1,721,029 research outputs found
The soluble ectodomain of Ret C634Y inhibits both the wild type and the constitutively active Ret.
No full textNucleic acids delivering nucleic acids.
No full textNucleic acid therapeutics, including siRNAs, miRNAs/antimiRs, gRNAs and ASO, represent innovative and highly promising molecules for the safe treatment of a wide range of pathologies. The efficiency of systemic treatments is impeded by 1) the need to overcome physical and functional barriers in the organism, and 2) to accumulate in the intracellular active site at therapeutic concentrations. Although oligonucleotides either as modified naked molecules or complexed with delivery carriers have revealed to be effectively delivered to the affected target cells, this is restricted to topic treatments or to a few highly vascularized tissues. Therefore, the development of effective strategies for therapeutic nucleic acid selective delivery to target tissues is of primary importance in order to reduce the occurrence of undesired effects on non-target healthy tissues and to permit their translation to clinic. Due to their high affinity for specific ligands, high tissue penetration and chemical flexibility, short single-stranded nucleic acid aptamers are emerging as very attractive carriers for various therapeutic oligonucleotides. Yet, different aptamer-based bioconjugates, able to provide accumulation into target tissues, as well as efficient processing of therapeutic oligonucleotides, have been developed. In this respect, nucleic acid aptamer-mediated delivery strategies represent a powerful approach able to increase the therapeutic efficacy also highly reducing the overall toxicity. In this review, we will summarize recent progress in the field and discuss achieved objectives and optimization of aptamers as delivery carriers of short oligonucleotides
The soluble ectodomain of Ret C634Y inhibits both the wild type and the constitutively active Ret.
No full textThe soluble ectodomain of Ret C634Y inhibits both the wild type and the constitutively active Ret.
No full textPreferential expression of the dbl protooncogene in some tumors of neuroectodermal origin.
No full textWe have investigated the expression of the dbl protooncogene in a wide variety of human tumors of different embryological derivation. We found that proto-dbl mRNA could be detected preferentially in a few neoplastic histiotypes of neuroectodermal origin. The common, normal 5-kilobase size of the proto-dbl transcript detected indicated that the proto-dbl in these tumors was not rearranged. These data, in agreement with our previous reports, suggest that the dbl protooncogene is expressed in a highly tissue-specific manner and indicate that this gene may be involved in the growth and differentiation of some cells of neuroectodermal origin
The Shp-1 and Shp-2, tyrosine phosphatases, are recruited on cell membrane in two distinct molecular complexes including Ret oncogenes.
No full textThe Shp-2 and Shp-1 non-transmembrane tyrosine phosphatases display different and even opposing effects on downstream signaling events initiated by Ret activation. By using rat pheochromocytoma-derived PC12 cells, here we studied the interactions of Shp-2 and Shp-1 with two activated mutants of Ret receptor, Ret(C634Y) and Ret(M918T). Each of these mutated receptors causes inheritance of distinct cancer syndromes, multiple endocrine neoplasia (MEN) type 2A and type 2B, respectively. We show that: (i) both Shp-1 and Shp-2 are associated to a multiprotein complex that includes Ret mutants; (ii) the Shp-1-Ret complexes are distinct from Shp-2-Ret complexes, and these complexes are differently distributed inside and outside lipid rafts; (iii) constitutively activated Ret proteins neither directly bind to nor are substrates of these phosphatases. Our results well support the evidence that Ret complexes within and outside rafts mediate distinct biological functions, and indicate that the presence of either Shps participates to determine such functions
Preferential Expression of the dbl Protooncogene in Some Tumors of Neuroectodermal Origin
No full textWe have investigated the expression of the dbl protooncogene in a wide variety of human tumors of different embryological derivation. We found that proto-dbl mRNA could be detected preferentially in a few neoplastic histiotypes of neuroectodermal origin. The common, normal 5-kilobase size of the proto-dbl transcript detected indicated that the proto-dbl in these tumors was not rearranged. These data, in agreement with our previous reports, suggest that the dbl protooncogene is expressed in a highly tissue-specific manner and indicate that this gene may be involved in the growth and differentiation of some cells of neuroectodermal origin.We have investigated the expression of the dbl protooncogene in a wide variety of human tumors of different embryologicai derivation. We found that proio-dbl mRNA could be detected preferentially in a few neoplastic histiotypes of neuroectodermal origin. The common, normal 5-kilobase size of the proto-dbl transcript detected indicated that the proto-dbl in these tumors was not rearranged. These data, in agreement with our previous reports, suggest that the dbl protooncogene is expressed in a highly tissue-specific manner and indicate that this gene may be involved in the growth and differentiation of some cells of neuroectodermal origin. © 1991, American Association for Cancer Research. All rights reserved
Shp2 in PC12 cells: NGF versus EGF signalling.
No full textThe balance between specific signals from different growth factors dictates the biological response of mammalian cells including cell proliferation, differentiation and survival. PC12 cells represent a model of choice to compare the signalling of differentiative growth factors, as NGF, and of mitogenic growth factors, as EGF. In these cells the prolonged activity of the ERK kinase dictates the decision of cells to differentiate. Here we focused on the cytosolic tyrosine phosphatase Shp2 as an established regulator of the Ras-ERK cascade, to elucidate its involvement in determining the stimulation-dependent PC12 cell fate. To this end, we generated PC12 derived cell lines that express the interfering mutant of Shp2 under a tetracycline-inducible promoter. Our findings show that Shp2 participates to the opposite effects induced in PC12 cells by EGF and NGF and that the interactions with the multidocking Gab2 protein mediate such effects
Effect of cytidine analogs on cell growth and differentiation on a human neuroblastoma line.
No full textThe cytidine analog 5-AZA-2'-deoxycytidine (5-AZA-CdR) has been demonstrated to induce cellular differentiation; on the other hand, induction of differentiation has been suggested as a possible form of therapy for leukemic cells. We have evaluated the possibility that the neuroblastoma malignant tumor growth could be controlled by treatment that promotes the differentiation of immature tumor cells. We have previously reported on differentiation of murine neuroblastoma cells (41A3) treated with 5-AZA-CdR. In this paper, we describe the effect of 5-AZA-CdR on human neuroblastoma cell line CHP-100. The drug-treated cells show some degree of differentiation, demonstrated by morphological and biochemical markers. A significant DNA hypomethylation and partial inhibition of DNA synthesis and cell proliferation is also observed. This effect is more stable than that caused by another cytidine analog, Cytosine-beta-D-Arabinofuranoside (ARA-C)
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