Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
1.
Toxicol Appl Pharmacol ; 278(2): 100-6, 2014 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-24768707

RESUMEN

The caspase inhibitor benzyloxycarbony (Cbz)-l-Val-Ala-Asp (OMe)-fluoromethylketone (z-VAD-FMK) has recently been shown to inhibit T cell proliferation without blocking caspase-8 and caspase-3 activation in primary T cells. We showed in this study that z-VAD-FMK treatment leads to a decrease in intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) levels in activated T cells. The inhibition of anti-CD3-mediated T cell proliferation induced by z-VAD-FMK was abolished by the presence of low molecular weight thiols such as GSH, N-acetylcysteine (NAC) and l-cysteine, whereas d-cysteine which cannot be metabolised to GSH has no effect. These results suggest that the depletion of intracellular GSH is the underlying cause of z-VAD-FMK-mediated inhibition of T cell activation and proliferation. The presence of exogenous GSH also attenuated the inhibition of anti-CD3-induced CD25 and CD69 expression mediated by z-VAD-FMK. However, none of the low molecular weight thiols were able to restore the caspase-inhibitory properties of z-VAD-FMK in activated T cells where caspase-8 and caspase-3 remain activated and processed into their respective subunits in the presence of the caspase inhibitor. This suggests that the inhibition of T cell proliferation can be uncoupled from the caspase-inhibitory properties of z-VAD-FMK. Taken together, the immunosuppressive effects in primary T cells mediated by z-VAD-FMK are due to oxidative stress via the depletion of GSH.


Asunto(s)
Clorometilcetonas de Aminoácidos/farmacología , Inhibidores de Caspasas/farmacología , Proliferación Celular , Inhibidores de Crecimiento/farmacología , Activación de Linfocitos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Subgrupos de Linfocitos T/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta Inmunológica , Glutatión/metabolismo , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Activación de Linfocitos/inmunología , Activación de Linfocitos/fisiología , Estrés Oxidativo/inmunología , Especies Reactivas de Oxígeno/metabolismo , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología
3.
J Clin Neurosci ; 19(3): 477-8, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22249016

RESUMEN

Ollier disease is a rare disorder characterised by the development of multiple enchondromas in long bones. Here we present a 19-year-old man with Ollier disease who also developed three synchronous brain tumours. Craniotomy, biopsy and debulking was performed for one lesion followed by a period of observation, and 9 months later he underwent a second craniotomy and debulking for symptomatic progression. Histopathological examination revealed a diagnosis of multifocal diffuse glioma (World Health Organization grade II). This report highlights the increased incidence of primary brain tumours in patients with Ollier disease and identifies the importance of screening patients with Ollier disease for primary neoplasms.


Asunto(s)
Encondromatosis/patología , Glioma/patología , Neoplasias Supratentoriales/patología , Astrocitoma/patología , Astrocitoma/cirugía , Biopsia , Encéfalo/patología , Condroma/complicaciones , Condroma/cirugía , Encondromatosis/complicaciones , Glioma/complicaciones , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Masculino , Procedimientos Neuroquirúrgicos , Radiocirugia , Neoplasias Supratentoriales/complicaciones , Proteína p53 Supresora de Tumor/metabolismo , Adulto Joven
5.
Neurology ; 60(2): 326-8, 2003 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-12552054

RESUMEN

Posterior leukoencephalopathy syndromes have been reported with hypertension, and immunosuppressive and chemotherapy agents. Cerebral vasospasm on MR angiography (MRA) has been noted in cases due to eclampsia. The authors report a case of Balint syndrome with irreversible posterior leukoencephalopathy on MRI following intrathecal methotrexate and cytarabine. Hypertension was not present. Diffuse, reversible arterial irregularities consistent with vasospasm were present on MRA during the acute illness.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Encefalopatías/inducido químicamente , Encefalopatías/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Vasoespasmo Intracraneal/inducido químicamente , Enfermedad Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ceguera/etiología , Encefalopatías/fisiopatología , Arterias Cerebrales/patología , Arterias Cerebrales/fisiopatología , Infarto Cerebral/etiología , Citarabina/administración & dosificación , Citarabina/efectos adversos , Progresión de la Enfermedad , Femenino , Humanos , Inyecciones Espinales , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Trastornos de la Motilidad Ocular/etiología , Recuperación de la Función , Síndrome , Taquicardia/complicaciones , Taquicardia/diagnóstico , Vasoespasmo Intracraneal/diagnóstico , Vasoespasmo Intracraneal/fisiopatología
7.
Chemotherapy ; 47(1): 56-69, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11125234

RESUMEN

The motile behavior of tumor cells is regulated in part by growth factors, cytokines, and other endogenous factors. In some instances, stromal tissue surrounding the tumor cells produces these growth factors which interact with tumor cells and thus may play an important role in tumor proliferation and progression. We and others have shown that conditioned media from NIH 3T3 fibroblasts (3T3-CM) increases the invasiveness of breast cancer cells. The present study characterized the influence of 3T3-CM on breast cancer cell motility and examined the hypothesis that antiestrogens inhibit this 3T3-CM-induced effect. In this study we observed that 3T3-CM added to MCF-7 cells produced an immediate cell-scattering effect as determined by time-lapse videomicroscopy, scanning electron microscopy, and F-actin labeling. The results of this study indicate that keratinocyte growth factor in 3T3-CM is largely responsible for the 3T3-CM-induced scattering motility of MCF-7 cells. These results emphasize the importance of stromal-tumor cell (epithelial-mesenchymal) interactions in the motility of breast cancer cells. Further, our results demonstrate that antiestrogens (tamoxifen, ICI-182,780 and Analog II) inhibit 3T3-CM-induced motility of MCF-7 breast cancer cells. Antiestrogen treatment reduced membrane movements and the motile morphology of MCF-7 cells induced by 3T3-CM. These results suggest that antiestrogens inhibit breast cancer cell motility and that antiestrogen treatment may be used to reduce the metastatic spread of breast cancer.


Asunto(s)
Células 3T3/fisiología , Neoplasias de la Mama/patología , Movimiento Celular/efectos de los fármacos , Moduladores de los Receptores de Estrógeno/farmacología , Animales , Humanos , Ratones , Invasividad Neoplásica , Metástasis de la Neoplasia , Células Tumorales Cultivadas
10.
Cancer Invest ; 17(1): 10-8, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10999044

RESUMEN

Metastatic spread of breast cancer is responsible for most of the morbidity and mortality associated with this disease. Thus, it is important to identify agents with antimetastatic activity. Because invasiveness and tumor cell attachment are fundamental steps in the metastatic cascade, the major objective of the present study was to evaluate the antimetastatic potential of three antiestrogens, each with different chemical structure and mechanism of action, on breast cancer cell invasiveness and laminin attachment. The antiestrogens examined were tamoxifen, a mixed antagonist/agonist; Analog II, a cyclopropyl antiestrogen with pure antagonist activity; and ICI-182,780, a steroidal antiestrogen with pure antagonist activity. Our results indicate that MDA-MB-231 human breast cancer cells are much more invasive and have a higher affinity for laminin than do MCF-7 human breast cancer cells. All three antiestrogens, at a concentration of 10(-6) M, produced a reduction in MDA-MB-231 cell invasiveness, which was comparable in magnitude to their inhibition of MDA-MB-231 attachment to laminin. Evaluation of MDA-MB-231 cell morphology using scanning electron microscopy revealed the involvement of cellular pseudopodia and microvilli in the process of invasion. The results of this study suggest that antiestrogen-induced inhibition of breast cancer cell invasiveness could be due in part to a decrease in the attachment of tumor cells to laminin in the basement membrane.


Asunto(s)
Adenocarcinoma/patología , Antineoplásicos Hormonales/farmacología , Neoplasias de la Mama/patología , Estradiol/análogos & derivados , Moduladores de los Receptores de Estrógeno/farmacología , Tamoxifeno/análogos & derivados , Tamoxifeno/farmacología , Membrana Basal/metabolismo , Adhesión Celular/efectos de los fármacos , Colágeno , Combinación de Medicamentos , Estradiol/farmacología , Femenino , Fulvestrant , Humanos , Laminina/metabolismo , Microscopía Electrónica de Rastreo , Microvellosidades/efectos de los fármacos , Invasividad Neoplásica , Metástasis de la Neoplasia , Proteoglicanos , Seudópodos/efectos de los fármacos , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/patología
12.
Clin Exp Metastasis ; 15(4): 393-9, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9219727

RESUMEN

The metastasis of malignant tumor cells to other organs in the body is the major cause of cancer-related patient mortality. Therefore, the inhibition of tumor cell motility is critical in the prevention or control of tumor malignancy. In the present study, the antimetastatic potential of antiestrogens [tamoxifen (TAM); ICI-182,780 (ICI); and Analog II (AII)] on highly invasive, estrogen receptor (ER)-negative MDA-MB-231 (MDA) and non-invasive, ER-positive MCF-7 (MCF) human breast cancer cell lines was investigated using an in vitro wound model. Wounds were created in confluent cell cultures and repopulation of the wound space was evaluated by counting the number of cells that migrated into the wound area and by measuring the maximum distance traveled. In addition, the number of cells that were passively seeded into the wounded area was determined. ICI and AII reduced the number of MCF cells that migrated into the wounded area and reduced the number of viable passively seeded MDA cells. Unlike ICI and AII, TAM appeared to enhance MCF and MDA cell movement. This study indicates that the in vitro wound technique is applicable to the study of breast cancer cell movement in response to antiestrogens and other antimetastatic agents. It also demonstrates that antiestrogens differ in their influence on breast cancer cell migration.


Asunto(s)
Neoplasias de la Mama/patología , Movimiento Celular/efectos de los fármacos , Antagonistas de Estrógenos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Estradiol/análogos & derivados , Estradiol/farmacología , Fulvestrant , Humanos , Invasividad Neoplásica/patología , Receptores de Estrógenos/efectos de los fármacos , Receptores de Estrógenos/metabolismo , Tamoxifeno/análogos & derivados , Tamoxifeno/farmacología , Células Tumorales Cultivadas
13.
Mutat Res ; 386(3): 307-14, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9219568

RESUMEN

Chinese hamster V79 cells and their arsenite-resistant variants were found to have an arsenite- and antimonite-inducible tolerance mechanism which protects against the subsequent cytotoxic effects of arsenate, arsenate and antimonite. Inducible tolerance requires de novo mRNA and protein synthesis, and is independent of the heat shock response. In contrast, we report that the arsenite hypersensitive variant line As/S27D lacks the inducible tolerance response. Numerous attempts were made to detect an inducible tolerance response to arsenite in a variety of human cells. An assay based on Neutral red uptake was used in order to study inducible tolerance in cells with poor clonability. Neither normal diploid cells nor human tumor cells of different origins were found to elicit an inducible tolerance response to arsenite. This finding may help to explain why rodents do not develop tumors after exposure to arsenite, while humans do. In addition, all human cell lines tested were much more sensitive to arsenite compared to Chinese hamster cells. Human keratinocytes were especially sensitive. In general, human cells resemble arsenic hypersensitive Chinese hamster As/R27D cells, which have lost a protective mechanism found in wild-type Chinese hamster cells.


Asunto(s)
Arsénico/toxicidad , Resistencia a Medicamentos , Venenos/toxicidad , Animales , Línea Celular , Cricetinae , Humanos , Especificidad de la Especie
14.
Anticancer Drugs ; 8(10): 964-73, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9436640

RESUMEN

Analog II (1,1-dichloro-cis-2,3-diarylcyclopropane), previously shown to be a pure antiestrogen in mice, was examined for potential antitumor activity on human breast cancer cells in culture. In this study, Analog II produced a dose-related antiproliferative effect on the growth of estrogen receptor (ER)-positive MCF-7 human breast cancer cells over a concentration range of 10(-11) to 10(-5) M. Analog II increased the fraction of MCF-7 cells in the G2/M phase of the cell cycle. Further, this compound inhibited the growth of ER-negative MDA-MB-231 human breast cancer cells over a concentration range of 10(-9) to 10(-6) M. Using scanning electron microscopy to evaluate drug-induced changes in cellular morphology, it was observed that Analog II decreased the length and density of microvilli on both MCF-7 and MDA-MB-231 cells. The effects of Analog II on MCF-7 and MDA-MB-231 cell proliferation and morphology were not reversed in the presence of estradiol. In addition, the induction of estrogen-dependent genes in MCF-7 cells was not reversed by Analog II. It was observed that non-specific cytotoxicity may be responsible for part of the Analog II-induced inhibition on MCF-7 and MDA-MB-231 cell proliferation. However, the antitumor activity of this compound was found to be specific to human breast cancer cells since it did not alter the proliferation or viability of non-breast A-549 human lung cancer cells. In conclusion, these results indicate that Analog II is a potent antitumor agent, has a unique antitumor mechanism in breast cancer cells and may be effective in the treatment of breast cancer.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Antagonistas de Estrógenos/farmacología , Tamoxifeno/análogos & derivados , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Catepsina D/biosíntesis , Catepsina D/genética , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Estradiol/metabolismo , Estradiol/farmacología , Expresión Génica , Humanos , Cinética , Biosíntesis de Proteínas , Proteínas/genética , Receptores de Estrógenos/metabolismo , Tamoxifeno/farmacología , Factor Trefoil-1 , Células Tumorales Cultivadas , Proteínas Supresoras de Tumor
15.
Anticancer Res ; 16(2): 837-42, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8687138

RESUMEN

Tamoxifen, although widely used in the treatment of estrogen-dependent tumors, is a partial estrogen agonist producing undesirable effects in breast cancer patients. ICI 182,780 a steroidal antiestrogen displays pure antagonist activity which is due to its ability to prevent dimerization of the estrogen receptor (ER). Our previous studies have shown that 1,1-dichloro-cis-2,3-diaryl cyclopropane (Analog II), a diarylcyclopropyl compound is devoid of estrogenic activity, has a weak binding affinity for the estrogen receptor in the mouse uterine tissue and inhibits the growth of breast cancer cells in culture. These findings suggest that Analog II may not inhibit tumor cell growth at the cellular level by an ER-mediated mechanism of action. Since these three antiestrogens appear to have different mechanisms of antiestrogenic activity, the purpose of this study was to compare the influence of the three antiestrogens on estradiol-induced expression of pS2 and cathepsin D (cath-D). These genes are known to be primarily under the influence of estrogen in ER positive MCF-7 human breast cancer cells. The results of this study demonstrate different mechanisms of regulation of the cath-D and pS2 genes by antiestrogens in MCF-7 cells. This study indicates that ICI 182,780 is a pure antagonist at the levels of gene regulation and cell proliferation. The relative order of inhibitory action was found to be ICI 182,780 > tamoxifen > Analog II.


Asunto(s)
Neoplasias de la Mama/metabolismo , Catepsina D/metabolismo , Antagonistas de Estrógenos/farmacología , Proteínas de Neoplasias/metabolismo , Proteínas , ARN Mensajero/metabolismo , Catepsina D/genética , Estradiol/análogos & derivados , Estradiol/farmacología , Femenino , Fulvestrant , Expresión Génica/efectos de los fármacos , Humanos , Proteínas de Neoplasias/genética , Tamoxifeno/análogos & derivados , Tamoxifeno/farmacología , Factor Trefoil-1 , Células Tumorales Cultivadas , Proteínas Supresoras de Tumor
16.
Res Commun Mol Pathol Pharmacol ; 89(1): 85-92, 1995 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-7582865

RESUMEN

Tamoxifen, a nonsteroidal antiestrogen is widely used in the treatment of breast cancer. Although clearly of clinical value, it produces adverse side effects associated with its estrogen agonist activity. This has led to the development of antiestrogens with less estrogen agonist activity. Analog II (1,1-dichloro-cis-2,3-diaryl cyclopropane) is a cyclopropyl compound which produces pure antiestrogenic activity in mice and inhibits the proliferation of breast cancer cells. Since the genotoxicity of Analog II has not been examined, the aim of the present study was to investigate the mutagenic potential of Analog II. The mutagenic effects of Analog II were studied at the hypoxanthine phosphoribosyl transferase (hprt) locus in Chinese hamster lung fibroblasts (V79 cell line) and compared to tamoxifen and estradiol. In this study Analog II was not mutagenic at the hprt locus in V79 cells and appeared to have less mutagenic potential than either estradiol or tamoxifen. However, an examination of the genotoxicity of metabolic products of these compounds will be necessary before definite conclusions can be drawn concerning their genotoxicity in vivo.


Asunto(s)
Ciclopropanos/toxicidad , Antagonistas de Estrógenos/toxicidad , Hipoxantina Fosforribosiltransferasa/genética , Mutágenos/toxicidad , Animales , Células Cultivadas , Cricetinae , Cricetulus , Estradiol/toxicidad , Ratones , Tamoxifeno/toxicidad
17.
Toxicol Lett ; 76(1): 71-5, 1995 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7701519

RESUMEN

The objective of the present study was to evaluate the genotoxicity of a combination exposure to lead and smoking in workers from the printing industry and also to examine the possible interaction between the two agents. Individuals were classified into 4 different groups: control group, lead-exposed group, smokers and the double-exposure group. Chromosomal analysis was carried out according to conventional methods. Our preliminary study shows that lead-exposed individuals had a significantly increased frequency of sister chromatid exchanges. Further, double exposure to smoking and lead inhibits mitosis.


Asunto(s)
Plomo/efectos adversos , Exposición Profesional/efectos adversos , Intercambio de Cromátides Hermanas , Fumar/genética , Adulto , Humanos , Masculino , Persona de Mediana Edad , Mutagénesis , Intercambio de Cromátides Hermanas/efectos de los fármacos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA