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1.
Science ; 380(6652): 1390-1396, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37289911

RESUMEN

Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory (LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.

2.
Phys Rev Lett ; 129(26): 261103, 2022 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-36608208

RESUMEN

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9} GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

3.
Zhonghua Xue Ye Xue Za Zhi ; 42(12): 1015-1020, 2021 Dec 14.
Artículo en Chino | MEDLINE | ID: mdl-35045673

RESUMEN

Objective: To investigate the regulatory effect of targeted siRNA on ß-globin in erythroid cells cultured by targeted differentiation in vitro and provide new theoretical support for gene therapy for hemoglobin H (HbH) disease. Methods: Based on the ß-globin gene expression results, the optimal siRNA sequence and its effective action dose were screened in erythroid cells, and the effect of the effective dose of the optimal siRNA on the regulation of ß-globin expression and apoptosis in erythroid cells was examined. The effective dose of the optimal siRNA was applied to erythroid cells with HbH disease. The effects of transfected siRNAs on red line cells with HbH disease were comprehensively evaluated by measuring the expression of ß-globin, reactive oxygen species (ROS) , and apoptosis rates. Results: Within 96 hours after transfection, siRNA2 significantly downregulated ß-globin expression in in vitro cultured erythroid cells, but not α-globin. siRNA silencing effect and duration of effect were dose-dependent. siRNA2 downregulated ß-globin expression, reduced intracellular ROS production, and decreased apoptosis rate in erythroid cells with HbH disease. Conclusion: Targeted siRNAs can downregulate ß-globin expression, reduce intracellular ROS production, and downregulate apoptosis rate in erythroid cells with HbH disease.


Asunto(s)
Talasemia alfa , Eritrocitos , Terapia Genética , Humanos , ARN Interferente Pequeño/genética , Globinas beta/genética
4.
Psychooncology ; 27(1): 265-271, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28727224

RESUMEN

OBJECTIVE: Needs assessment is the essence of quality cancer survivorship care. The aim of this study was to explore the supportive care needs of breast cancer survivors (BCS) in the first 5 years post treatment. METHODS: A mixed-methods approach was employed. A quantitative study included a Supportive Care Needs Survey, which was completed by 250 BCS to identify the level of their needs for help. The quantitative data informed semistructured qualitative interviews undertaken with 60 BCS to explore in detail their posttreatment needs and experiences. RESULTS: 32.4% and 16.8% reported 1 to 5 and greater than or equal to 6 needs for help, respectively. The regression analyses revealed that women within 2 years posttreatment and with higher educational level had higher levels of Psychological and Health Care System/Information needs. The qualitative data revealed "continuity of care" and "lifestyle advice and self-management" as prominent survivorship concerns. It was shown that determination to continue normal life, social support, and feeling overwhelmed by information were all experienced as important influences on survivors' need for help. CONCLUSIONS: Posttreatment needs vary with BCS characteristics and to the domains concerned. The approach to posttreatment care needs to be personalized and viable.


Asunto(s)
Neoplasias de la Mama/psicología , Supervivientes de Cáncer/psicología , Emociones , Calidad de Vida/psicología , Apoyo Social , Adulto , Neoplasias de la Mama/rehabilitación , Femenino , Necesidades y Demandas de Servicios de Salud , Humanos , Estilo de Vida , Persona de Mediana Edad , Calidad de la Atención de Salud
5.
Br J Anaesth ; 119(5): 934-942, 2017 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-28981592

RESUMEN

Background: The optimal volume status for neurosurgery has yet to be determined. We compared two fluid protocols based on different stroke volume variation (SVV) cut-offs for goal-directed fluid therapy (GDFT) during supratentorial brain tumour resection. Methods: A randomized, single-blind, open-label trial was conducted. Eighty adult patients undergoing elective supratentorial brain tumour resection were randomly divided into a low SVV and a high SVV group. The SVV cut-offs were used to determine when to initiate colloid infusion. Clinical outcomes and perioperative changes in serum neuronal biomarkers, including S100ß, neurone-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), were compared. Results: Patients in the low SVV group received a higher volume of colloid [869 (SD 404) vs 569 (453) ml; P=0.0025], had a higher urine output [3.4 (2.4) vs 2.5 (1.7) ml kg-1 h-1; P=0.0416] and a higher average cardiac index [3.2 (0.7) vs 2.8 (0.6) litres min-1 m-2; P=0.0204]. Patients in the low SVV group also had a shorter intensive care unit stay [1.4 (0.7) vs 2.6 (3.3) days, P=0.0326], fewer postoperative neurological events (17.5 vs 40%, P=0.0469), attenuated changes in the NSE and GFAP levels, lower intraoperative serum lactate and a higher Barthel index at discharge (all P<0.05). Conclusions: During GDFT for supratentorial brain tumour resection, fluid boluses targeting a lower SVV are more beneficial than a restrictive protocol. Clinical trial registration: NCT02113358.


Asunto(s)
Fluidoterapia/métodos , Cuidados Intraoperatorios/métodos , Volumen Sistólico/fisiología , Neoplasias Supratentoriales/cirugía , Encéfalo/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Simple Ciego , Resultado del Tratamiento
6.
Eur Rev Med Pharmacol Sci ; 20(16): 3378-84, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27608896

RESUMEN

OBJECTIVE: Glioma is the most lethal form of cancer that originates mostly from the brain and less frequently from the spine. Glioma is characterized by abnormal regulation of glial cell differentiation. The severity of the glioma was found to be relaxed in isocitrate dehydrogenase 1 (IDH1) mutant. The present study focused on histological discrimination and regulation of cancer stem cell between IDH1 mutant and in non-IDH1 mutant glioma tissue. PATIENTS AND METHODS: Histology, immunohistochemistry and Western blotting techniques are used to analyze the glioma nature and variation in glioma stem cells that differ between IDH1 mutant and in non-IDH1 mutant glioma tissue. RESULTS: The aggressive form of non-IDH1 mutant glioma shows abnormal cellular histological variation with prominent larger nucleus along with abnormal clustering of cells. The longer survival form of IDH1 mutant glioma has a control over glioma stem cell proliferation. Immunohistochemistry with stem cell markers, CD133 and EGFRvIII are used to demonstrate that the IDH1 mutant glioma shows limited dependence on cancer stem cells and it shows marked apoptotic signals in TUNEL assay to regulate abnormal cells. The non-IDH1 mutant glioma failed to regulate misbehaving cells and it promotes cancer stem cell proliferation. CONCLUSIONS: Our finding supports that the IDH1 mutant glioma has a regulatory role in glioma stem cells and their survival.


Asunto(s)
Glioma/genética , Isocitrato Deshidrogenasa , Neoplasias Encefálicas , Proliferación Celular , Glioma/patología , Humanos , Proteínas Mutantes , Mutación , Células Madre Neoplásicas
7.
Oncogenesis ; 4: e180, 2015 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-26690546

RESUMEN

The antitumor drug etoposide (ETO) is widely used in treating several cancers, including adrenocortical tumor (ACT). However, when used at sublethal doses, tumor cells still survive and are more susceptible to the recurring tumor due to centrosome amplification. Here, we checked the effect of sublethal dose of ETO in ACT cells. Sublethal dose of ETO treatment did not induce cell death but arrested the ACT cells in G2/M phase. This resulted in centrosome amplification and aberrant mitotic spindle formation leading to genomic instability and cellular senescence. Under such conditions, Chk2, cyclin A/CDK2 and ERK1/2 were aberrantly activated. Pharmacological inactivation of Chk2, CDK2 or ERK1/2 or depletion of CDK2 or Chk2 inhibited the centrosome amplification in ETO-treated ACT cells. In addition, autophagy was activated by ETO and was required for ACT cell survival. Chloroquine, the autophagy inhibitor, reduced ACT cell growth and inhibited ETO-induced centrosome amplification. Chloroquine alleviated CDK2 and ERK, but not Chk2, activation and thus inhibited centrosome amplification in either ETO- or hydroxyurea-treated ACT cells. In addition, chloroquine also inhibited centrosome amplification in osteosarcoma U2OS cell lines when treated with ETO or hydroxyurea. In summary, we have demonstrated that chloroquine inhibited ACT cell growth and alleviated DNA damage-induced centrosome amplification by inhibiting CDK2 and ERK activity, thus preventing genomic instability and recurrence of ACT.

8.
Haemophilia ; 21(1): e59-69, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25545305

RESUMEN

Ultrasmall paramagnetic iron oxide (USPIO)-enhanced MRI is promising for evaluating inflammation. The aims of this study were to investigate the effect of USPIO on cartilage T1 and T2 mapping, and to evaluate a proposed rapid vs. conventional T2 map method for imaging cartilage in a blood-induced arthritis model. Knees of nine arthritic (induction by intra-articular autologous blood injection) and six control rabbits were imaged over time (baseline, weeks 1, 5, 10) by 1.5 T MRI. All rabbits had USPIO (35-75 µmol Fe/kg)-enhanced MRI at each time point. T1 and T2 (conventional and rapid) maps and signal-to-noise ratios (SNR) were obtained pre- and post-USPIO administration. Cartilage biochemistry and histology were compared with MRI. Excellent correlations were noted between T1 map values and histologic scores at week 10 pre-USPIO (medial, r = 0.93, P = 0.0007; lateral, r = 0.87, P = 0.005) in the arthritic group, but not between T2 map and histology. Marginally and significant differences were observed between pre- and post-USPIO T2 values at weeks 5 (P = 0.06) and 10 (P = 0.02), but only with the administration of high USPIO doses in the arthritic group using the conventional method. No significant differences were noted between pre- and post-USPIO T1 values at any imaging time points. Cartilage T2 maps with short-TR and conventional protocols provided similar T2 values [(decreased trend)] (P > 0.05). Concomitant use of USPIO to T1 and T2 mapping of cartilage would not impair the identification of interval changes of T1 and T2 maps. Rapid T2 map provides similar results compared to conventional method, but its validation warrants further investigation.


Asunto(s)
Artritis/diagnóstico , Artritis/etiología , Sangre , Compuestos Férricos/química , Imagen por Resonancia Magnética/métodos , Nanopartículas , Animales , Artritis/patología , Modelos Animales de Enfermedad , Masculino , Proyectos Piloto , Conejos
9.
Eur J Clin Nutr ; 68(11): 1250-2, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24801367

RESUMEN

Although iron deficiency is common in women especially during dieting, weight management trials rarely examine the longitudinal impact of genetics on iron. This study examined the associations between the TMPRSS6 rs855791 polymorphism and iron indices at baseline and after a 12-month trial comparing two weight loss diets (higher-protein, higher-haem iron (HPHI) vs lower-protein, lower-haem iron (LPLI)). A total of 76 young overweight women (18-25y; BMI⩾27.5 kg/m(2)) were included at baseline, with 27 (HPHI: n=15; LPLI: n=12) completing the 12-month trial. At baseline, C allele homozygotes exhibited higher serum iron (P=0.047) and lower hepcidin (P=0.023) compared with T allele carriers. After 12 months, no genotypic differences were observed for ferritin and soluble transferrin receptor, although C homozygotes on HPHI showed higher serum iron and transferrin saturation (P<0.05). Results indicate that rs855791 can influence iron metabolism to some extent, but its impact on storage and functional iron status is small relative to dietary protein/iron manipulation.


Asunto(s)
Restricción Calórica , Hierro de la Dieta/administración & dosificación , Sobrepeso/dietoterapia , Sobrepeso/genética , Adolescente , Adulto , Alelos , Anemia Ferropénica/sangre , Anemia Ferropénica/dietoterapia , Índice de Masa Corporal , Estudios Transversales , Dieta Reductora , Proteínas en la Dieta/administración & dosificación , Ferritinas/sangre , Frecuencia de los Genes , Hepcidinas/sangre , Humanos , Hierro de la Dieta/sangre , Estudios Longitudinales , Sobrepeso/sangre , Polimorfismo Genético , Adulto Joven
10.
Diabetes Obes Metab ; 15(6): 572-5, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23279557

RESUMEN

UNLABELLED: Clinical research on weight management in young women is limited. This randomized controlled trial compared the efficacy of two iso-energetically restricted (5600 kJ) diets [higher protein (HP): 32% protein, 41% carbohydrate, 25% fat or higher carbohydrate (HC): 20, 58, 21%, respectively] in 71 (HP: n = 36; HC: n = 35) young healthy women (18-25 years; body mass index ≥ 27.5 kg/m2) for weight (kg; percent weight loss), body composition, metabolic and iron changes assessed at baseline, 6 and 12 months. DATA: mean (95% CI). In HP completers at 6 months, percent weight loss was higher [HP: 9.3 (5.6-13.1); HC: 5.1 (2.3-7.9)%; p = 0.06]; although, this did not reach statistical significance. Absolute weight [HP: 8.9 (5.3-12.5); HC: 4.6 (2.2-7.0) kg; p = 0.034] and fat loss [HP: 8.0 (4.4-11.5); HC: 3.4 (1.3-5.6) kg; p = 0.022] were significantly greater. No significant between-diet differences were observed at 12 months. Biochemistry remained within normal ranges with HP showing superior preservation of ferritin at 6 months [HP: 53 (40-66); HC: 46 (30-61) µg/l; p = 0.029]. Both diets supported clinically meaningful weight loss with HP tending to be more effective in the medium-term.


Asunto(s)
Dieta Reductora/métodos , Carbohidratos de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Sobrepeso/prevención & control , Adolescente , Adulto , Índice de Masa Corporal , Conducta Alimentaria , Femenino , Ferritinas/sangre , Humanos , Sobrepeso/sangre , Resultado del Tratamiento , Pérdida de Peso
11.
Infection ; 41(1): 247-50, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23001489

RESUMEN

We present a case of a patient with underlying protein S deficiency who suffered from infective endocarditis with a large anterior mitral leaflet (AML) mass of approximately 4.5 cm in length. Intraoperative transesophageal echocardiography (TEE) revealed the mass at the AML base and a rupture of the posterior mitral leaflet chordae tendinae. The vegetation's large size may have been caused by one or more of three factors: location, underlying disease, and the microorganism causing infection. Patients with protein S deficiency are prone to thromboembolic events during cardiac surgery. Infective endocarditis caused by Streptococcus agalactiae usually has a poor prognosis, and, thus, early surgery is recommended.


Asunto(s)
Endocarditis Bacteriana/complicaciones , Insuficiencia de la Válvula Mitral/complicaciones , Deficiencia de Proteína S/complicaciones , Infecciones Estreptocócicas/complicaciones , Anciano de 80 o más Años , Ecocardiografía Transesofágica , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/tratamiento farmacológico , Femenino , Humanos , Insuficiencia de la Válvula Mitral/diagnóstico , Insuficiencia de la Válvula Mitral/cirugía , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/tratamiento farmacológico , Resultado del Tratamiento
12.
Obes Rev ; 13(2): 150-61, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21981048

RESUMEN

A growing number of studies suggest a potential link between obesity and altered iron metabolism. The purpose of this systematic review was to examine existing literature on iron status in obese populations. A comprehensive literature search was conducted. Included studies recruited participants ≥ 18 years with a body mass index ≥ 30 kg m(-2) and provided descriptive statistics for haemoglobin or ferritin at a minimum. There were 25 studies meeting all eligibility criteria, of these 10 examined iron status in free-living obese individuals and 15 reported baseline iron biomarkers from bariatric surgery candidates. Non-obese comparison groups were used by 10 (40%) articles. In these, seven obese groups reported higher mean haemoglobin concentration; six reported significantly higher ferritin concentration; and four significantly lower transferrin saturation. Due to insufficient data, it was not possible to make conclusions regarding mean differences for soluble transferrin receptor (sTfR), hepcidin or C-reactive protein. Existing evidence suggests a tendency for higher haemoglobin and ferritin concentration and lower transferrin saturation in obesity. Alternation of iron biomarkers in obese populations may be a result of obesity-related inflammation and/or related comorbidities. Further research incorporating measurement of inflammatory cytokines, sTfR and hepcidin is required to confirm the impact of obesity on iron status.


Asunto(s)
Peso Corporal/fisiología , Deficiencias de Hierro , Hierro/metabolismo , Obesidad/sangre , Obesidad/fisiopatología , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Ferritinas/sangre , Hemoglobinas/metabolismo , Humanos , Hierro/sangre , Receptores de Transferrina/metabolismo , Transferrina/metabolismo
15.
Opt Lett ; 34(15): 2348-50, 2009 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-19649093

RESUMEN

We demonstrate what we believe to be the first use of AlGaInAs quantum wells (QWs) as a saturable absorber for a diode-pumped passively mode locked Nd:YVO(4) laser at 1342 nm. The QWs are grown on a Fe-doped InP substrate that is transparent at lasing wavelength. At an incident pump power of 13.5 W an average output power of 1.05 W with a continuous mode-locked pulse duration of 26.4 ps at a repetition rate of 152 MHz was generated.

17.
Inflammopharmacology ; 16(5): 201-7, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18815744

RESUMEN

Chinese medicated diet is an everyday practice in China. In this study, 16 commonly used soup making tonic Chinese medicinal herbs were selected for antioxidative capacities by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and ferric reducing antioxidant power (FRAP), and the total phenolic contents of these herbal extracts were measured by the Folin-Ciocalteu method. It confirmed that drinking tonic soups could supplement total antioxidants intake. Amongst the tested herbal extracts, extracts of Canarium album Raeusch., Flos caryophylli and Fructus amomi were found to have the highest antioxidative activities in both DPPH and FRAP assays. Their antioxidative activities were comparable to ascorbic acid and butylated hydroxytoluene. Thus, these herbs are safe and inexpensive sources of natural antioxidants. A significant relationship between the antioxidative effects and total phenolic contents were found, indicating phenolic compounds are the major contributor of antioxidative capacities of these herbs. In addition, a strong correlation between DPPH assay and FRAP assay implied that antioxidants in these herbs were capable of scavenging free radicals and reducing oxidants.


Asunto(s)
Antioxidantes/farmacología , Flavonoides/farmacología , Fenoles/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , China , Flavonoides/análisis , Depuradores de Radicales Libres/farmacología , Fenoles/análisis , Polifenoles
18.
Neuropharmacology ; 51(7-8): 1109-19, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16984802

RESUMEN

Our current understanding of the nature of cell death that is associated with fatal organophosphate poisoning and the underlying cellular mechanisms is surprisingly limited. Taking advantage of the absence in an in vitro system of acetylcholinesterase, the pharmacological target of organophosphate compounds, the present study evaluated the hypothesis that the repertoire of cholinergic receptor-independent cellular events that underlie fatal organophosphate poisoning entails induction of mitochondrial dysfunction, followed by bioenergetic failure that leads to necrotic cell death because of ATP depletion. Pheochromocytoma PC12 cells incubated with the organophosphate pesticide mevinphos (0.4 or 4mumol) for 1 or 3h underwent a dose-related and time-dependent loss of cell viability that was not reversed by muscarinic (atropine) or nicotinic (mecamylamine) blockade. This was accompanied by depressed NADH cytochrome c reductase, succinate cytochrome c reductase or cytochrome c oxidase activity in the mitochondrial respiratory chain, reduced mitochondrial transmembrane potential, decreased ATP concentration, elevated ADP/ATP ratio, increased lactate dehydrogenase release and necrotic cell death. We conclude that Mev induces cholinergic receptor-independent necrotic cell death by depressing the activity of Complexes I to IV in the mitochondrial respiratory chain, eliciting reduction in mitochondrial transmembrane potential, depleting intracellular ATP contents and damaging cell membrane integrity.


Asunto(s)
Adenosina Trifosfato/metabolismo , Transporte de Electrón/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Mevinfos/toxicidad , Mitocondrias/efectos de los fármacos , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Células PC12/efectos de los fármacos , Animales , Atropina/farmacología , Sustancias para la Guerra Química/farmacología , Sustancias para la Guerra Química/toxicidad , Colesterol/análogos & derivados , Colesterol/farmacología , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/toxicidad , Complejo IV de Transporte de Electrones/antagonistas & inhibidores , Insecticidas/farmacología , Insecticidas/toxicidad , L-Lactato Deshidrogenasa/análisis , Mecamilamina/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/fisiología , Mevinfos/antagonistas & inhibidores , Mevinfos/farmacología , Mitocondrias/enzimología , Mitocondrias/fisiología , Antagonistas Muscarínicos/farmacología , NADH Deshidrogenasa/antagonistas & inhibidores , Necrosis , Antagonistas Nicotínicos/farmacología , Fosforilación Oxidativa/efectos de los fármacos , Células PC12/fisiología , Polietilenglicoles/farmacología , Ratas , Receptores Colinérgicos/fisiología , Ubiquinona/farmacología
19.
Ecotoxicol Environ Saf ; 64(2): 226-33, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16406581

RESUMEN

Growth and physiological responses of rice to lanthanum were studied to elucidate the function of lanthanum in plants and its critical concentration relative to environmental safety. Shoot La content increased with the increasing added La concentrations. When shoot La content exceeded a toxic value, plant growth and chlorophyll a/b decreased and peroxidase (POD) activity, cell membrane permeability, and content of proline in the leaf increased. Leaf chlorophyll a/b and POD activity might provide useful criteria for early diagnoses of phytotoxicity of soil contaminated by La. In the present study, the critical concentration of La for rice relative to environmental safety was suggested to be 42.03 mg kg(-1) in red soil and 83.33 mg kg(-1) in paddy soil.


Asunto(s)
Lantano/toxicidad , Oryza , Semillas , Contaminantes del Suelo/toxicidad , Permeabilidad de la Membrana Celular/efectos de los fármacos , Clorofila/metabolismo , Clorofila A , Relación Dosis-Respuesta a Droga , Lantano/análisis , Oryza/efectos de los fármacos , Oryza/crecimiento & desarrollo , Oryza/fisiología , Peroxidasa/metabolismo , Hojas de la Planta/metabolismo , Semillas/efectos de los fármacos , Semillas/crecimiento & desarrollo , Semillas/fisiología , Suelo/análisis , Contaminantes del Suelo/análisis
20.
Br J Cancer ; 92(10): 1906-14, 2005 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-15870710

RESUMEN

Recepteur d'Origine Nantais (RON) is a distinct receptor tyrosine kinase in the c-met proto-oncogene family. We examined the mutational and expression patterns of RON in eight human uroepithelial cell lines. Biological effects of RON overexpression on cancer cells were investigated in vitro, and the prognostic significance of RON and/or c-met protein (MET) expression was analysed in a bladder cancer cohort (n=183). There was no evidence of mutation in the kinase domain of RON. Overexpression of RON using an inducible Tet-off system induced increased cell proliferation, motility, and antiapoptosis. Immunohistochemical analysis showed that RON was overexpressed in 60 cases (32.8%) of primary tumours, with 14 (23.3%) showing a high level of expression. Recepteur d'Origine Nantais expression was positively associated with histological grading, larger size, nonpapillary contour, and tumour stage (all P<0.01). In addition, MET was overexpressed in 82 cases (44.8%). Co-expressed RON and MET was significantly associated with decreased overall survival (P=0.005) or metastasis-free survival (P=0.01) in 35 cases (19.1%). Recepteur d'Origine Nantais-associated signalling may play an important role in the progression of human bladder cancer. Evaluation of RON and MET expression status may identify a subset of bladder-cancer patients who require more intensive treatment.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Transicionales/patología , Perfilación de la Expresión Génica , Proteínas Proto-Oncogénicas c-met/biosíntesis , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Tirosina Quinasas Receptoras/biosíntesis , Proteínas Tirosina Quinasas Receptoras/genética , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/genética , Estudios de Cohortes , Factor de Crecimiento de Hepatocito , Humanos , Inmunohistoquímica , Macrófagos , Reacción en Cadena de la Polimerasa , Pronóstico , Proto-Oncogenes Mas , Análisis de Supervivencia , Neoplasias de la Vejiga Urinaria/genética
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