The concept of pH-sensitive liposomes has been applied to the delivery of an oligonucleotide comp... more The concept of pH-sensitive liposomes has been applied to the delivery of an oligonucleotide complementary to the AUG region of the env mRNA of the Friend retrovirus. The oligonucleotide-containing liposomes were prepared by using the reverse phase evaporation or the freeze-thawing methodology. They were characterized for oligonucleotide entrapment efficiency, size, oligonucleotide release at different pH and stability. Optimisation of the
The Ras-Raf-MEK-ERK1/2 signaling pathway regulates fundamental processes in malignant cells. Howe... more The Ras-Raf-MEK-ERK1/2 signaling pathway regulates fundamental processes in malignant cells. However, the exact contributions of MEK1 and MEK2 to the development of cancer remain to be established. We studied the effects of MEK small-molecule inhibitors (PD98059 and U0126) and MEK1 and MEK2 knock-down on cell proliferation, apoptosis and MAPK activation. We showed a diminution of cell viability that was associated with a downregulation of cyclin D1 expression and an increase of apoptosis marker in MEK2 silenced cells; by contrast, a slight increase of cell survival was observed in the absence of MEK1 that correlated with an augment of cyclin D1 expression. These data indicate that MEK2 but not MEK1 is essential for MDA-MB-231 cell survival. Importantly, the role of MEK2 in cell survival appeared independent on ERK1/2 phosphorylation since its absence did not alter the level of activated ERK1/2. Indeed, we have reported an unrevealed link between MEK2 and MKK3/MKK6-p38 MAPK axis wher...
To stuck the effect of chemotherapy on parasite-macrophage interaction we used the wild-type Y st... more To stuck the effect of chemotherapy on parasite-macrophage interaction we used the wild-type Y strain (drug-susceptible) of Trypanosoma cruzi and a drug-resistant parasite population derived from the same strain. Trypomastigotes isolated from untreated infected mice, as well as, 3 h after treatment with BZ were incubated with inflammatory macrophages and used to study phagocytosis, parasite destruction, cytokine release and reactive nitrogen intermediates (RN!) synthesis. Phagocytosis and destruction of the drug-susceptible parasites were significant/v enhanced by drug treatment. These enhancements were accompanied by an increase in cytokines [interleukin (IL)-12 and tumour necrosis factor (TNF)alpha] and RNI release by murine inflammatory macrophages primed with IFN-gamma. In contrast, BZ treatment of mice infected with drug-resistant T. cruzi population showed no effect whatsoever. The synthesis of IFN-gamma and RNI by splenocytes of mice infected with either susceptible and drug-resistant parasite populations, before and after treatment with BZ were also studied. On/v the splenocytes from mice infected with the drug-susceptible parasites treated with BZ produced high levels of IFN-gamma and RNI. Our findings indicate that BZ acts on the drug-susceptible T. cruzi parasites by enhancing the phagocytosis and the production of cytokines and RN!, thus, favouring the destruction of the intracellular parasites by the cellular compartment of the immune system.
... Ricardo T. Gazzinelli, Catherine Ropert, Igor C. Almeida, João S. Silva, and Marco A. Campos ... more ... Ricardo T. Gazzinelli, Catherine Ropert, Igor C. Almeida, João S. Silva, and Marco A. Campos ... 4. Gazzinelli RT, Wysocka M, Hayashi S, Denkers E, Hieny S, Caspar P, Trinchieri G, Sher A. Parasite Induced IL-12 stimulates early IFN-g synthesis and resistance during acute ...
The concept of pH-sensitive liposomes has been applied to the delivery of an oligonucleotide comp... more The concept of pH-sensitive liposomes has been applied to the delivery of an oligonucleotide complementary to the AUG region of the env mRNA of the Friend retrovirus. The oligonucleotide-containing liposomes were prepared by using the reverse phase evaporation or the freeze-thawing methodology. They were characterized for oligonucleotide entrapment efficiency, size, oligonucleotide release at different pH and stability. Optimisation of the
The Ras-Raf-MEK-ERK1/2 signaling pathway regulates fundamental processes in malignant cells. Howe... more The Ras-Raf-MEK-ERK1/2 signaling pathway regulates fundamental processes in malignant cells. However, the exact contributions of MEK1 and MEK2 to the development of cancer remain to be established. We studied the effects of MEK small-molecule inhibitors (PD98059 and U0126) and MEK1 and MEK2 knock-down on cell proliferation, apoptosis and MAPK activation. We showed a diminution of cell viability that was associated with a downregulation of cyclin D1 expression and an increase of apoptosis marker in MEK2 silenced cells; by contrast, a slight increase of cell survival was observed in the absence of MEK1 that correlated with an augment of cyclin D1 expression. These data indicate that MEK2 but not MEK1 is essential for MDA-MB-231 cell survival. Importantly, the role of MEK2 in cell survival appeared independent on ERK1/2 phosphorylation since its absence did not alter the level of activated ERK1/2. Indeed, we have reported an unrevealed link between MEK2 and MKK3/MKK6-p38 MAPK axis wher...
To stuck the effect of chemotherapy on parasite-macrophage interaction we used the wild-type Y st... more To stuck the effect of chemotherapy on parasite-macrophage interaction we used the wild-type Y strain (drug-susceptible) of Trypanosoma cruzi and a drug-resistant parasite population derived from the same strain. Trypomastigotes isolated from untreated infected mice, as well as, 3 h after treatment with BZ were incubated with inflammatory macrophages and used to study phagocytosis, parasite destruction, cytokine release and reactive nitrogen intermediates (RN!) synthesis. Phagocytosis and destruction of the drug-susceptible parasites were significant/v enhanced by drug treatment. These enhancements were accompanied by an increase in cytokines [interleukin (IL)-12 and tumour necrosis factor (TNF)alpha] and RNI release by murine inflammatory macrophages primed with IFN-gamma. In contrast, BZ treatment of mice infected with drug-resistant T. cruzi population showed no effect whatsoever. The synthesis of IFN-gamma and RNI by splenocytes of mice infected with either susceptible and drug-resistant parasite populations, before and after treatment with BZ were also studied. On/v the splenocytes from mice infected with the drug-susceptible parasites treated with BZ produced high levels of IFN-gamma and RNI. Our findings indicate that BZ acts on the drug-susceptible T. cruzi parasites by enhancing the phagocytosis and the production of cytokines and RN!, thus, favouring the destruction of the intracellular parasites by the cellular compartment of the immune system.
... Ricardo T. Gazzinelli, Catherine Ropert, Igor C. Almeida, João S. Silva, and Marco A. Campos ... more ... Ricardo T. Gazzinelli, Catherine Ropert, Igor C. Almeida, João S. Silva, and Marco A. Campos ... 4. Gazzinelli RT, Wysocka M, Hayashi S, Denkers E, Hieny S, Caspar P, Trinchieri G, Sher A. Parasite Induced IL-12 stimulates early IFN-g synthesis and resistance during acute ...
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