Browsing by Author "Maksimovic-Ivanic, Danijela (6507584634)"

The immunomodulatory potential of tiazofurin (TR) on experimental autoimmune encephalomyelitis (EAE) was investigated. Given continuously, TR dose-dependently suppressed the development of EAE in Dark Agouti (DA) rats immunized with either rat spinal cord homogenate (SCH) or myelin oligodendrocyte glycoprotein (MOG). Amelioration of clinical signs was also obtained when the drug was administered during the inductive phase only (day 0 to 8), or during the effector phase (day 10 to 20) of the disease. Efficacy of TR was further evaluated by adoptive transfer of the disease with myelin basic protein (MBP)-sensitized draining lymph node cells (DLNC). Cells from TR-protected rats failed to transfer the disease into naive syngeneic recipients; in addition, TR treatment of recipient rats that had received MBP-sensitized lymphoid cells diminished the adoptively transferred EAE. A reduction of clinical EAE in TR-treated rats was accompanied with the absence of mononuclear infiltration in the spinal cord and defective adhesive cell-cell interactions. The anti-MOG autoAb production was also decreased. Importantly, no evidence for a generalized impairment of the T cell activity, nor decreased in vitro proliferative antigen specific response of LNC from TR-treated animals was found. These results suggest that TR exerts its EAE protective and suppressive effects by limiting adhesive interactions involved in the autoimmune pathogenic process, and due to the lack of general immunosuppressive activity, it should be considered as a candidate drug for the treatment of neuroinflammatory diseases like multiple sclerosis (MS). © 2002 Elsevier Science B.V. All rights reserved.

The immunomodulatory potential of tiazofurin (TR) on experimental autoimmune encephalomyelitis (EAE) was investigated. Given continuously, TR dose-dependently suppressed the development of EAE in Dark Agouti (DA) rats immunized with either rat spinal cord homogenate (SCH) or myelin oligodendrocyte glycoprotein (MOG). Amelioration of clinical signs was also obtained when the drug was administered during the inductive phase only (day 0 to 8), or during the effector phase (day 10 to 20) of the disease. Efficacy of TR was further evaluated by adoptive transfer of the disease with myelin basic protein (MBP)-sensitized draining lymph node cells (DLNC). Cells from TR-protected rats failed to transfer the disease into naive syngeneic recipients; in addition, TR treatment of recipient rats that had received MBP-sensitized lymphoid cells diminished the adoptively transferred EAE. A reduction of clinical EAE in TR-treated rats was accompanied with the absence of mononuclear infiltration in the spinal cord and defective adhesive cell-cell interactions. The anti-MOG autoAb production was also decreased. Importantly, no evidence for a generalized impairment of the T cell activity, nor decreased in vitro proliferative antigen specific response of LNC from TR-treated animals was found. These results suggest that TR exerts its EAE protective and suppressive effects by limiting adhesive interactions involved in the autoimmune pathogenic process, and due to the lack of general immunosuppressive activity, it should be considered as a candidate drug for the treatment of neuroinflammatory diseases like multiple sclerosis (MS). © 2002 Elsevier Science B.V. All rights reserved.

Covalent attachment of NO to the first approved HIV protease inhibitor Saquinavir (Saq-NO) expands the therapeutic potential of the original drug. Apart from retained antiviral activity, the modified drug exerts strong antitumor effects and lower toxicity. In the present study, we have evaluated the sensitivity of different hematological malignancies to Saq-NO. Saq-NO efficiently diminished the viability of Jurkat, Raji, HL-60 and K562 cells. While Jurkat and Raji cells (established from pediatric patients) displayed abrogated proliferative potential, HL-60 and K652 cells (originated from adults) exposed to Saq-NO treatment underwent caspase dependent apoptosis. In addition, similar sensitivity to Saq-NO was observed in mononuclear blood cells obtained from pediatric patients with acute lymphoblastic leukemia (ALL) and adult patients with acute myeloid leukemia (AML). Western blot analysis indicated p70S6 kinase as a possible intracellular target of Saq-NO action. Moreover, the addition of a NO moiety to Lopinavir resulted in improved antitumor potential as compared to the parental compound, suggesting that NO-derived HIV protease inhibitors are a potential new source of anticancer drugs with unique mode of action. © 2015 Elsevier Ltd.

Covalent attachment of NO to the first approved HIV protease inhibitor Saquinavir (Saq-NO) expands the therapeutic potential of the original drug. Apart from retained antiviral activity, the modified drug exerts strong antitumor effects and lower toxicity. In the present study, we have evaluated the sensitivity of different hematological malignancies to Saq-NO. Saq-NO efficiently diminished the viability of Jurkat, Raji, HL-60 and K562 cells. While Jurkat and Raji cells (established from pediatric patients) displayed abrogated proliferative potential, HL-60 and K652 cells (originated from adults) exposed to Saq-NO treatment underwent caspase dependent apoptosis. In addition, similar sensitivity to Saq-NO was observed in mononuclear blood cells obtained from pediatric patients with acute lymphoblastic leukemia (ALL) and adult patients with acute myeloid leukemia (AML). Western blot analysis indicated p70S6 kinase as a possible intracellular target of Saq-NO action. Moreover, the addition of a NO moiety to Lopinavir resulted in improved antitumor potential as compared to the parental compound, suggesting that NO-derived HIV protease inhibitors are a potential new source of anticancer drugs with unique mode of action. © 2015 Elsevier Ltd.