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1.
J Biol Regul Homeost Agents ; 27(1): 105-19, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23489691

RESUMEN

Breast cancer is a leading cancer in women and despite the benefits of the current therapies a significant number of patients with this tumor is at risk of relapse. Some of the alterations taking place in breast cancer cells are currently exploited by molecularly targeted drugs. Different drugs have been developed which target a single molecule but, given that the tumor originates from the dysregulation of many genes, there is the need to find new drugs that have more than one molecular target. Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] (CUR), a polyphenolic compound found in the spice turmeric, is a pleiotropic molecule able to interact with a variety of molecular targets and has antitumor, anti-inflammatory, antioxidant, immunomodulatory and antimicrobial activities. Here we demonstrate that CUR inhibits the growth of breast cancer cell lines in a dose dependent manner, with IC50 values in the micromolar range, and induces an increase in the percentage of cells in sub-G0 phase, representing the apoptotic cell population. The activation of apoptosis was confirmed by PARP-1 cleavage and by the increased ratio between the pro-apoptotic Bax and the anti-apoptotic Bcl-2 protein. In addition, in CUR-treated cells the activity of ERK1/ERK2 MAP kinases was down-regulated. The cytotoxic effects of CUR were observed in breast cancer cells expressing either high or low levels of ErbB2/neu. The in vivo antitumor activity of CUR was tested in BALB-neuT mice transgenic for the neu oncogene, which develop atypical hyperplasia of the mammary gland at 6 weeks of age and invasive carcinoma at 16 weeks of age. CUR, administered to mice both early and in an advanced stage of mammary carcinogenesis, induced a significant prolongation of tumor-free survival and a reduction of tumor multiplicity. In addition, CUR administration was safe, since no modification of hematological and clinical chemistry parameters could be observed in BALB-neuT and BALB/c mice treated with this compound for several weeks. These findings support further studies on the therapeutic potential of CUR in combination with standard therapies in breast cancer patients.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Curcumina/farmacología , Neoplasias Mamarias Animales/patología , Receptor ErbB-2/metabolismo , Animales , Neoplasias de la Mama/tratamiento farmacológico , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Curcumina/efectos adversos , Curcumina/uso terapéutico , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neoplasias Mamarias Animales/sangre , Neoplasias Mamarias Animales/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Células 3T3 NIH , Fosforilación/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Ratas , Receptor ErbB-2/genética , Proteína X Asociada a bcl-2/metabolismo
2.
J Neurol ; 232(2): 109-11, 1985.
Artículo en Inglés | MEDLINE | ID: mdl-4020389

RESUMEN

A patient with post-thyroidectomy hypoparathyroidism, basal ganglia calcification, parkinsonism and seizures is reported. The parkinsonism was resistant to levodopa therapy but was not significantly improved by the correction of hypoparathyroidism. Previously reported cases are discussed, as well as the relationship between hypoparathyroidism, calcification of basal ganglia, parkinsonism and epilepsy.


Asunto(s)
Enfermedades de los Ganglios Basales/etiología , Calcinosis/etiología , Epilepsia/etiología , Hipoparatiroidismo/complicaciones , Enfermedad de Parkinson/etiología , Enfermedades de los Ganglios Basales/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Femenino , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias , Tiroidectomía , Factores de Tiempo , Tomografía Computarizada por Rayos X
3.
Eur Neurol ; 24(4): 262-71, 1985.
Artículo en Inglés | MEDLINE | ID: mdl-4006995

RESUMEN

The acute effects of intravenously administered L-acetylcarnitine (L-AC) were evaluated in 5 healthy and 20 diseased volunteers (17 vascular, 3 tumoral cerebral lesions). Short-latency scalp somatosensory-evoked potentials (SEPs) to simultaneous median, and separate unilateral peroneal nerve stimulation were carried out before and after L-AC administration (at 10-, 30- and 60-min intervals). L-AC did not influence peak and interpeak latencies; however, in a percentage of healthy and diseased volunteers a clear-cut amplitude increase was evident affecting all those peaks generated between the thalamus and the cortex. While in normal and tumoral volunteers the voltage increase was bilaterally balanced, the amplitude increments were more evident on the 'affected' hemisphere in vascular patients, partially reversing the abnormal amplitude ratios between homologous peaks on 'healthy' and 'affected' hemispheres. In no case were transient clinical changes, either of an objective or subjective nature, associated with SEP amplitude changes; these were still present at the 60th minute, having reached their nadir at the 30th minute in 'responders'.


Asunto(s)
Acetilcarnitina/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Carnitina/análogos & derivados , Trastornos Cerebrovasculares/tratamiento farmacológico , Potenciales Evocados Somatosensoriales , Adulto , Anciano , Neoplasias Encefálicas/fisiopatología , Corteza Cerebral/fisiopatología , Trastornos Cerebrovasculares/fisiopatología , Femenino , Humanos , Masculino , Nervio Mediano/fisiopatología , Persona de Mediana Edad , Vías Nerviosas/fisiopatología , Sensación/fisiología , Tálamo/fisiopatología
4.
Surg Neurol ; 15(2): 128-34, 1981 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-6264637

RESUMEN

Twenty-five adults with recurrent supratentorial malignant gliomas were treated with VM-26 in a monochemotherapy schedule, the antiblastic region covering a period of 24 weeks. Five cases were excluded from the final evaluation, 4 because of protocol violations and 1 due to intolerance to the drug. In the group of 20 patients who met the criteria for evaluation, 7 (35%) showed a partial or complete response, with clinical or radiological tumor aggression, and the conditions of 7 (35%) were unchanged at the end of the chemotherapy courses. The progression-free intervals turned out to be 10.4 months and 8.5 months, respectively. Six patients (30%) complained of tumor progression despite the treatment. Most of the patients are still alive, and the actuarial survival rate is encouraging. Toxicity was mainly hematologic, but usually moderate and easily reversible.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Podofilotoxina/análogos & derivados , Tenipósido/uso terapéutico , Anemia/inducido químicamente , Astrocitoma/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas , Femenino , Glioblastoma/tratamiento farmacológico , Humanos , Enfermedades Renales/inducido químicamente , Masculino , Oligodendroglioma/tratamiento farmacológico , Tenipósido/efectos adversos
5.
Childs Brain ; 8(2): 107-18, 1981.
Artículo en Inglés | MEDLINE | ID: mdl-7018855

RESUMEN

A 5-year experience of the multidisciplinary treatment of pediatric medulloblastoma with the SIOP (International Society of Pediatric Oncology) trial is presented. 33 eligible patients finally reduced to a total of 30 evaluative cases were treated with major surgical resection, extensive irradiation, and combined chemotherapy (vincristine + CCNU). The overall survival rate without recurrence was encouraging, and the actuarial survival rate is satisfactory. At follow-up controls, most of the patients showed a good performance status and a promising neurological stage. However, the problem concerning quality of life remains unsolved: morbidity and sequelae following high-dose radiotherapy and concomitant antiblastic treatment were noticeable.


Asunto(s)
Neoplasias Cerebelosas/terapia , Meduloblastoma/terapia , Adolescente , Neoplasias Cerebelosas/mortalidad , Niño , Preescolar , Ensayos Clínicos como Asunto , Quimioterapia Combinada , Femenino , Humanos , Lactante , Lomustina/administración & dosificación , Masculino , Meduloblastoma/mortalidad , Cuidados Posoperatorios , Pronóstico , Vincristina/administración & dosificación
6.
J Anal Toxicol ; 4(6): 293-8, 1980.
Artículo en Inglés | MEDLINE | ID: mdl-7206659

RESUMEN

A GLC assay for phencyclidine (PCP) is described, which also simultaneously measures three primary hydroxylated metabolites formed from incubating PCP in tissue homogenates. Using the FID detector, the limits of reliable detection of PCP and both monohydroxy metabolites, 4-phenyl-4-piperidino-cyclohexanol, 2, and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine, 3, are 0.02 mumol per injection and 0.05 mumol for the dihydroxy metabolite, 4-(4'-hydroxypiperidino)-4-phenylcyclohexanol, 2A. Baseline separation of an compounds was achieved and coefficients of variation (between-run) was 3-6% for PCP, and both monohydroxy metabolites, and 12% for the dihydroxy metabolite. A GCMS assay is also reported herein for the analysis of PCP at low levels, and can detect 5 pmol per injection of PCP, with a linear standard curve from 50 to 2000 pmol.


Asunto(s)
Fenciclidina/análisis , Animales , Biotransformación , Cromatografía de Gases/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Masculino , Fenciclidina/metabolismo , Conejos
7.
Ann Ophthalmol ; 11(1): 94-8, 1979 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-420481

RESUMEN

Cysts of Rathke's cleft are considered as benign lesions, a practically permanent cure of which can be achieved by aspiration of the fluid content and ample opening of the capsule. The case of a patient who suffered from a recurrence of the cyst, 13 years after a first operation carried out according to such surgical criteria, is reported in order to signal the actual possibility of recurrence of such lesions.


Asunto(s)
Craneofaringioma/complicaciones , Hemianopsia/etiología , Recurrencia Local de Neoplasia/complicaciones , Adenohipófisis , Neoplasias Hipofisarias/complicaciones , Escotoma/etiología , Adulto , Ceguera/etiología , Craneofaringioma/diagnóstico , Craneofaringioma/cirugía , Femenino , Estudios de Seguimiento , Humanos , Recurrencia Local de Neoplasia/diagnóstico , Atrofia Óptica/etiología , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/cirugía , Succión
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