RESUMEN
BACKGROUND: The cytostatic effects of the polyphenol curcumin and Viscum album extract (VAE) were assessed in soft-tissue sarcoma (STS) cells. METHODS: Eight human STS cell lines were used: fibrosarcoma (HT1080), liposarcoma (SW872, T778, MLS-402), synovial sarcoma (SW982, SYO1, 1273), and malignant fibrous histiocytoma (U2197). Primary human fibroblasts served as control cells. Cell proliferation, viability, and cell index (CI) were analyzed by BrdU assay, MTT assay, and real-time cell analysis (RTCA). RESULTS: As indicated by BrdU and MTT, curcumin significantly decreased the cell proliferation of five cell lines (HT1080, SW872, SYO1, 1273, and U2197) and the viability of two cell lines (SW872 and SW982). VAE led to significant decreases of proliferation in eight cell lines (HT1080, SW872, T778, MLS-402, SW982, SYO1, 1293, and U2197) and reduced viability in seven STS lines (HT1080, SW872, T778, MLS-402, SW982, SYO1, and 1273). As indicated by RTCA for 160 h, curcumin decreased the CI of all synovial sarcoma cell lines as well as T778 and HT1080. VAE diminished the CI in most of the synovial sarcoma (SW982, SYO1) and liposarcoma (SW872, T778) cell lines as well as HT1080. Primary fibroblasts were not affected adversely by the two compounds in RTCA. CONCLUSION: Curcumin and VAE can inhibit the proliferation and viability of STS cells.
Asunto(s)
Curcumina/farmacología , Extractos Vegetales/farmacología , Sarcoma/tratamiento farmacológico , Viscum album/química , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colorimetría , HumanosRESUMEN
Prion protein and prion-like proteins share a number of characteristics. From the molecular point of view, they are constitutive proteins that aggregate following conformational changes into insoluble particles. These particles escape the cellular clearance machinery and amplify by recruiting the soluble for of their constituting proteins. The resulting protein aggregates are responsible for a number of neurodegenerative diseases such as Creutzfeldt-Jacob, Alzheimer, Parkinson and Huntington diseases. In addition, there are increasing evidences supporting the inter-cellular trafficking of these aggregates, meaning that they are "transmissible" between cells. There are also evidences that brain homogenates from individuals developing Alzheimer and Parkinson diseases propagate the disease in recipient model animals in a manner similar to brain extracts of patients developing Creutzfeldt-Jacob's disease. Thus, the propagation of protein aggregates from cell to cell may be a generic phenomenon that contributes to the evolution of neurodegenerative diseases, which has important consequences on human health issues. Moreover, although the distribution of protein aggregates is characteristic for each disease, new evidences indicate the possibility of overlaps and crosstalk between the different disorders. Despite the increasing evidences that support prion or prion-like propagation of protein aggregates, there are many unanswered questions regarding the mechanisms of toxicity and this is a field of intensive research nowadays.
Asunto(s)
Proteínas del Tejido Nervioso/química , Enfermedades Neurodegenerativas/metabolismo , Enfermedades por Prión/metabolismo , Agregación Patológica de Proteínas/metabolismo , Envejecimiento , Enfermedad de Alzheimer/prevención & control , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Animales , Autofagia , Biopolímeros , Ensayos Clínicos Fase II como Asunto , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Endocitosis , Humanos , Cuerpos de Inclusión/química , Cuerpos de Inclusión/patología , Ratones , Enfermedades Neurodegenerativas/patología , Ovillos Neurofibrilares/química , Ovillos Neurofibrilares/patología , Placa Amiloide/química , Placa Amiloide/patología , Polisacáridos/uso terapéutico , Enfermedades por Prión/patología , Enfermedades por Prión/veterinaria , Priones/química , Agregación Patológica de Proteínas/patología , Conformación Proteica , SolubilidadRESUMEN
To establish precise diagnostic algorithms and standardised treatment of sarcomas in specialized centers, the interdisciplinary research group KoSar (sarcoma competence network) has been funded by German Cancer Aid. A sarcoma tissue repository and a diagnostic reference center have been set up, presently containing about 1000 accurately diagnosed sarcomas of different entities. Significant gene expression profiles for synovial sarcomas, leiomyosarcomas, myxoid liposarcomas and a small profile for myxofibrosarcomas as well as a new classification of angiosarcomas were defined. We systematically searched for activated signal transduction pathways in sarcoma cell lines and xenograft transplant models and candidate targets for molecular therapies were identified. Based on these results first clinical studies have been initiated by the German Interdisciplinary Sarcoma Study Group (GISG).
Asunto(s)
Sarcoma/genética , Sarcoma/patología , Animales , Investigación Biomédica , Línea Celular Tumoral , Conducta Cooperativa , Evaluación Preclínica de Medicamentos , Fibrosarcoma/diagnóstico , Fibrosarcoma/tratamiento farmacológico , Fibrosarcoma/genética , Fibrosarcoma/patología , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Comunicación Interdisciplinaria , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/tratamiento farmacológico , Leiomiosarcoma/genética , Leiomiosarcoma/patología , Liposarcoma Mixoide/diagnóstico , Liposarcoma Mixoide/tratamiento farmacológico , Liposarcoma Mixoide/genética , Liposarcoma Mixoide/patología , Técnicas de Diagnóstico Molecular , Terapia Molecular Dirigida , Trasplante de Neoplasias , Sarcoma/diagnóstico , Sarcoma/tratamiento farmacológico , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/tratamiento farmacológico , Sarcoma Sinovial/genética , Sarcoma Sinovial/patología , Transducción de Señal/genéticaRESUMEN
[structure: see text] The stereoselectivity of N-methylputrescine (3) oxidation to pyrrolinium ion 4 in Erythroxylum coca during cocaine (1) biosynthesis was studied. The remote isotope method was used to advantage. Each enantiomer of 4-monodeuterated N-methylputrescine served as a precursor for plant feeding. To facilitate mass-spectrometric analysis of products, a 2H3 13C-methyl group was also incorporated into the 4-deuterio-N-methylputrescines. Oxidative deamination of N-methylputrescine was found to be stereoselective; the pro-S hydrogen atom is removed with 6-10:1 selectivity.