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See detailS-acetyl-glutathione selectively induces apoptosis in human lymphoma cells through a GSH-independent mechanism
Locigno, Roberto; Pincemail, Joël ULg; Henno, Audrey et al

in International Journal of Oncology (2002), 20(1), 69-75

Reduced apoptosis is associated to cancer development. Agents able to restore the programmed cell death responsiveness of cancer cells are foreseen as potential effective cancer therapies. In this study ... [more ▼]

Reduced apoptosis is associated to cancer development. Agents able to restore the programmed cell death responsiveness of cancer cells are foreseen as potential effective cancer therapies. In this study, we report that a glutathione-S-derivative, S-acetyl-glutathione (Sag), induces significant apoptosis in three human lymphoma cell lines, including Daudi, Raji and Jurkat cells while it had no or little effect on either Hut-78 lymphoma cells or the normal BT lymphocytes. We used Annexin-V FACS analysis and DNA laddering to demonstrate that Sag activated apoptosis in the three sensitive cell lines in a dose- and time-dependent-fashion. Using mercury orange staining and FACS analysis, we showed that Sag generated an intracellular GSH depletion in Daudi, Raji and Jurkat cells but not in Hut-78 or the normal BT cells. These data provide direct evidence that Sag specifically activates programmed cell death in lymphoma cells through, at least in part, a depletion of intracellular GSH rather than an increase, as previously suggested. Because of its selective effect on cancer cells, Sag appears as a promising new lymphoma cell apoptosis inducer with potential clinical value for lymphoma patients. [less ▲]

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See detailSodium butyrate and trichostatin A induce growth arrest and apoptosis in breast cancer cells while normal breast epithelial cells are unaffected
Locigno, Roberto; Waltregny, David ULg; Verheyen, Véronique et al

Conference (2001, January)

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See detailSodium butyrate and trichostatin-a induce apoptosis in human breast cancer cells but not in normal human mammary epithelial cells
Locigno, Roberto; Henno, Audrey ULg; Waltregny, David ULg et al

in Proceedings of the American Association for Cancer Research (2001), 42

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See detailTnp-470, a Potent Angiogenesis Inhibitor, Amplifies Human T Lymphocyte Activation through an Induction of Nuclear Factor-Kappab, Nuclear Factor-at, and Activation Protein-1 Transcription Factors
Locigno, Roberto; Antoine, Nadine ULg; Bours, Vincent ULg et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (2000), 80(1), 13-21

TNP-470, an angiogenesis inhibitor derived from fumagillin, is foreseen as a promising anti-cancer drug. Its effectiveness to restrain tumor growth and its lack of major side effects have been ... [more ▼]

TNP-470, an angiogenesis inhibitor derived from fumagillin, is foreseen as a promising anti-cancer drug. Its effectiveness to restrain tumor growth and its lack of major side effects have been demonstrated in several animal models and have led the drug to reach phase III clinical trials. Beside its antiangiogenesis activities, TNP-470 exhibits several effects on the immune system. We had shown previously that TNP-470 stimulated B lymphocyte proliferation through an action on T cells. In this study, we examined the cellular and molecular modifications induced by TNP-470 in normal human T lymphocytes. Transmission electron microscopic examination of PHA/TNP-470-treated T cells revealed significant morphologic modifications when compared with PHA-treated control T cells. TNP-470 induced indeed an important and significant increase of the nuclear size as well as major nuclear chromatin decondensation. This observation indicated that TNP-470 amplified T-cell activation and led us to investigate its effects on the activation of transcription factors involved in T-cell activation. Using electrophoretic mobility shift assays, we have demonstrated that TNP-470 amplifies and extends the DNA-binding activity of nuclear factor-AT, nuclear factor-KB, and activation protein-1 in T cells. Furthermore, the angioinhibin significantly increased the secretion of IL-2 and IL-4. Our data demonstrate that TNP-470 amplifies the activation of T cells. This effect, whose molecular mechanisms remain to be elucidated, has to be taken into account in the assessment of the antitumor effect of the drug. [less ▲]

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