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1.
Clin Radiol ; 79(4): e546-e553, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38238148

RESUMEN

AIM: To compare images using reduced CM, low-kVp scanning and DLR reconstruction with conventional images (no CM reduction, normal tube voltage, reconstructed with HBIR. To compare images using reduced contrast media (CM), low kilovoltage peak (kVp) scanning and deep-learning reconstruction (DLR) with conventional image quality (no CM reduction, normal tube voltage, reconstructed with hybrid-type iterative reconstruction method [HBIR protocol]). MATERIALS AND METHODS: A retrospective analysis was performed on 70 patients with liver disease and three-phase dynamic imaging using computed tomography (CT) from April 2020 to March 2022 at Oita University Hospital. Of these cases, 39 were reconstructed using the DLR protocol at a tube voltage of 80 kVp and CM of 300 mg iodine/kg while 31 were imaged at a tube voltage of 120 kVp with CM of 600 mg iodine/kg and were reconstructed by the usual HBIR protocol. Images from the DLR and HBIR protocols were analysed and compared based on the contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), figure-of-merit (FOM), and visual assessment. The CT dose index (CTDI)vol and size-specific dose estimates (SSDE) were compared with respect to radiation dose. RESULTS: The DLR protocol was superior, with significant differences in CNR, SNR, and FOM except hepatic parenchyma in the arterial phase. For visual assessment, the DLR protocol had better values for vascular visualisation for the portal vein, image noise, and contrast enhancement of the hepatic parenchyma. Regarding comparison of the radiation dose, the DLR protocol was superior for all values of CTDIvol and SSDE, with significant differences (p<0.01; max. 52%). CONCLUSION: Protocols using DLR with reduced CM and low kVp have better image quality and lower radiation dose compared to protocols using conventional HBIR.


Asunto(s)
Aprendizaje Profundo , Yodo , Humanos , Medios de Contraste , Estudios Retrospectivos , Dosis de Radiación , Tomografía Computarizada por Rayos X/métodos , Hígado/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Algoritmos
2.
Phys Rev Lett ; 126(24): 242301, 2021 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-34213947

RESUMEN

Using combined data from the Relativistic Heavy Ion and Large Hadron Colliders, we constrain the shear and bulk viscosities of quark-gluon plasma (QGP) at temperatures of ∼150-350 MeV. We use Bayesian inference to translate experimental and theoretical uncertainties into probabilistic constraints for the viscosities. With Bayesian model averaging we propagate an estimate of the model uncertainty generated by the transition from hydrodynamics to hadron transport in the plasma's final evolution stage, providing the most reliable phenomenological constraints to date on the QGP viscosities.

3.
Phys Chem Chem Phys ; 17(22): 14489-94, 2015 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-25866851

RESUMEN

Dye-sensitised solar cells (DSSCs) have sparked considerable interest over two decades. Recently, a method of polymer-wire sensitisation was demonstrated; the polymer is suggested to form a hole transport pathway (wire) following initial charge separation. We predict the optical properties of this polymer in various interfacial configurations, including the effects of chain length and attachment to {100} or {101} TiO2 facets. Contrary to most DSSCs, the {100} facet model best describes the experimental spectrum, predicting a relative thickness of 5.7 ± 0.2 µm, although {101} attachment, if implemented, may improve collection efficiency. Long chains are optimal, and stable attachment sites show minimal differences to absorbance in the major solar emission (visible) band. Combinations of {100}, {101}, and pseudo-bulk TiO2 models in three-parameter fits to experiment confirm the relative importance of the {100} facet.


Asunto(s)
Colorantes/química , Colorantes/efectos de la radiación , Suministros de Energía Eléctrica , Energía Solar , Titanio/química , Titanio/efectos de la radiación , Absorción de Radiación , Simulación por Computador , Transferencia de Energía , Diseño de Equipo , Análisis de Falla de Equipo , Luz , Ensayo de Materiales , Modelos Químicos , Teoría Cuántica , Propiedades de Superficie/efectos de la radiación
4.
Nanotechnology ; 20(21): 215302, 2009 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-19423928

RESUMEN

Photoetching of CdTe nanocrystals was applied to thiol-capped CdTe quantum dots (QDs) to control their fluorescence wavelength. CdTe QDs with a high quantum yield (49%) were synthesized in aqueous solution, and they were successfully photoetched in strong alkaline (pH = 13.5) conditions. When monochromatic light was used, size-selective photoetching could be conducted; the photoetching proceeded until the band gap energy of the CdTe QDs increased to the energy corresponding to the wavelength of the irradiating light. As a result, a good linear relationship was obtained between the wavelength of the irradiating light and that of the fluorescence peak. The resulting CdTe QDs exhibited a fluorescence peak with an FWHM value as small as 23.5 nm, indicating preparation of highly monodispersed nanocrystals. The high quantum yield (ca. 45%) was maintained after the photoetching. Very fine tuning of the fluorescence wavelength with 2 nm resolution was achieved by changing the wavelength of the irradiating light by 2 nm. Theoretical calculation of the quantum size effects (effective mass approximation) predicts that a difference in the band gap fluorescence wavelength of 2 nm corresponds to a change in particle diameter of ca. 0.02 nm.


Asunto(s)
Compuestos de Cadmio/química , Cristalización/métodos , Nanoestructuras/química , Nanotecnología/métodos , Fotoquímica/métodos , Puntos Cuánticos , Espectrometría de Fluorescencia/métodos , Telurio/química , Sustancias Macromoleculares/química , Ensayo de Materiales , Conformación Molecular , Nanoestructuras/ultraestructura , Tamaño de la Partícula , Propiedades de Superficie
5.
AJNR Am J Neuroradiol ; 40(2): 224-230, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30630834

RESUMEN

BACKGROUND AND PURPOSE: Synthetic FLAIR images are of lower quality than conventional FLAIR images. Here, we aimed to improve the synthetic FLAIR image quality using deep learning with pixel-by-pixel translation through conditional generative adversarial network training. MATERIALS AND METHODS: Forty patients with MS were prospectively included and scanned (3T) to acquire synthetic MR imaging and conventional FLAIR images. Synthetic FLAIR images were created with the SyMRI software. Acquired data were divided into 30 training and 10 test datasets. A conditional generative adversarial network was trained to generate improved FLAIR images from raw synthetic MR imaging data using conventional FLAIR images as targets. The peak signal-to-noise ratio, normalized root mean square error, and the Dice index of MS lesion maps were calculated for synthetic and deep learning FLAIR images against conventional FLAIR images, respectively. Lesion conspicuity and the existence of artifacts were visually assessed. RESULTS: The peak signal-to-noise ratio and normalized root mean square error were significantly higher and lower, respectively, in generated-versus-synthetic FLAIR images in aggregate intracranial tissues and all tissue segments (all P < .001). The Dice index of lesion maps and visual lesion conspicuity were comparable between generated and synthetic FLAIR images (P = 1 and .59, respectively). Generated FLAIR images showed fewer granular artifacts (P = .003) and swelling artifacts (in all cases) than synthetic FLAIR images. CONCLUSIONS: Using deep learning, we improved the synthetic FLAIR image quality by generating FLAIR images that have contrast closer to that of conventional FLAIR images and fewer granular and swelling artifacts, while preserving the lesion contrast.


Asunto(s)
Encéfalo/diagnóstico por imagen , Aprendizaje Profundo , Interpretación de Imagen Asistida por Computador/métodos , Neuroimagen/métodos , Adulto , Artefactos , Encéfalo/patología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Programas Informáticos
6.
Neuroscience ; 324: 307-20, 2016 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-26987956

RESUMEN

The supratrigeminal nucleus (Vsup), originally proposed as a premotoneuron pool in the trigeminal reflex arc, is a key structure of jaw movement control. Surprisingly, however, the location of the rat Vsup has not precisely been defined. In light of our previous cat studies, we made two hypotheses regarding the rat Vsup: (1) the Vsup is cytoarchitectonically distinguishable from its surrounding structures; (2) the Vsup receives central axon terminals of the trigeminal mesencephalic nucleus (Vmes) neurons which are primary afferents innervating muscle spindles of jaw-closing muscles and periodontal ligaments around the teeth. To test the first hypothesis, we examined the cytoarchitecture of the rat Vsup. The Vsup was identified as an area medially adjacent to the dorsomedial part of trigeminal principal sensory nucleus (Vp), and extended from the level just rostral to the caudal two-thirds of the trigeminal motor nucleus (Vmo) to the level approximately 150 µm caudal to the Vmo. Our rat Vsup was much smaller and its location was considerably different in comparison to the Vsup reported previously. To evaluate the second hypothesis, we tested the distribution patterns of Vmes primary afferent terminals in the cytoarchitectonically identified Vsup. After transganglionic tracer applications to the masseter, deep temporal, and medial pterygoid nerves, a large number of axon terminals were observed in all parts of Vsup (especially in its medial part). After applications to the inferior alveolar, infraorbital, and lingual nerves, a small number of axon terminals were labeled in the caudolateral Vsup. The Vsup could also be identified electrophysiologically. After electrical stimulation of the masseter nerve, evoked potentials with slow negative component were isolated only in the Vsup. The present findings suggest that the rat Vsup can be cytoarchitectonically and electrophysiologically identified, receives somatotopic termination of the trigeminal primary afferents, and principally receives strong termination of the spindle Vmes primary afferents.


Asunto(s)
Tronco Encefálico/anatomía & histología , Tronco Encefálico/fisiología , Animales , Axones/fisiología , Estimulación Eléctrica , Potenciales Evocados , Maxilares/anatomía & histología , Maxilares/inervación , Maxilares/fisiología , Masculino , Músculo Esquelético/anatomía & histología , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Técnicas de Trazados de Vías Neuroanatómicas , Neuronas Aferentes/citología , Neuronas Aferentes/fisiología , Fotomicrografía , Ratas Wistar
7.
Biochim Biophys Acta ; 754(1): 21-7, 1983 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-6626564

RESUMEN

The relationship between hepatic fatty acid-binding protein and peroxisomal beta-oxidation was studied. Rats were fed a diet containing p-chlorophenoxyisobutyric acid (clofibric acid), 2,2'-(decamethylenedithio)-diethanol (tiadenol), di-(2-ethylhexyl)-phthalate (DEHP), di-(2-ethylhexyl)-adipate (DEHA) and acetylsalicylic acid. On the administration of these peroxisome proliferators, both [1-14C]oleic acid-binding capacity and content of fatty acid-binding protein were increased, in association with an increase in peroxisomal beta-oxidation activity. The order of the increase in binding capacity and content of fatty acid-binding protein was tiadenol greater than DEHP greater than or equal to clofibric acid greater than DEHA = acetylsalicylic acid. The order of the increase in peroxisomal beta-oxidation activity in liver was tiadenol greater than clofibric acid greater than or equal to DEHP greater than DEHA = acetylsalicylic acid. Linear regression analysis between the binding capacity or content of fatty acid-binding protein and peroxisomal beta-oxidation activity was highly significant.


Asunto(s)
Proteínas Portadoras/metabolismo , Hígado/metabolismo , Microcuerpos/efectos de los fármacos , Proteínas de Neoplasias , Proteínas del Tejido Nervioso , Adipatos/farmacología , Animales , Aspirina/farmacología , Sitios de Unión/efectos de los fármacos , Proteínas Portadoras/aislamiento & purificación , Cromatografía de Afinidad , Ácido Clofíbrico/farmacología , Citosol/metabolismo , Dietilhexil Ftalato , Proteína de Unión a los Ácidos Grasos 7 , Proteínas de Unión a Ácidos Grasos , Alcoholes Grasos/farmacología , Masculino , Oxidación-Reducción , Ratas , Ratas Endogámicas
8.
Biochim Biophys Acta ; 1291(1): 89-95, 1996 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-8781530

RESUMEN

1,5-Anhydro-D-glucitol (AG) is a major polyol, 99.9% of which is reabsorbed by the kidney. However, such reabsorption is inhibited by competition with glucose excreted in excess, i.e., glucosuria. Under such conditions, AG is excreted into the urine. We administered various types of sugars to rats by continuous intravenous infusion for two hours to evaluate the competition between AG and these sugars for renal reabsorption in vivo. The reabsorption of AG was significantly inhibited by competition with fructose and mannose. The excretion of AG in the 120 min after a load of 3.64 mmol of fructose was 1.99 +/- 0.33 mumol, that after 3.64 mmol of mannose loading was 2.34 +/- 0.43 mumol. These levels were comparable to the AG excretion observed after the administration of the same amount of glucose (3.87 +/- 0.61 mumol). No competition was observed with sucrose, xylose, myoinositol or galactose. The reabsorption of fructose and mannose was significantly inhibited by the presence of AG (P < 0.001) after a mixed load. Results suggest that AG is reabsorbed in the renal tubule by an AG/fructose/mannose-common transport system that is distinct from the major glucose reabsorption system. These findings may help to clarify the specific transport systems for various sugars in the renal tubule, as well as their physiological importance.


Asunto(s)
Desoxiglucosa/metabolismo , Fructosa/metabolismo , Túbulos Renales/metabolismo , Manosa/metabolismo , Proteínas de Transporte de Monosacáridos/fisiología , Absorción , Animales , Glucemia/análisis , Carbohidratos/sangre , Carbohidratos/orina , Desoxiglucosa/sangre , Desoxiglucosa/farmacología , Desoxiglucosa/orina , Fructosa/sangre , Fructosa/farmacología , Fructosa/orina , Glucosuria/metabolismo , Masculino , Manosa/sangre , Manosa/farmacología , Manosa/orina , Ratas , Ratas Wistar
9.
J Clin Endocrinol Metab ; 56(6): 1327-31, 1983 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-6404925

RESUMEN

We measured FSH and LH concentrations by RIA in 130 cord sera and 213 peripheral sera obtained as serially as possible from 67 infants who were 5-75 days old and were born between the 28th and 42nd gestational weeks. Cord serum FSH and LH (+hCG) levels were 3.9-13.6 mIU/ml and 43.3-88.6 mIU/ml, respectively; they decreased with advancing gestational age. Postnatal FSH levels in male infants maintained low levels (3.7-8.7 mIU/ml). However, those in female infants increased with peak levels (51.8-270.3 mIU/ml) between 11 and 30 days after delivery, and then decreased; the surge was more marked and prolonged in preterm infants than in term infants. Postnatal LH levels in both sexes decreased rapidly after birth, which may be due to a decrease of placental hCG, and thereafter displayed patterns similar to FSH levels. We found a significant sex difference of serum gonadotropin levels in newborn infants and differences between term and preterm infants. Our results suggest that the sex difference of pituitary gonadal function exists and that the function matures during the fetal and neonatal life.


Asunto(s)
Gonadotropina Coriónica/sangre , Hormona Folículo Estimulante/sangre , Recien Nacido Prematuro , Hormona Luteinizante/sangre , Femenino , Sangre Fetal , Edad Gestacional , Humanos , Recién Nacido , Masculino
10.
FEBS Lett ; 207(1): 162-6, 1986 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-3095142

RESUMEN

Suppressor [32P]phosphoseryl-tRNA, prepared using bovine seryl-tRNA synthetase and ATP:seryl-tRNA phosphotransferase, was mixed with rabbit reticulocyte lysates containing endogenous hemoglobin mRNA having the termination codon UGA (opal). The chromatographic pattern of the lysate on Sephacryl S-200 showed that the radioactivity of [32P]phosphate in the hot trichloroacetic acid-precipitate (phosphoprotein) was eluted at the position between mature hemoglobin and globin subunits. The phosphoprotein, obtained by chromatography on S-200, moved to the position corresponding to that of globin readthrough protein on SDS-PAGE. The analyses of the hydrolyzate of the phosphoprotein showed the presence of phosphoserine in the protein. These results suggest that animal opal suppressor tRNA functions in vitro to transfer phosphoserine to the position of the termination codon UGA (opal) on mRNA.


Asunto(s)
Hemoglobinas/biosíntesis , Fosfoserina/metabolismo , Aminoacil-ARN de Transferencia/fisiología , Serina/análogos & derivados , Supresión Genética , Animales , Bovinos , Codón , Conejos
11.
J Hypertens ; 5(6): 749-53, 1987 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-3429875

RESUMEN

To investigate the clinical usefulness of radio-immunoassay of neuropeptide Y (NPY), we measured plasma immunoreactive neuropeptide Y (IR-NPY) concentrations in normal subjects (n = 21), essential hypertensive patients (n = 33), patients with phaeochromocytoma (n = 7), patients with chronic renal disease with serum creatinine levels of less than 1.9 mg/dl (n = 5) and patients with chronic renal failure whose serum creatinine levels were greater than or equal to 1.9 mg/dl (n = 18, eight without haemodialysis and 10 undergoing maintenance haemodialysis), by radio-immunoassay. Plasma IR-NPY concentrations in patients with phaeochromocytoma (577 +/- 256 pg/ml, mean +/- s.d.) were significantly higher (P less than 0.001) than those in normal subjects (151 +/- 28 pg/ml), essential hypertensive patients (177 +/- 49 pg/ml) and patients with chronic renal disease with serum creatinine levels less than 1.9 mg/dl (198 +/- 71 pg/ml). Plasma IR-NPY concentrations in patients with chronic renal failure (without haemodialysis: 330 +/- 63 pg/ml; undergoing maintenance haemodialysis: 374 +/- 80 pg/ml) were also high. These results suggest that NPY is useful as one of the tumour markers of phaeochromocytomas. However, this study revealed that patients with chronic renal failure, without phaeochromocytoma also have increased plasma IR-NPY concentrations.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/sangre , Hipertensión/sangre , Fallo Renal Crónico/sangre , Neuropéptido Y/sangre , Feocromocitoma/sangre , Adulto , Cromatografía en Gel , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioinmunoensayo , Diálisis Renal
12.
J Med Chem ; 44(9): 1422-8, 2001 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-11311065

RESUMEN

2-Fluoropodophyllotoxin (11) and several 4beta-anilino-2-fluoro-4'-O-demethyl analogues were synthesized and evaluated in both antineoplastic and antiviral assays. These compounds were moderately active against some cancer cell lines, but they were less active than the corresponding nonfluorinated analogues. Compound 11 exhibited the best activity against KB carcinoma with a GI(50) of approximately 30 nM. Most compounds exhibited moderate activity against HCMV with ID(50) and ID(90) values in the range of 1 microM and 4 microM, respectively. Both 9 and 11 showed an unusual 10-fold selectivity for HSV-2 compared to HSV-1.


Asunto(s)
Antineoplásicos/síntesis química , Antivirales/síntesis química , Podofilotoxina/análogos & derivados , Podofilotoxina/síntesis química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antivirales/química , Antivirales/farmacología , Chlorocebus aethiops , ADN/química , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 2/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Hibridación de Ácido Nucleico , Podofilotoxina/química , Podofilotoxina/farmacología , Relación Estructura-Actividad , Células Tumorales Cultivadas , Células Vero
13.
J Med Chem ; 42(20): 4081-7, 1999 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-10514278

RESUMEN

As part of our continuing search for potential anticancer drug candidates in the 2-aryl-1,8-naphthyridin-4-one series, we have synthesized a series of substituted 2-thienyl-1, 8-naphthyridin-4-ones. Most compounds showed significant cytotoxic effects (log GI(50) < -4.0; log molar drug concentration required to cause 50% growth inhibition) against a variety of human tumor cell lines in the National Cancer Institute's in vitro screen, including cells derived from solid tumors such as non-small-cell lung, colon, central nervous system, melanoma, ovarian, prostate, and breast cancers. The most active compounds (31-33,40) demonstrated strong cytotoxic effects with ED(50) values in the micromolar or submicromolar range in most of the tumor cell lines. The most cytotoxic compounds inhibited tubulin polymerization at concentrations substoichiometric to the tubulin concentration. The most potent inhibitors of polymerization (40,42,43) had effects comparable to those of the potent antimitotic natural products podophyllotoxin and combretastatin A-4 and to that of NSC 664171, a particularly potent, structurally related analogue. Only compound 40 was a potent inhibitor of the binding of radiolabeled colchicine to tubulin, and it was both the most cytotoxic agent and the most effective inhibitor of polymerization among the newly synthesized compounds.


Asunto(s)
Antineoplásicos/síntesis química , Naftiridinas/síntesis química , Tiofenos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Biopolímeros , Colchicina/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración 50 Inhibidora , Modelos Moleculares , Naftiridinas/química , Naftiridinas/farmacología , Relación Estructura-Actividad , Tiofenos/química , Tiofenos/farmacología , Tubulina (Proteína)/química , Células Tumorales Cultivadas
14.
J Med Chem ; 41(7): 1155-62, 1998 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-9544215

RESUMEN

A novel series of 6,7,2',3',4'-substituted-1,2,3,4-tetrahydro-2-phenyl- 4-quinolones were synthesized and evaluated for interactions with tubulin and for cytotoxic activity against a panel of human tumor cell lines, including ileocecal carcinoma (HCT-8), breast cancer (MCF-7), lung carcinoma (A-549), epidermoid carcinoma of the nasopharynx (KB), renal cancer (CAKI-1), and melanoma cancer (SKMEL-2). Most compounds (18, 20, 22-27) showed potent cytotoxic and antitubulin effects. The most active compounds (23, 26, 27) demonstrated strong cytotoxic effects with ED50 values in the nanomolar or subnanomolar range in almost all tumor cell lines. Three active racemates (20, 22, 25) were separated into the enantiomers, and generally, the optically pure (-)-isomers (20a, 22a, 25a) exhibited greater biological activity than the racemates or (+)-isomers. Cytotoxicity and antitubulin activity were closely correlated, with the most active compounds (23, 26, 27) having effects comparable to those of colchicine, podophyllotoxin, and combretastatin A-4.


Asunto(s)
Antibióticos Antineoplásicos/síntesis química , Quinolonas/síntesis química , Tubulina (Proteína)/metabolismo , Antibióticos Antineoplásicos/farmacología , Humanos , Quinolonas/farmacología , Células Tumorales Cultivadas/efectos de los fármacos
15.
J Med Chem ; 41(11): 1956-61, 1998 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-9599244

RESUMEN

Several 1,2,3-tridemethyldeacetylthiocolchicine derivatives have been synthesized and evaluated for cytotoxic activity against various human tumor cell lines and for their inhibitory effects on DNA topoisomerases in vitro. Exhaustive demethylation of thiocolchicine analogues completely changes their biological profiles. Instead of displaying antitubulin activity, most target compounds inhibited topoisomerase II activity. Only compounds with a larger side chain, such as 15a, 23a, and 24a, did not interfere with topoisomerase II enzymatic functions. The cytotoxicity of target compounds was reduced by 3 orders of magnitude compared to that of colchicine in most cell lines. The hydrophilicity of phenolic compounds might prevent drug passage through the cell plasma membrane and, thus, be responsible for the relatively weak cytotoxicity. To test this hypothesis, 27-30 were prepared from 16a by protecting all hydroxy groups with esters with an aim to facilitate drug transportation. In vitro cytotoxicity assays indicated that 27 was more potent than its parent compound in all tested tumor cell lines and showed tissue selective cytotoxicity with a significant inhibitory effect against KB cells (IC50 = 2.7 microg/mL). Therefore, we propose that 27 acts as a prodrug, liberating 16a to exert its antitopoisomerase activity and, finally, to cause cell death.


Asunto(s)
Antineoplásicos , Colchicina/análogos & derivados , Inhibidores Enzimáticos , Inhibidores de Topoisomerasa II , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , División Celular/efectos de los fármacos , Colchicina/síntesis química , Colchicina/metabolismo , Colchicina/farmacología , ADN/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Humanos , Células KB , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina , Células Tumorales Cultivadas
16.
J Med Chem ; 42(13): 2441-6, 1999 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-10395485

RESUMEN

As a continuation of our structure-activity relationship studies, several new 4-beta-substituted 4'-O-demethyl-4-desoxypodophyllotoxins bearing mono-, di-, or trisubstituted anilines have been synthesized and evaluated as inhibitors of DNA topoisomerase II and tumor cell growth in tissue culture. Selected compounds were further evaluated as cytotoxic agents using a clonogenic survival assay. The target compounds include 4'-O-demethyl-4beta-[(4' '-(benzimidazol-2' '-yl)anilino]-4-desoxypodophyllotoxin (21), 4'-O-demethyl-4beta-(-)-(4' '-camphanamido-anilino)-4-desoxypodophyllotoxin (25), 4-beta-disubstituted-anilino-4'-demethyl-4-desoxypodophyllotoxins (18-20, 26), 4-alpha-disubstituted-anilino-4'-demethyl-4-desoxypodophyllotoxin (27), 4-beta-trisubstituted-anilino-4'-demethyl-desoxypodophyllotoxin (22, 23), and 4'-O-demethyl-4beta-[4' '-(benzimidazol-2' '-yl)amino]-4-desoxypodophyllotoxin (24). Among the target series, 19, 21, and 24 displayed significant growth inhibitory action against a panel of tumor cell lines including human epidermoid carcinoma of the nasopharynx (KB) and its etoposide-resistant (KB7B) and vincristine-resistant (vin20c KB) subclones, lung carcinoma (A549), human ileocecal carcinoma (HCT-8), human kidney carcinoma (CAKI-1), breast adenocarcinoma (MCF-7), and human malignant melanoma (SK-MEL-2) cells. Compounds 19, 21, 24, and 25 were "cleavable-complex"-forming DNA topoisomerase II inhibitors with either improved or similar activity compared with the prototype drug etoposide (VP-16). Compound 21 was the most active analogue, being 10-fold more potent than etoposide in both cell killing and topoisomerase II inhibition in vitro assays. Using mouse models of antitumor activity, 21 was effective against (P388/0) leukemia but not against the growth of a (MCF7) mammary tumor.


Asunto(s)
Antineoplásicos/síntesis química , Bencimidazoles/síntesis química , Etopósido/análogos & derivados , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Bencimidazoles/química , Bencimidazoles/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Etopósido/síntesis química , Etopósido/química , Etopósido/farmacología , Femenino , Humanos , Concentración 50 Inhibidora , Leucemia P388/tratamiento farmacológico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Relación Estructura-Actividad , Inhibidores de Topoisomerasa II , Células Tumorales Cultivadas
17.
Cancer Lett ; 158(2): 151-4, 2000 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-10960764

RESUMEN

Seven taxane diterpenes were isolated from the EtOH extract of the aerial parts of Taxus chinensis, and evaluated for cytotoxicity against nine human cell lines, including a beta-tublin mutant resistant to paclitaxel. Compound 2, a non-alkaloid-type taxane diterpene, showed significant cytotoxicity in most cell lines, and notably, equipotent against both parental and beta-tublin mutant tumor cell lines.


Asunto(s)
Diterpenos/farmacología , Resistencia a Antineoplásicos , Paclitaxel/farmacología , Plantas Medicinales , Taxus/química , Supervivencia Celular/efectos de los fármacos , Diterpenos/química , Humanos , Células Tumorales Cultivadas/citología , Células Tumorales Cultivadas/efectos de los fármacos
18.
J Biochem ; 90(5): 1281-9, 1981 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-6175619

RESUMEN

About thirty percent of two alpha-amylases produced from a serous papillary cystadenocarcinoma of the ovarium (case 1) and a bronchioloalveolar adenocarcinoma of the lung (case 2) was glycoproteins containing 1 mol of asparagine-linked sugar chain, respectively. The structures of the sugar moieties were found by sequential enzymatic degradation and methylation analysis to be as follows: [(Gal beta 1 leads to 4)0 or 1GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(3)][GlcNAc beta 1 leads to 2Man alpha 1 leads to 3(6)]Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc and [(Gal beta 1 leads to 4)0 or 1GlcNAc beta 1 leads to 2Man alpha 1 leads to 6][NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3]Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc. Structures of asparagine-linked sugar chains were the same in the tumors of cases 1 and 2 and were incomplete in comparison with those of the parotid amylase.


Asunto(s)
Adenocarcinoma/enzimología , Amilasas/aislamiento & purificación , Carbohidratos/aislamiento & purificación , Cistadenocarcinoma/enzimología , Neoplasias Pulmonares/enzimología , Neoplasias Ováricas/enzimología , alfa-Amilasas/aislamiento & purificación , Fenómenos Químicos , Química , Femenino , Humanos
19.
J Biochem ; 93(1): 135-47, 1983 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-6132915

RESUMEN

The carbohydrate moieties of gamma-glutamyltranspeptidase (gamma-GTP) purified from bovine kidney were chemically released as oligosaccharides. The oligosaccharide mixture was fractionated into a neutral fraction and three groups of acidic fractions containing one, two, and three sialic acid residues. Both the neutral fractions and the neutral oligosaccharide mixture obtained from the pooled sample of all acidic fractions by sialidase treatment were separated into seven components by Bio-Gel P-4 column chromatography. Structural studies of these components by sequential exoglycosidase digestion in combination with methylation analysis indicated that the gamma-GTP contains at least twelve neutral sugar chains which are either the high mannose type, or the bi- and triantennary complex type, and thirteen acidic sugar chains of the bi-, tri-, and tetraantennary complex type. The characteristics feature of the sugar chains of the gamma-GTP is that most of the complex type sugar chains contain an N-acetylglucosamine residue at the C-4 position of the beta-mannosyl residue of their trimannosyl core, and their outer chain moieties are enriched in non-reducing terminal beta-N-acetylglucosamine residues.


Asunto(s)
Carbohidratos/aislamiento & purificación , Riñón/enzimología , gamma-Glutamiltransferasa/aislamiento & purificación , Animales , Bovinos , Fenómenos Químicos , Química , Glicósido Hidrolasas
20.
J Biochem ; 90(5): 1291-6, 1981 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-6802807

RESUMEN

The substrate specificity of human endo-beta-N-acetylglucosaminidase was studied by using the homogenate of cultured skin fibroblasts of fucosidosis patients as an enzyme source. The results indicate that biantennary complex type asparagine-linked sugar chains as well as high mannose type sugar chains are cleaved by the enzyme action. None of the sugar chains with a fucosyl residue on the proximal N-acetylglucosamine of their N,N'-diacetylchitobiose moieties was cleaved. These results proved enzymatically the mechanism of production of oligosaccharides detected in the urine of various exoglycosidase deficiencies.


Asunto(s)
Acetilglucosaminidasa/fisiología , Asparagina/metabolismo , Errores Innatos del Metabolismo de los Carbohidratos/enzimología , Fucosa/metabolismo , Hexosaminidasas/fisiología , Oligosacáridos/metabolismo , Piel/enzimología , Fibroblastos/enzimología , Humanos , Hidrólisis , Manosil-Glicoproteína Endo-beta-N-Acetilglucosaminidasa , Especificidad por Sustrato
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