RESUMEN
The famous α-Fe active sites in Fe-zeolites have recently been revealed to correspond to mononuclear high-spin iron(ii) centres in square planar coordination environments. Here we report a first iron siloxide complex which represents a faithful structural and spectroscopic model of such sites. Notably, also an allogon with a distorted structure exists and could be crystallised.
RESUMEN
Classical Hodgkin lymphoma (cHL) is a distinct malignancy of the immune system. Despite the progress made in the understanding of the biology of cHL, the transforming events remain to be elucidated. Recently, we demonstrated that the Janus kinase inhibitor AG490 blocked cellular proliferation and STAT3 phosphorylation in cHL. To explore the potential of constitutively activated STAT3 as a drug target and its role in cHL pathogenesis, different cHL cell lines were analyzed. Treatment of cHL cells by the protein tyrosine kinase inhibitor AG17 was associated with inhibition of cellular proliferation and cell cycle arrest. AG17 treatment was accompanied by decreased levels of STAT3 phosphorylation, whereas NF-kappaB and p38/SAPK2 signaling were not inhibited. Incubation with AG17 or AG490 sensitized cHL cells to CD95/Fas/Apo-1 or staurosporine-mediated apoptosis. Coincubation of tyrphostins with staurosporine was accompanied by rapid complete inhibition of STAT3 phosphorylation. RNA interference directed against STAT3 in L428 and L1236 cHL cells demonstrated that STAT3 is essential for cell proliferation of these cHL cells. In conclusion, these findings support the concept that STAT3 signaling is important in the pathogenesis of cHL and tyrphostins are agents for developing new therapeutic strategies.
Asunto(s)
Apoptosis/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Enfermedad de Hodgkin/tratamiento farmacológico , Transactivadores/metabolismo , Tirfostinos/farmacología , División Celular/efectos de los fármacos , Proteínas de Unión al ADN/genética , Inhibidores Enzimáticos/farmacología , Expresión Génica , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/patología , Humanos , Células Jurkat , Nitrilos , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , ARN Interferente Pequeño , Factor de Transcripción STAT3 , Transducción de Señal/efectos de los fármacos , Estaurosporina/farmacología , Transactivadores/genética , Receptor fas/metabolismoRESUMEN
The MDM2 proto-oncogene encodes a 90-kDa protein that binds to and inactivates the tumor suppressor p53. Several reports describe the presence of different alternatively, as well as, aberrantly spliced transcripts of the MDM2 mRNA in a variety of human cancers that have lost the ability to bind p53. Due to the transforming ability of at least some of the isoforms it has been suggested that they might contribute to tumorigenesis. Here we show that shorter MDM2 transcripts are also widely expressed in normal tissues, including lung and renal tissue, and in lymphocytes. Alteration in MDM2 RNA transcripts were found in the majority of the samples. Although we cannot exclude that alterations in MDM2 preferentially occur during cancer development, our data rather indicate that in this context the commonly observed transcript variants may also possess a normal physiological function.