Showing papers by "Matilde Todaro published in 2005"

NF-κB protects Behçet's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins

Abstract: Objective To determine whether prolongation of the inflammatory reaction in patients with Behcet's disease (BD) is related to apoptosis resistance and is associated with the up-regulation of antiapoptotic factors. Methods The percentage of cell death was evaluated by flow cytometry in peripheral blood mononuclear cells from 35 patients with BD and 30 healthy volunteers. The expression levels of antiapoptotic factors and NF-κB regulatory proteins were measured using Western blotting and immunohistochemical analyses. To down-regulate NF-κB nuclear translocation, BD T lymphocytes were exposed in vitro to thalidomide and subjected to transfection with NF-κB small interfering RNA. Results Although CD95 is highly expressed in BD T cells, the absence of sensitivity to CD95-induced apoptosis observed may be attributable to the inhibitory action of antiapoptotic genes. Immunoblot analysis for major antiapoptotic proteins showed considerable up-regulation of the short form of cellular FLIP (cFLIP) and Bcl-xL in BD activated T cells, while levels of Bcl-2, caspase 3, and caspase 8 in activated T cells from patients with BD were comparable with those in activated T cells from normal donors. Moreover, expression of IKK and IκB was up-regulated, whereas NF-κB translocated to the nucleus in BD T cells, suggesting that NF-κB activation may modulate the expression of antiapoptotic genes. Interestingly, thalidomide and NF-κB small interfering RNA down-regulated cFLIP and Bcl-xL expression levels and sensitized BD activated T cells to CD95-induced apoptosis. Conclusion Taken together, these results indicate that NF-κB contributes to the regulation of the apoptosis-related factors and death receptors leading to apoptosis resistance in BD T cell subsets. Our results suggest that NF-κB plays a crucial role in the pathogenesis of BD, and that its pharmacologic control could represent a key strategy in modulating specific immune-mediated disease.

PED mediates AKT-dependent chemoresistance in human breast cancer cells

Abstract: Killing of tumor cells by cytotoxic therapies, such as chemotherapy or gamma-irradiation, is predominantly mediated by the activation of apoptotic pathways. Refractoriness to anticancer therapy is often due to a failure in the apoptotic pathway. The mechanisms that control the balance between survival and cell death in cancer cells are still largely unknown. Tumor cells have been shown to evade death signals through an increase in the expression of antiapoptotic molecules or loss of proapoptotic factors. We aimed to study the involvement of PED, a molecule with a broad antiapoptotic action, in human breast cancer cell resistance to chemotherapeutic drugs-induced cell death. We show that human breast cancer cells express high levels of PED and that AKT activity regulates PED protein levels. Interestingly, exogenous expression of a dominant-negative AKT cDNA or of PED antisense in human breast cancer cells induced a significant down-regulation of PED and sensitized cells to chemotherapy-induced cell death. Thus, AKT-dependent increase of PED expression levels represents a key molecular mechanism for chemoresistance in breast cancer.

Method for the purification and amplification of tumoral stem cells

Abstract: The invention concerns a method for the purification and amplification in the undifferentiated state of tumoral stem cells from solid tumours which are most resistant to conventional therapies, aiming at devising new tumour markers and therapeutic targets both for early diagnosis and for targeted therapeutic strategies.

Osservazioni a proposito di un caso di cisti gigante della milza

Abstract: The Authors, on the basis of a case of giant spleen cyst with positive tumoral markers, analyse some epidemiological and clinical aspects related to splenic non parasitic cysts. They affirm the priority of the conservative surgery, whenever possible, followed by an appropriate follow-up, although in this case their therapeutic choice was radical, due to the lack of residual parenchyma. In accordance with the data of several publications, as well as on the basis of the results obtained, the conservative approaches have been revaluated, above all in view of the modern findings related to the function of the spleen. The conservative approach cannot be carried out in the following cases: neoplastic diseases, increase of the tumoral markers serum levels, total involvement of the splenic parenchyma by cysts.