lett ; 100(19): 192001, 2008 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-18518438

RESUMEN

Using psi(2S) --> pi(+)pi(-) J/psi events in a sample of 14.0 x 10(6) psi(2S) decays collected with the BES-II detector, a search for the decay of the J/psi to invisible final states is performed. No signal is found, and an upper limit at the 90% confidence level is determined to be 1.2 x 10(-2) for the ratio B(J/psi --> invisible)/B(J/psi-->mu(+)mu(-)). This is the first search for J/psi decays to invisible final states.

10.
Phys Rev Lett ; 99(1): 011802, 2007 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-17678148

RESUMEN

Using 14 x 10(6) psi(2S) events accumulated at the BESII detector, we report first measurements of branching fractions or upper limits for psi(2S) decays into gammapp, gamma2(pi+pi-), gammaKS0K+pi-+c.c., gammaK+K-pi+pi-, gammaK*0K-pi++c.c., gammaK*0K*0, gammapi+pi-pp, gamma2(K+K-), gamma3(pi+pi-), and gamma2(pi+pi-)K+K- with the invariant mass of hadrons below 2.9 GeV/c2. We also report branching fractions of psi(2S) decays into 2(pi+pi-)pi0, omegapi+pi-, omegaf2(1270), b1+/-pi-/+, and pi02(pi+pi-)K+K-.

11.
Phys Rev Lett ; 97(26): 262001, 2006 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-17280420

RESUMEN

We report measurements of the continuum R(uds) near the center-of-mass energy of 3.70 GeV, the R[uds(c)+psi(3770)](s) and the R(had)(s) values in e(+)e(-) annihilation at 68 energy points in the energy region between 3.650 and 3.872 GeV with the BES-II detector at the BEPC Collider. We obtain the R(uds) for the continuum light hadron (containing u, d, and s quarks) production near the DD threshold to be R(uds)=2.141+/-0.025+/-0.085.

12.
Phys Rev Lett ; 97(14): 142002, 2006 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-17155241

RESUMEN

A broad peak is observed at low K+K- invariant mass in J/psi-->K+K-pi(0) decays found in a sample of 5.8x10(7) J/psi events collected with the BESII detector. The statistical significance of the broad resonance is much larger than 5sigma. A partial wave analysis shows that the J;{PC} of this structure is 1--. Its pole position is determined to be [1576(-55)(+49)(stat)-91+98(syst)] MeV/c(2)-i/2[818(-23)(+22)(stat)-133+64(syst)] MeV/c(2). These parameters are not compatible with any known meson resonances.

13.
Phys Rev Lett ; 97(20): 202002, 2006 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-17155676

RESUMEN

Using a data sample of 58 x 10(6) J/psi decays collected with the Beijing Spectrometer II detector at the Beijing Electron Positron Collider, searches for invisible decays of eta and eta' in J/psi to phi eta and phi eta' are performed. The phi signals, which are reconstructed in K+K- final states, are used to tag the eta and eta' decays. No signals are found for the invisible decays of either eta or eta', and upper limits at the 90% confidence level are determined to be 1.65 x 10(-3) for the ratio B(eta-->invisible)/B(eta --> gamma gamma) and 6.69 x 10(-2) for B(eta' --> invisible)/B(eta' --> gammagamma). These are the first searches for eta and eta' decays into invisible final states.

14.
Phys Rev Lett ; 97(12): 121801, 2006 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-17025950

RESUMEN

We measure the branching fractions for psi(3770)-->D(0)D[over ](0), D+D-, DD[over ], and non-DD[over ] to be (46.7+/-4.7+/-2.3)%, (36.9+/-3.7+/-2.8)%, (83.6+/-7.3+/-4.2)%, and (16.4+/-7.3+/-4.2)%, respectively. The resonance parameters of psi(3770) and psi(2S) are measured to be M_(psi(3770))=3772.2+/-0.7+/-0.3 MeV, Gamma_(psi(3770))(tot)=26.9+/-2.4+/-0.3 MeV, and Gamma_(psi(3770))(ee)=251+/-26+/-11 eV; M_(psi(2S))=3685.5+/-0.0+/-0.3 MeV, Gamma_(psi(2S))(tot)=331+/-58+/-2 keV, and Gamma_(psi(2S))(ee)=2.330+/-0.036+/-0.110 keV. We also measure the light hadron R value to be R(uds)=2.262+/-0.054+/-0.109 in the energy region from 3.660 to 3.872 GeV.

15.
Phys Rev Lett ; 97(6): 062001, 2006 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-17026161

RESUMEN

The decay J/psi-->NNpi provides an effective isospin 1/2 filter for the piN system due to isospin conservation. Using 58x10(6) J/psi decays collected with the Beijing Electromagnetic Spectrometer at the Beijing Electron Positron Collider, more than 100 thousand J/psi-->ppi-n+c.c. events are obtained. Besides the two well-known N* peaks at around 1500 MeV/c2 and 1670 MeV/c2, there are two new, clear N* peaks in the ppi invariant mass spectrum around 1360 MeV/c2 and 2030 MeV/c2 with statistical significance of 11sigma and 13sigma, respectively. We identify these as the first direct observation of the N*(1440) peak and a long-sought missing N* peak above 2 GeV/c2 in the piN invariant mass spectrum.

16.
Phys Rev Lett ; 96(16): 162002, 2006 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-16712215

RESUMEN

An enhancement near threshold is observed in the omega(phi) invariant mass spectrum from the doubly Okubo-Zweig-Iizuka-suppressed decays of J/psi-->gamma(omega)phi, based on a sample of 5.8 x 10(7) J/psi events collected with the BESII detector. A partial wave analysis shows that this enhancement favors JP=0+, and its mass and width are M=1812(+19)(-26)(stat)+/-18(syst) MeV/c2 and Gamma=105+/-20(stat)+/-28(syst) MeV/c2. The product branching fraction is determined to be B(J/psi-->gammaX)B(X-->omega(phi))=[2.61+/-0.27(stat)+/-0.65(syst)]x10(-4).

17.
Phys Rev Lett ; 95(26): 262001, 2005 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-16486345

RESUMEN

The decay channel J/psi --> gamma(pi)(+)pi(-)eta is analyzed using a sample of 5.8 x 10(7) J/psi events collected with the BESII detector. A resonance, the Chi(1835), is observed in the pi(+)pi(-)eta invariant-mass spectrum with a statistical significance of 7.7 sigma. A fit with a Breit-Wigner function yields a mass M = 1833.7 +/- 6.1(stat) +/- 2.7(syst) MeV/c(2), a width Tau = 67.7 +/- 20.3(stat) +/- 7.7(syst) MeV/c(2), and a product branching fraction B(J/psi --> gammaChi) . B(Chi --> pi(+)pi(-)eta) = [2.2 +/- 0.4(stat) +/- 0.4(syst)] x 10(-4). The mass and width of the Chi(1835) are not compatible with any known meson resonance. Its properties are consistent with expectations for the state that produces the strong pp mass threshold enhancement observed in the J/psi --> gammapp process at BESII.

18.
J Interv Cardiol ; 17(2): 87-91, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15104770

RESUMEN

OBJECTIVES: The present study assesses clinical outcomes in patients from the Potential Angina Class Improvement From Intramyocardial Channels (PACIFIC) trial of percutaneous transmyocardial revascularization (PTMR) who had previously been considered "no-option," but who subsequently underwent percutaneous coronary intervention (PCI) for continuing symptoms. BACKGROUND: Patients with advanced symptomatic coronary artery disease who are not candidates for coronary artery bypass grafting (CABG) or PCI comprise an important group, for which no established treatment is currently available. These patients have been described as having "no option," and are currently targeted for various experimental therapies. One such proposed therapy, PTMR, was recently examined in the PACIFIC trial. A subgroup of patients in this trial subsequently underwent PCI, although to initially qualify for the study they had previously been considered as unsuitable for PCI and as having "no option." The therapeutic benefit of PCI for patients of this type is unknown. METHODS: A retrospective analysis was performed on data obtained from all subjects of the PACIFIC study who underwent PCI within the 12-month follow-up period. RESULTS: Ten subjects originally randomized to PTMR and 11 subjects from the medical treatment group underwent PCI. Most had undergone at least one prior PCI and at least one CABG, and there was a high prevalence of cardiovascular risk factors. Despite excellent immediate procedural success, PCI resulted in only modest, statistically nonsignificant increases in mean exercise duration, small improvements in angina status, and no significant improvements in quality of life. CONCLUSIONS: These data suggest that PCI provides only marginal-if any-symptomatic benefit in these patients.


Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad Coronaria/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Resultado del Tratamiento
19.
Breast Cancer Res ; 3(4): 253-63, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11434876

RESUMEN

BACKGROUND: Chemotherapy is important in the systematic treatment of breast cancer. To enhance the response of tumours to chemotherapy, attention has been focused on agents to reverse multidrug resistance (MDR) and on the sensitivity of tumour cells to chemical drugs. Hundreds of reversal drugs have been found in vitro, but their clinical application has been limited because of their toxicity. The reversal activity of progestogen compounds has been demonstrated. However, classical agents such as progesterone and megestrol (MG) also have high toxicity. Nomegestrol (NOM) belongs to a new derivation of progestogens and shows very low toxicity. We studied the reversal activity of NOM and compared it with that of verapamil (VRP), droloxifene (DRO), tamoxifen (TAM) and MG, and investigated the reversal mechanism, i.e. effects on the expression of the MDR1, glutathione S-transferase Pi (GSTpi), MDR-related protein (MRP) and topoisomerase IIalpha (TopoIIalpha) genes, as well as the intracellular drug concentration and the cell cycle. The aim of the study was to examine the reversal effects of NOM on MDR in MCF7/ADR, an MCF7 breast cancer cell line resistant to adriamycin (ADR), and its mechanism of action. METHODS: MCF7/ADR cells and MCF7/WT, an MCF7 breast cancer cell line sensitive to ADR, were treated with NOM as the acetate ester. With an assay based on a tetrazolium dye [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide; MTT], the effects of various concentrations of NOM on MDR in MCF7/ADR cells were studied. Before and after the treatment with 5 microM NOM, the expression of the MDR-related genes MDR1, GSTpi, TopoIIalpha and MRP were assayed with a reverse transcriptase polymerase chain reaction (RT-PCR) immunocytochemistry assay. By using flow cytometry (FCM), we observed the intracellular ADR concentration and the effects of combined treatment with NOM and ADR on the cell cycle. Results collected were analysed with Student's t test. RESULTS: NOM significantly reversed MDR in MCF7/ADR cells. After treatment NOM at 20, 10 and 5 microM, chemosensitivity to ADR increased 21-fold, 12-fold and 8-fold, respectively. The reversal activity of NOM was stronger than that of the precursor compound MG, and comparable to that of VRP. After treatment with 5 microM NOM, the expression of both the MDR1 and the GSTpi mRNA genes began to decline on the second day (P <0.05 and P <0.01, respectively), and reached the lowest level on the third day (both P <0.01); however, on the fifth day the expression levels began to increase again (both P <0.05). The expression of MRP and TopoIIalpha had no significant changes. Changes in the expression of P-glycoprotein (P-gp) and GSTpi were similar to those of their mRNA expressions, showing early declines and late increases. Two hours after treatment with 20, 10 and 5 microM NOM, the intracellular ADR concentration increased 2.7-fold, 2.3-fold and 1.5-fold respectively. However, NOM did not increase ADR accumulation in MCF7/WT cells. FCM data showed that after 48 h of combined administration of NOM (20 microM) and ADR (from low to high concentration), MCF7/ADR cells showed a gradual arrest at the G2M phase with increasing ADR dose. The arrest effect with combined drug treatment was stronger than that with the single ADR treatment. CONCLUSION: MDR is the major mechanism of drug resistance in malignant tumour cells. To overcome MDR and to increase chemosensitivity, many reversal agents have been found. Most progestogen compounds have been demonstrated to have reversal effects, but we found no data on NOM, a new progestogen compound. Our results show that NOM has strong reversal activity. The reversal effects were stronger than those of the precursor compound, MG, and were comparable to that of VRP. Because NOM has low toxicity, it might have good prospects in clinical application. Using RT-PCR and immunocytochemistry assays, we studied the effects of NOM on MDR-related genes. The results were that NOM could markedly downregulate the mRNA and protein expression levels of MDR1 and GSTpi. TopoIIalpha and MRP gene expression showed no significant changes. It is known that P-gp induces MDR in tumour cells mainly by decreasing the intracellular drug concentration. After treatment with NOM, the intracellular drug concentration in MCF7/ADR cells increased significantly. Combined treatment with NOM and ADR induced arrest at the G2M phase. It is worth noting that NOM caused an early decrease and a late increase in the expression of some MDR-related genes in a time-dependent manner. The phenomena raise a question for the continued administration of reversal agents in clinics that merits further study. We demonstrate that NOM has strong reversal effects on MDR in MCF7/ADR cells. The reversal is via different routes, namely downregulating the mRNA and protein expression levels of MDR1 and GSTpi, increasing intracellular drug concentration and arresting cells at the G2M phase (NOM in combination with ADR). The reversal mechanism needs further study.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/patología , Doxorrubicina/farmacología , Resistencia a Múltiples Medicamentos , Regulación Neoplásica de la Expresión Génica , Megestrol , Norpregnadienos/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Antineoplásicos/farmacocinética , Ciclo Celular/efectos de los fármacos , ADN-Topoisomerasas de Tipo II/biosíntesis , Doxorrubicina/farmacocinética , Resistencia a Antineoplásicos , Femenino , Glutatión Transferasa/biosíntesis , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas/efectos de los fármacos
20.
J Biol Chem ; 274(50): 35741-8, 1999 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-10585455

RESUMEN

To clone zinc finger genes expressed in hematopoietic system, we designed primers based on conserved Cys(2)/His(2) zinc finger sequences to amplify corresponding domains from mRNA of normal bone marrow and leukemia cell line NB4. DNA fragments of novel zinc finger genes were chosen and used as probe pool to screen cDNA libraries or subject to rapid amplification of cDNA ends in order to obtain full-length cDNA. Six cDNAs including whole open reading frame of zinc finger proteins, named as ZNF191, ZNF253 (BMZF-1), ZNF255 (BMZF-2), ZNF256 (BMZF-3), ZNF257 (BMZF-4), and ZNF254 (BMZF-5) were obtained. All six belong to the Krüppel-like zinc finger gene family, and typical transcriptional regulatory motifs exist in the N-terminal moiety, such as the SCAN box in ZNF191, and the KRAB domains in ZNF253, ZNF254, ZNF256, and ZNF257. A previously undefined sequence nominated as Krüppel-related novel box, which may represent a new transregulatory motif, was revealed at the N terminus of ZNF255. The transregulatory function of non-zinc finger regions of ZNF191, ZNF253, and ZNF255 were addressed in yeast and mammalian cells. The results indicated that ZNF255 might be a conditional transactivator, whereas ZNF253 and ZNF191 displayed a suppressive effect on the transcription in yeast and/or mammalian systems.


Asunto(s)
Células Madre Hematopoyéticas/metabolismo , Dedos de Zinc/genética , Secuencia de Aminoácidos , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Células Cultivadas , Clonación Molecular , ADN Complementario , Evolución Molecular , Sangre Fetal , Células Madre Hematopoyéticas/citología , Humanos , Leucemia Promielocítica Aguda , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Especificidad de Órganos , Filogenia , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Células Tumorales Cultivadas
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